BACKGROUND At present,the conventional methods for diagnosing cerebral edema in clinical practice are computed tomography(CT)and magnetic resonance imaging(MRI),which can evaluate the location and degree of peripheral...BACKGROUND At present,the conventional methods for diagnosing cerebral edema in clinical practice are computed tomography(CT)and magnetic resonance imaging(MRI),which can evaluate the location and degree of peripheral cerebral edema,but cannot realize quantification.When patients have symptoms of diffuse cerebral edema or high cranial pressure,CT or MRI often suggests that cerebral edema is lagging and cannot be dynamically monitored in real time.Intracranial pressure monitoring is the gold standard,but it is an invasive operation with high cost and complications.For clinical purposes,the ideal cerebral edema monitoring should be non-invasive,real-time,bedside,and continuous dynamic monitoring.The dis-turbance coefficient(DC)was used in this study to dynamically monitor the occu-rrence,development,and evolution of cerebral edema in patients with cerebral hemorrhage in real time,and review head CT or MRI to evaluate the development of the disease and guide further treatment,so as to improve the prognosis of patients with cerebral hemorrhage.AIM To offer a promising new approach for non-invasive adjuvant therapy in cerebral edema treatment.METHODS A total of 160 patients with hypertensive cerebral hemorrhage admitted to the Department of Neurosurgery,Second Affiliated Hospital of Xi’an Medical University from September 2018 to September 2019 were recruited.The patients were randomly divided into a control group(n=80)and an experimental group(n=80).Patients in the control group received conventional empirical treatment,while those in the experimental group were treated with mannitol dehydration under the guidance of DC.Subsequently,we compared the two groups with regards to the total dosage of mannitol,the total course of treatment,the incidence of complications,and prognosis.RESULTS The mean daily consumption of mannitol,the total course of treatment,and the mean hospitalization days were 362.7±117.7 mL,14.8±5.2 days,and 29.4±7.9 in the control group and 283.1±93.6 mL,11.8±4.2 days,and 23.9±8.3 in the experimental group(P<0.05).In the control group,there were 20 patients with pulmonary infection(25%),30 with electrolyte disturbance(37.5%),20 with renal impairment(25%),and 16 with stress ulcer(20%).In the experimental group,pulmonary infection occurred in 18 patients(22.5%),electrolyte disturbance in 6(7.5%),renal impairment in 2(2.5%),and stress ulcers in 15(18.8%)(P<0.05).According to the Glasgow coma scale score 6 months after discharge,the prognosis of the control group was good in 20 patients(25%),fair in 26(32.5%),and poor in 34(42.5%);the prognosis of the experimental group was good in 32(40%),fair in 36(45%),and poor in 12(15%)(P<0.05).CONCLUSION Using DC for non-invasive dynamic monitoring of cerebral edema demonstrates considerable clinical potential.It reduces mannitol dosage,treatment duration,complication rates,and hospital stays,ultimately lowering hospital-ization costs.Additionally,it improves overall patient prognosis,offering a promising new approach for non-invasive adjuvant therapy in cerebral edema treatment.展开更多
Background:Traumatic cerebral edema(TCE)is a life-threatening condition caused by excessive fluid accumulation in the brain,leading to elevated intracranial pressure and potential brain damage.Current treatments,inclu...Background:Traumatic cerebral edema(TCE)is a life-threatening condition caused by excessive fluid accumulation in the brain,leading to elevated intracranial pressure and potential brain damage.Current treatments,including osmotic diuretics and antihypertensive medications,have limitations.Zhenwu Decoction,a traditional Chinese medicine formulation,has shown promise due to its multi-target pharmacological effects,including modulation of inflammation and regulation of aquaporins.Methods:Active components and targets of Zhenwu Decoction were identified using databases such as SymMap and TCMID.Protein-protein interaction networks and gene expression data related to toxic chemical exposure were analyzed through the GEO database and gene set enrichment analysis.Weighted gene co-expression network analysis(WGCNA)was used to identify TCE-associated gene modules.Molecular docking and in vivo validation using a traumatic brain injury model were conducted.Results:A total of 880 active components and 235 potential targets of Zhenwu Decoction were identified.Protein-protein interaction network analysis and WGCNA revealed key gene modules and inflammatory response-related DEGs.Molecular docking suggested lactiflorin and poricoic acid A as potential drug candidates targeting ATP2A2 and ATP2C1.Experimental results confirmed that Zhenwu Decoction improved TCE outcomes by upregulating these proteins.Conclusion:This study provides molecular evidence for the efficacy of Zhenwu Decoction in treating TCE,highlighting its mechanisms.The integration of WGCNA and molecular docking offers new insights into drug development and precision medicine for TCE.展开更多
Background:Spontaneous intracerebral hemorrhage(ICH)is a severe cerebrovascular disease with high mortality,frequently accompanied by cerebral edema and acute kidney injury(AKI).Current treatment options remain limite...Background:Spontaneous intracerebral hemorrhage(ICH)is a severe cerebrovascular disease with high mortality,frequently accompanied by cerebral edema and acute kidney injury(AKI).Current treatment options remain limited.Methods:Active components and potential targets of Zhenwu Decoction(ZWD)were identified using multi-database screening.Protein-protein interaction(PPI)networks were constructed,and differentially expressed genes(DEGs)were analyzed using GEO datasets.Molecular docking and bioinformatics tools identified interactions between ZWD components and key targets,particularly AQP4 and AVPR1.Animal and cellular experiments validated the effects of ZWD on inflammation,oxidative stress,and apoptosis.Results:ZWD demonstrated significant modulation of AQP4 and AVPR1 expression,improving cerebral edema and renal function.Molecular docking confirmed ZWD’s active compounds interact strongly with these targets.In vivo studies revealed ZWD reduced oxidative stress and inflammatory responses,while in vitro experiments confirmed AVPR1’s role in apoptosis and inflammation,with ZWD significantly mitigating these adverse effects.Conclusion:This study is the first to demonstrate that ZWD alleviates cerebral edema following ICH by targeting AQP4 and AVPR1,offering new therapeutic insights for ICH management.展开更多
Cerebral edema is characterized by fluid accumulation,and the glymphatic system(GS)plays a pivotal role in regulating fluid transport.Using the Tenecteplase system,magnesium salt of salvianolic acid B/ginsenoside Rg1(...Cerebral edema is characterized by fluid accumulation,and the glymphatic system(GS)plays a pivotal role in regulating fluid transport.Using the Tenecteplase system,magnesium salt of salvianolic acid B/ginsenoside Rg1(SalB/Rg1)was injected intravenously into mice 4.5 h after middle cerebral artery occlusion and once every 24 h for the following 72 h.GS function was assessed by Evans blue imaging,near-infrared fluorescence region II(NIR-II)imaging,and magnetic resonance imaging(MRI).SalB/Rg1 had significant effects on reducing the infarct volume and hemorrhagic transformation score,improving neurobehavioral function,and protecting tissue structure,especially inhibiting cerebral edema.Meanwhile,the influx/efflux drainage of GS was enhanced by SalB/Rg1 according to NIR-II imaging and MRI.SalB/Rg1 inhibited matrix metalloproteinase-9(MMP-9)activity,reduced cleavedβ-dystroglycan(β-DG),and stabilized aquaporin-4(AQP4)polarity,which was verified by colocalization with CD31.Our findings indicated that SalB/Rg1 treatment enhances GS function and attenuates cerebral edema,accompanying the regulation of the MMP9/β-DG/AQP4 pathway.展开更多
The anti-inflammatory and antioxidant effects of exendin-4（Ex-4） have been reported previously.However,whether（Ex-4） has anti-inflammatory and antioxidant effects on high-altitude cerebral edema（HACE） remains po...The anti-inflammatory and antioxidant effects of exendin-4（Ex-4） have been reported previously.However,whether（Ex-4） has anti-inflammatory and antioxidant effects on high-altitude cerebral edema（HACE） remains poorly understood.In this study,two rat models of HACE were established by placing rats in a hypoxic environment with a simulated altitude of either 6000-or 7000-m above sea level（MASL） for 72 hours.An altitude of 7000 MASL with 72-hours of hypoxia was found to be the optimized experimental paradigm for establishing HACE models.Then,in rats where a model of HACE was established by introducing them to a 7000 MASL environment with 72-hours of hypoxia treatment,2,10 and,100 μg of Ex-4 was intraperitoneally administrated.The open field test and tail suspension test were used to test animal behavior.Routine methods were used to detect change in inflammatory cells.Hematoxylin-eosin staining was performed to determine pathological changes to brain tissue.Wet/dry weight ratios were used to measure brain water content.Evans blue leakage was used to determine blood-brain barrier integrity.Enzyme-linked immunosorbent assay（ELISA） was performed to measure markers of inflammation and oxidative stress including superoxide dismutase,glutathione,and malonaldehyde values,as well as interleukin-6,tumor necrosis factor-alpha,cyclic adenosine monophosphate levels in the brain tissue.Western blot analysis was performed to determine the levels of occludin,ZO-1,SOCS-3,vascular endothelial growth factor,EPAC1,nuclear factor-kappa B,and aquaporin-4.Our results demonstrate that Ex-4 preconditioning decreased brain water content,inhibited inflammation and oxidative stress,alleviated brain tissue injury,maintain blood-brain barrier integrity,and effectively improved motor function in rat models of HACE.These findings suggest that Ex-4 exhibits therapeutic potential in the treatment of HACE.展开更多
Previous investigations suggest that ataxia is common and often one of the most reliable warning signs of high altitude cerebral edema(HACE). The aim of this study was to investigate the diagnostic role of ataxia in a...Previous investigations suggest that ataxia is common and often one of the most reliable warning signs of high altitude cerebral edema(HACE). The aim of this study was to investigate the diagnostic role of ataxia in acute mountain sickness(AMS)and HACE among mountain rescuers on the quake areas,and in approaching the relation between AMS and HACE. After the earthquake on April 14,2010,approximately 24 080 lowland rescuers were rapidly transported from sea level or lowlands to the mountainous rescue sites at 3 750 ~ 4 568 m,and extremely hardly worked for an emergency treatment after arrival. Assessments of acute altitude illness on the quake areas were using the Lake Louise Scoring System. 73 % of the rescuers were found to be developed AMS. The incidence of high altitude pulmonary edema(HAPE)and HACE was 0.73 % and 0.26 %,respectively,on the second to third day at altitude. Ataxia sign was measured by simple tests of coordination including a modified Romberg test. The clinical features of 62 patients with HACE were analyzed. It was found that the most frequent,serious neurological symptoms and signs were altered mental status(50/62,80.6 %)and truncal ataxia(47/62,75.8 %). Mental status change was rated slightly higher than ataxia,but ataxia occurred earlier than mental status change and other symptoms. The earliest sign of ataxia was a vague unsteadiness of gait,which may be present alone in association with or without AMS. Advanced ataxia was correlated with the AMS scores,but mild ataxia did not correlate with AMS scores at altitudes of 3 750~4 568 m. Of them,14 patients were further examined by computerized tomographic scanning of the brain and cerebral magnetic resonance imagines were examined in another 15 cases. These imaging studies indicated that the presence of the cerebral edema was in 97 % of cases who were clinically diagnosed as HACE(28/29). Ataxia seems to be a reliable sign of advanced AMS or HACE,so does altered mental status.展开更多
Vitamin K antagonists, such as warfarin and phen-procoumon, are the first-line oral anticoagulants for primary and secondary prevention of cerebral embo-lism in patients with atrial fibrillation. Although vitamin K an...Vitamin K antagonists, such as warfarin and phen-procoumon, are the first-line oral anticoagulants for primary and secondary prevention of cerebral embo-lism in patients with atrial fibrillation. Although vitamin K antagonists can significantly decrease the risk of stroke, their use is limited by several important drawbacks, such as a narrow therapeutic window, the risk of intracranial and gastrointestinal bleeding, interactions with a number of drugs and nutrients, and the need for regular laboratory tests for therapy adjustment. Currently, new oral anticoagulants, such as direct thrombin inhibitors (e.g., dabigatran) and direct factor Xa inhibitors (e.g., apixaban, rivaroxaban), are being developed and tested in clinical trials. Dabigatran and rivaroxaban were recently approved for prevention of cerebral embolism in patients with atrial fibrillation. The ad-vantages of dabigatran in comparison to warfarin are a lower rate of major bleedings with dabigatran 110mg bid, a better efficacy with dabigatran 150mg bid, no clinically relevant interactions with other drugs and no need for routine coagulation monitoring. The disadvantages are the absence of antidote and the absence of routine laboratory tests for precise mea-surements of anticoagulant effect of direct thrombin/ factor Xa inhibitors. This review will focus on throm-bin and factor Xa inhibitors, which are new and promising oral anticoagulants for the prevention of cerebral embolism. We will discuss their pharmacol-ogical and clinical properties and provide the most recent updates on their clinical trials.展开更多
The aim of this study was to investigate the possible beneficial role of telmisartan in cerebral edema after traumatic brain injury（TBI） and the potential mechanisms related to the nucleotide-binding oligomerization...The aim of this study was to investigate the possible beneficial role of telmisartan in cerebral edema after traumatic brain injury（TBI） and the potential mechanisms related to the nucleotide-binding oligomerization domain（NOD）-like receptor（NLR） pyrin domain-containing 3（NLRP3） inflammasome activation. TBI model was established by cold-induced brain injury. Male C57BL/6 mice were randomly assigned into 3, 6, 12, 24, 48 and 72 h survival groups to investigate cerebral edema development with time and received 0, 5, 10, 20 and 40 mg/kg telmisartan by oral gavage, 1 h prior to TBI to determine the efficient anti-edemic dose. The therapeutic window was identified by post-treating 30 min, 1 h, 2 h and 4 h after TBI. Blood-brain barrier（BBB） integrity, the neurological function and histological injury were assessed, at the same time, the m RNA and protein expression levels of NLRP3 inflammasome, IL-1β and IL-18 concentrations in peri-contused brain tissue were measured 24 h post TBI. The results showed that the traumatic cerebral edema occurred from 6 h, reached the peak at 24 h and recovered to the baseline 72 h after TBI. A single oral dose of 5, 10 and 20 mg/kg telmisartan could reduce cerebral edema. Post-treatment up to 2 h effectively limited the edema development. Furthermore, prophylactic administration of telmisartan markedly inhibited BBB impairment, NLRP3, apoptotic speck-containing protein（ASC） and Caspase-1 activation, as well as IL-1β and IL-18 maturation, subsequently improved the neurological outcomes. In conclusion, telmisartan can reduce traumatic cerebral edema by inhibiting the NLRP3 inflammasome-regulated IL-1β and IL-18 accumulation.展开更多
The present study investigated the effects of the mitochondrial calcium uniporter inhibitor ruthenium red and the agonist spermine on cerebral edema in rats with cerebral ischemia reperfusion injury. Left middle cereb...The present study investigated the effects of the mitochondrial calcium uniporter inhibitor ruthenium red and the agonist spermine on cerebral edema in rats with cerebral ischemia reperfusion injury. Left middle cerebral artery occlusion （MCAO） was induced in rats using the suture method. Following 24 hours of ischemic reperfusion, neurological function scores of rats with MCAO, and rats pretreated with ruthenium red and spermine were significantly lower, however, water content of brain tissue, aquaporin 4 expression and immunoglobulin G （IgG） exudation were significantly higher than those of sham-operated rats. Compared with MCAO rats and spermine-treated rats, neurological function scores were considerably higher, and brain tissue water content, aquaporin 4 expression and IgG exudation decreased in ruthenium red-treated rats. These findings suggest that preventive application of the mitochondrial calcium uniporter inhibitor ruthenium red can significantly decrease aquaporin 4 and IgG expression, influence the permeability of the blood brain barrier, and thereby decrease the extent of cerebral edema.展开更多
BACKGROUND:Aquaporin-4(AQP-4),which is able to rapidly transport water within the brain,is highly expressed in brain tissue.It also plays an important role in the formation of cerebral edema following brain injury.How...BACKGROUND:Aquaporin-4(AQP-4),which is able to rapidly transport water within the brain,is highly expressed in brain tissue.It also plays an important role in the formation of cerebral edema following brain injury.However,the role of AQP-4 in the formation of cerebral edema following severe bums remains unknown.OBJECTIVE:To study changes in AQP-4 protein and mRNA expression during formation of cerebral edema following severe burns,and to explore the correlation between AQP-4 protein and mRNA expression with plasma levels of arginine vasopressin(AVP).DESIGN,TIME AND SETTING:A randomized,controlled,animal experiment was performed at the Research Center of Neuroscience,Chongqing Medical University from 2007 to 2008.MATERIALS:Biotin-labeled goat anti-rabbit antibody was provided by Beijing Zhongshan Biotechnology,China;in situ hybridization kit was provided by Wuhan Boster Biotechnology,China;rabbit anti-AQP-4 polyclonal antibody and horseradish peroxidase-labeled goat anti-rabbit IgG were provided by Chemicon,USA;AVP radioimmunoassay kit was provided by the Research Department of Neurobiology,the Second Military Medical University of Shanghai,China.METHODS:A total of 180 adult,healthy,Wistar rats were randomly assigned to control and burn groups with 30 rats in each group.The burn group was observed at five different time points:2,6,12,24,and 48 hours after burn.Hair on the mouse back was removed to expose skin on the back.After 1 day,skin with the hair removed was dipped into 100℃water for 15 seconds to induce grade III bum injury that measures 30%of total bum surface area.MAIN OUTCOME MEASURES:Brain water content was measured using the dry-wet weight method.AQP-4 protein and mRNA expressions were detected using immunohistochemistry,in situ hybridization,Western blot,and reverse transcription-polymerase chain reaction;dynamic changes in plasma AVP were detected using radioimmunoassay.RESULTS:Brain water content gradually increased following severe burn injury.AQP-4 protein and mRNA expressions were upregulated in the supraoptic nucleus,suprachiasmatic nucleus,paraventricular nucleus,hippocampus,choroid plexus,and cerebral cortex.Plasma AVP levels increased following burn injury.AQP-4 protein and mRNA expressions positively correlated with brain water content and AVP levels during formation of cerebral edema(r=0.870,0.848,P〈0.01).CONCLUSION:AQP-4 participated in the formation of cerebral edema following burn injury.Plasma AVP upregulated AQP-4 expression in brain tissue,thereby promoting formation of cerebral edema.展开更多
Objective:To observe the effect of glycerol fructose combined with mannitol in the treatment of patients with clinical intracerebral hemorrhage complicated by cerebral edema and increased intracranial pressure,and to ...Objective:To observe the effect of glycerol fructose combined with mannitol in the treatment of patients with clinical intracerebral hemorrhage complicated by cerebral edema and increased intracranial pressure,and to evaluate the clinical application value of this treatment.Methods:Seventy patients with cerebral hemorrhage complicated by brain edema were randomly divided into observation and control groups.Both groups had exactly the same number of study participants.There were some differences in specific treatment methods.The specific process is as follows:The control group was treated with mannitol,while the observation group was treated with dual-purpose glycerol fructose.Several important indicators after treatment in the two groups were scored,the effects between different groups were compared,and the effect of clinical treatment was evaluated.Results:The final effect was compared and analyzed.After data analysis,we found that the intracranial pressure of the observation group was lower,the volume of brain edema was significantly reduced(P<0.05),and the NIH Stroke Scale/Score(NIHSS)was lower(P<0.05).Conclusion:Using mannitol combined with glycerol fructose can achieve better treatment effect by significantly improving the problem of brain edema.展开更多
Objectives Over-hydration in diabetic ketoacidosis(DKA) may increase the risk of cerebral edema in children.Methods We have organized a prospective descriptive cohort study of 38pediatric patients aged 1month to 14yea...Objectives Over-hydration in diabetic ketoacidosis(DKA) may increase the risk of cerebral edema in children.Methods We have organized a prospective descriptive cohort study of 38pediatric patients aged 1month to 14years,who were diagnosed with DKA with 41episodes of diabetic ketoacidosis,presented to the pediatric emergency department at the First Affiliated Hospital of Xinjiang Medical University from January 2010to February 2012.This study was approved by the Ethics Committee of The First Affiliated Hospital of Xinjiang Medical University.Results The magnitude presentation of the percentile 25%-70% was in the ratio of 5.6%(3.4%-8.2%)(6.1±4).So there was no clinical and biochemical assessment variation needed.These both of the variations,all of the diabetic ketoacidosis patient approached.Further all the patient variations were not correlated with the amplitude of variation and magnitude presentation and did not affect the fluid concentration and the quantity of the fluid was 47.8mL / kg(36.556.3) in the first 12hours.Conclusion For the conclusion of the exact parameters and the magnitude variations of the fluid in the patients of diabetic ketoacidosis,all of the conformations need study on the larger scale.展开更多
High grade gliomas are the commonest intrinsic brain tumours and account for more average years of life lost than all the common cancers. It has become the commonest cause of cancer death in men under the age of 45 an...High grade gliomas are the commonest intrinsic brain tumours and account for more average years of life lost than all the common cancers. It has become the commonest cause of cancer death in men under the age of 45 and women under the age of 35. Although surgical resection can greatly reduce tumour bulk, complete excision is virtually impossible due to the infiltrative nature of these tumours. In an attempt to treat the infiltrating tumour cells, there has been much interest in using local therapies inserted at the time of surgery. The authors report a case of fatal cerebral edema unresponsive to aggressive medical and surgical assessment that finally evolved to premature death in the early postsurgical period, after the craniotomy and implantation of Gliadel wafers. They note that high doses of dexamethasone were insufficient to prevent cerebral edema and death. A search for corticosteroid use and dosing for patients treated with Gliadel wafers in the published literature revealed no recommendations on the doses of steroids to be administered. In our opinion this is a very important issue and maybe the key point for the treatment of this disease, and may need to be addressed with treatment guidelines in the near future in order to ensure better results on patient’s survival. Prior to this case review there had been two similar report but a later presentation. So we think that this is the first case report of acute fulminant cerebral edema secondary to gliadel wafers in the early period.展开更多
BACKGROUND: It has shown that magnetic field can improve blood circulation, decrease blood viscosity, inhibit free radicals, affect Ca2+ flow in nerve cells, control inflammatory and immunological reaction, and accele...BACKGROUND: It has shown that magnetic field can improve blood circulation, decrease blood viscosity, inhibit free radicals, affect Ca2+ flow in nerve cells, control inflammatory and immunological reaction, and accelerate nerve cell regeneration. In addition, protective effect of magnetic field, which acts as an iatrophysics, on ischemic brain tissues has been understood gradually. OBJECTIVE: To investigate the effects of rotating magnetic field (RMF) on volume of cerebral infarction, cerebral edema and metabolism of free radicals in rats after cerebral ischemia/reperfusion injury. DESIGN: Randomized controlled animal study. SETTING: Rehabilitation Center of disabled children, Liaoniang; Department of Rehabilitation, the Second Affiliated Hospital, China Medical University; Department of Rehabilitation Physiotherapy, the First Affiliated Hospital, China Medical University. MATERIALS: A total of 70 healthy Wistar rats aged 18-20 weeks of both genders were selected and randomly divided into 3 groups: sham operation group with 12 rats, control group with 20 rats and treatment group with 38 rats. The treatment group included 4 time points: immediate reperfusion with 6 ones, 6-hour reperfusion with 20 ones, 12-hour reperfusion with 6 ones and 18-hour reperfusion with 6 rats. Main instruments were detailed as follows: magnetic head of rotating magnetic device was 6 cm in diameter; magnetic induction intensity at the surface of magnetic head was 0.25 T in silence; the maximal magnetic induction intensity was 0.09 T at the phase of rotation; the average rotating speed was 2500 r per minute. METHODS: The experiment was carried out in the China Medical University in March 2003. Focal cerebral ischemic animal models were established with modified Longa’s method. Operation was the same in the sham operation, but the thread was inserted as 10 mm. Neurologic impairment was assessed with 5-rating method to screen out cases. Those survivals with grade 1 and grade 2 after ischemia for 2 hours and reperfusion for 24 hours were included in the control group and treatment group. Those in the sham operation group and control group were not treated with RMF. Magnetic head was directed towards the head of rats of the treatment group, and the magnetic head was about 7 mm from skin, treated for 15 minutes. The rats were decapitated to take out brains at 24 hours after reperfusion in each group. Water content of brain and volume of cerebral infarction were assessed with wet-dry weight method and TTC staining, respectively. Activity of superoxide dismutase (SOD), content of malondialdehyde (MDA) and change of brain histomorphology in brain tissue of ischemic side were analyzed. MAIN OUTCOME MEASURES: ① Volume of cerebral infarction and changes of water content in brain; ② measurements of SOD and MDA contents in brain tissue of rats in all groups. RESULTS: A total of 70 qualified animals were involved in the final analysis after rejecting the death and unqualified animal models. ① Water content of brain: Water content of brain in the treatment was less than that in the control group at any time point except the immediate time point, and cerebral edema was relieved [(2.48±0.22)%, (2.32±0.19)%, (2.23±0.36)%, (2.91±0.44)%, P < 0.05]. In addition, there were no significant differences among 6-hour, 12-hour and 18-hour reperfusion groups (P > 0.05). ② Volume of cerebral infarction: The absolute volume of cerebral infarction in the treatment group was smaller than that in the control group [(128.21±15.05), (171.22±40.50) mm3, t =2.438, P < 0.05], and the relative volume of cerebral infarction was smaller than that in the control group [(20.22±1.44)%, (25.17±3.85)%, t =2.95, P < 0.05]. ③ Contents of SOD and MDA in brain tissues: Compared with the control group, the SOD content in the brain tissue in the treatment group increased [(54.54±3.85), (69.52±5.88) kNU/g, t =5.568, P < 0.05], while the MDA content decreased [(0.85±0.06), (1.03±0.09) μmol/g, t =4.076, P < 0.05]. ④ General morphological observation: General morphology manifested that the edema was distinct in the right cerebral hemisphere in the control group, showing fat-like white, shallow anfractuosity, flat gyria, brittle tissue and easy to break up. The edema of right cerebral hemisphere was light and surface was hyperaemia in the treatment group. CONCLUSION: RMF may improve anti-oxidative ability of brain tissue of rats with acute focal cerebral ischemia/reperfusion injury and reduce volume of cerebral infarction and degrees of cerebral edema.展开更多
Objective:To study the relationship of cerebral edema with apoptosis, inflammatory factor generation and AQPs expression in the rat model with closed craniocerebral injury.Methods:Male SD rats were selected as experim...Objective:To study the relationship of cerebral edema with apoptosis, inflammatory factor generation and AQPs expression in the rat model with closed craniocerebral injury.Methods:Male SD rats were selected as experimental animals and divided into model group and control group. Model group were established into the closed craniocerebral injury models and control group received sham operation. The water content of damaged brain tissue as well as the expression of apoptosis molecules, the generation of inflammatory factors and the expression of aquaporins (AQPs) molecules were measured 7 d after model establishment.Results:The water content of brain tissue of model group was significantly higher than that of control group;Homer1a, Pim-3, Bcl-2, AQP1, AQP4 and AQP9 mRNA expression in brain tissue of model group were significantly lower than those of control group while Cdk5, FasL and Caspase-3 mRNA expression as well as NF-kB, TNF-α, IL-1β, IL-6 and p-JNK generation were significantly higher than those of control group. Homer1a, Pim-3, Bcl-2, AQP1, AQP4 and AQP9 mRNA expression in brain tissue of model group were negatively correlated with water content while Cdk5, FasL and Caspase-3 mRNA expression as well as NF-kB, TNF-α, IL-1β, IL-6 and p-JNK generation were positively correlated with water content.Conclusion:The excessive apoptosis, increased inflammatory factor generation and decreased AQPs expression are closely related to the occurrence of cerebral edema in the process of closed craniocerebral injury.展开更多
Objective To investigate the expression of cytochrome C in perihematomal brain tissue and its relationship with the histopathological change and formation of cerebral edema in patients with hypertensive cerebral hemor...Objective To investigate the expression of cytochrome C in perihematomal brain tissue and its relationship with the histopathological change and formation of cerebral edema in patients with hypertensive cerebral hemorrhage.Methods Thirty four patients(23 male,11 female) of hypertensive cerebral hemorrhage in hospital from Sep.2001 to Sep.2002 were selected with a mean age 55.6± 10.2 years(from 35 to 75 years).The mean volume of hemorrhagic blood was 50.4±11.6 ml(from 25 to 85 ml).The perihematomal brain tissue was obtained from the minimally invasive surgery.Histopathological change and expressions of cytochrome C in perihematomal brain tissue was detected by histopathological and immunohistochemical techniques.The volume of perihematomal cerebral edema was determined by computed tomographic scan before operation.The results of staining and the volume of perihematomal cerebral edema were analyzed with double blind fashion.Results Perihematomal cerebral edema were found 12-72h after cerebral hemorrhage.Myelin sheath degeneration,condensation of nucleus and typical apopototic body were observed in perihematomal brain tissue.Expression of cytochrome C in perihematomal brain tissue was observed at 4 h and reached peak around 48-72 h after cerebral hemorrhage.Cytochrome C expressed higher positively in 16 patients and lower positively in 13 patients.Cytochrome C expression was not detected only in 5 patints.There were significant differences in volume of perihematomal cerebral edema with different expression of cytochrome C in perihematomal brain tissue(P<0.01).Conclusions Cytochrome C expression was upregulated in perihematomal brain tissue in patients with hypertensive cerebral hemorrhage.Cytochrome C might involve in the histopathological change and the formation of perihematomal cerebral展开更多
This study sought to elucidate the genetic correlation of cerebral venous sinus thrombosis caused by a hereditary antithrombin deficiency in a Chinese family, at the genetic and protein levels. A nonsense mutation fro...This study sought to elucidate the genetic correlation of cerebral venous sinus thrombosis caused by a hereditary antithrombin deficiency in a Chinese family, at the genetic and protein levels. A nonsense mutation from C to T on locus 6431 in exon 3B of the antithrombin gene was observed, leading to an arginine （CGA） to stop codon （TGA） change in the protein. This is the first report of this mutation in China. Ineffective heparin therapy in the propositus patient is associated with a lack of heparin binding sites after antithrombin gene mutation. Characteristic low intracranial pressure in the acute phase might be specific to this patient with cerebral venous sinus thrombosis.展开更多
Vasogenic edema,caused by the disruption of the blood-brain barrier(BBB),is a significant pathological factor in high-altitude cerebral edema(HACE).Due to the rapid progression and high mortality rate of HACE,prophy-l...Vasogenic edema,caused by the disruption of the blood-brain barrier(BBB),is a significant pathological factor in high-altitude cerebral edema(HACE).Due to the rapid progression and high mortality rate of HACE,prophy-lactic treatment is important.Mesenchymal stem cell exosomes(MSC-EXO)are increasingly being used in tissue injury repair,and research suggests that appropriate conditioning can enhance the targeted efficacy of exosome therapy.Our in vitro experiments revealed that hypoxia preconditioned MSC-EXO(H-EXO)significantly out-performed normoxic MSC-EXO(N-EXO)in multiple protective aspects.Specifically,H-EXO demonstrated enhanced capacity to mitigate hypoxia-induced aberrant angiogenesis,maintain vascular endothelial cell viability,and suppress ROS accumulation and apoptotic signaling under hypoxic stress.Mechanistic investiga-tion identified miR-125a-5p cargo in H-EXO as a key mediator of RTEF-1 targeted inhibition during hypoxic exposure.In corresponding in vivo studies,H-EXO administration effectively attenuated HACE-induced patho-logical angiogenesis while maintaining crucial vascular homeostasis markers.The therapeutic effects manifested through three principal aspects:1)downregulation of RTEF-1/VEGF hyperexpression,2)modulation of VEcadherin,SMA,and PDGFRα+βexpression to preserve BBB integrity,and 3)concurrent protection of neuro-vascular functions against HACE-induced damage.This investigation elucidates the miR-125a-5p/RTEF-1 axis as the central mechanism through which hypoxic preconditioning enhances MSC-EXO’s endothelial protective properties.Our findings establish H-EXO’s multimodal therapeutic potential,demonstrating its capacity to simultaneously inhibit pathological angiogenesis,restore BBB function,and protect neural tissue under hypoxic stress conditions.The study elucidates key mechanisms underlying clinical prevention and management of HACE by delineating H-EXO’s preventive mechanisms against hypoxia-induced cerebrovascular injury.展开更多
High-altitude cerebral edema(HACE)is a potentially fatal encephalopathy associated with a time-dependent exposure to the hypobaric hypoxia of altitude.The formation of HACE is affected by both vasogenic and cytotoxic ...High-altitude cerebral edema(HACE)is a potentially fatal encephalopathy associated with a time-dependent exposure to the hypobaric hypoxia of altitude.The formation of HACE is affected by both vasogenic and cytotoxic edema.The over-activated microglia potentiate the damage of blood-brain barrier(BBB)and exacerbate cytotoxic edema.In light with the activation of microglia in HACE,we aimed to investigate whether the over-activated microglia were the key turning point of acute mountain sickness to HACE.In in vivo experiments,by exposing mice to hypobaric hypoxia(7000 m above sea level)to induce HACE model,we found that microglia were activated and migrated to blood vessels.Microglia depletion by PLX5622 obviously relieved brain edema.In in vitro experiments,we found that hypoxia induced cultured microglial activation,leading to the destruction of endothelial tight junction and astrocyte swelling.Up-regulated nuclear respiratory factor 1(NRF1)accelerated pro-inflammatory factors through transcriptional regulation on nuclearfactorkappa B p65(NF-kB p65)and mitochondrial transcription factorA(TFAM)in activated microglia under hypoxia.NRF1 also up-regulated phagocytosis by transcriptional regulation on caveolin-1(CAV-1)and adaptorrelated protein complex 2 subunit beta(AP2B1).The present study reveals a new mechanism in HACE:hypoxia over-activates microglia through up-regulation of NRF1,which both induces inflammatory response through transcriptionally activating NF-kB p65 and TFAM,and enhances phagocytic function through up-regulation of CAV-1 and AP2B1;hypoxia-activatedmicroglia destroy the integrity of BBB and release pro-inflammatory factors that eventually induce HACE.展开更多
Background Acute high-altitude illness(AHAI)refers to a series of syndromes including acute mountain sickness(AMS),high-altitude pulmonary edema(HAPE)and high-altitude cerebral edema(HACE).Among these,HACE is a severe...Background Acute high-altitude illness(AHAI)refers to a series of syndromes including acute mountain sickness(AMS),high-altitude pulmonary edema(HAPE)and high-altitude cerebral edema(HACE).Among these,HACE is a severe and potentially life-threatening condition that can occur when individuals ascend to high altitudes.It is often characterized by ataxia,confusion,and altered mental status.Without appropriate treatment,HACE can rapidly progress to coma,but seizures are infrequent in occurrence.Case presentation Here,we report a severe HACE patient with coma and status epilepticus.The patient is a 23-year-old male who was visiting Lhasa for the first time.He initially experienced headaches and dizziness on the first day,and then he was found in coma with limb convulsions on the next day.Immediate medical attention was sought,and brain CT and MRI scans showed reversible white matter lesions,especially in the corpus callosum and subcortical white matter.Although the lesions disappeared on T1 and T2 sequences,microbleeds were observed on the SWI sequence.After treatment with tracheal intubation,glucocorticoids and hyperbaric oxygen,the cerebral edema has resolved and the clinical symptoms improved,the patient has no seizures anymore.Conclusions HACE typically follows AMS and poses a significant risk to life.Clinical manifestations mainly include ataxia,alterations of behavior,and impaired consciousness,with severe cases progressing to coma.Seizures,though rarely observed,may occur.Imaging shows reversible white matter lesions,with microbleeds being a significant and persistent imaging marker over time.Administration of glucocorticoids plays a crucial role in treatment.Despite experiencing seizures,this patient did not experienced any further episodes once his condition improved.展开更多
基金Supported by the Shaanxi Provincial Key Research and Development Plan Project,No.2020ZDLSF01-02.
文摘BACKGROUND At present,the conventional methods for diagnosing cerebral edema in clinical practice are computed tomography(CT)and magnetic resonance imaging(MRI),which can evaluate the location and degree of peripheral cerebral edema,but cannot realize quantification.When patients have symptoms of diffuse cerebral edema or high cranial pressure,CT or MRI often suggests that cerebral edema is lagging and cannot be dynamically monitored in real time.Intracranial pressure monitoring is the gold standard,but it is an invasive operation with high cost and complications.For clinical purposes,the ideal cerebral edema monitoring should be non-invasive,real-time,bedside,and continuous dynamic monitoring.The dis-turbance coefficient(DC)was used in this study to dynamically monitor the occu-rrence,development,and evolution of cerebral edema in patients with cerebral hemorrhage in real time,and review head CT or MRI to evaluate the development of the disease and guide further treatment,so as to improve the prognosis of patients with cerebral hemorrhage.AIM To offer a promising new approach for non-invasive adjuvant therapy in cerebral edema treatment.METHODS A total of 160 patients with hypertensive cerebral hemorrhage admitted to the Department of Neurosurgery,Second Affiliated Hospital of Xi’an Medical University from September 2018 to September 2019 were recruited.The patients were randomly divided into a control group(n=80)and an experimental group(n=80).Patients in the control group received conventional empirical treatment,while those in the experimental group were treated with mannitol dehydration under the guidance of DC.Subsequently,we compared the two groups with regards to the total dosage of mannitol,the total course of treatment,the incidence of complications,and prognosis.RESULTS The mean daily consumption of mannitol,the total course of treatment,and the mean hospitalization days were 362.7±117.7 mL,14.8±5.2 days,and 29.4±7.9 in the control group and 283.1±93.6 mL,11.8±4.2 days,and 23.9±8.3 in the experimental group(P<0.05).In the control group,there were 20 patients with pulmonary infection(25%),30 with electrolyte disturbance(37.5%),20 with renal impairment(25%),and 16 with stress ulcer(20%).In the experimental group,pulmonary infection occurred in 18 patients(22.5%),electrolyte disturbance in 6(7.5%),renal impairment in 2(2.5%),and stress ulcers in 15(18.8%)(P<0.05).According to the Glasgow coma scale score 6 months after discharge,the prognosis of the control group was good in 20 patients(25%),fair in 26(32.5%),and poor in 34(42.5%);the prognosis of the experimental group was good in 32(40%),fair in 36(45%),and poor in 12(15%)(P<0.05).CONCLUSION Using DC for non-invasive dynamic monitoring of cerebral edema demonstrates considerable clinical potential.It reduces mannitol dosage,treatment duration,complication rates,and hospital stays,ultimately lowering hospital-ization costs.Additionally,it improves overall patient prognosis,offering a promising new approach for non-invasive adjuvant therapy in cerebral edema treatment.
基金the financial support provided by the Discipline Construction Project of Shanghai Pudong New Area Health Commission(Grant Number:PWZzb2022-21)the Shanghai Pudong New Area Health System Discipline Leader Training Project(Grant Number:PWRd2022-14)+1 种基金the Health Science and Technology Project of Shanghai Pudong New Area Health Committee(Grant Number:PW2023A-51)the Shanghai Pudong New Area Gongli Hospital Youth Fund Project(Grant Number:2020YQNJJ-16).
文摘Background:Traumatic cerebral edema(TCE)is a life-threatening condition caused by excessive fluid accumulation in the brain,leading to elevated intracranial pressure and potential brain damage.Current treatments,including osmotic diuretics and antihypertensive medications,have limitations.Zhenwu Decoction,a traditional Chinese medicine formulation,has shown promise due to its multi-target pharmacological effects,including modulation of inflammation and regulation of aquaporins.Methods:Active components and targets of Zhenwu Decoction were identified using databases such as SymMap and TCMID.Protein-protein interaction networks and gene expression data related to toxic chemical exposure were analyzed through the GEO database and gene set enrichment analysis.Weighted gene co-expression network analysis(WGCNA)was used to identify TCE-associated gene modules.Molecular docking and in vivo validation using a traumatic brain injury model were conducted.Results:A total of 880 active components and 235 potential targets of Zhenwu Decoction were identified.Protein-protein interaction network analysis and WGCNA revealed key gene modules and inflammatory response-related DEGs.Molecular docking suggested lactiflorin and poricoic acid A as potential drug candidates targeting ATP2A2 and ATP2C1.Experimental results confirmed that Zhenwu Decoction improved TCE outcomes by upregulating these proteins.Conclusion:This study provides molecular evidence for the efficacy of Zhenwu Decoction in treating TCE,highlighting its mechanisms.The integration of WGCNA and molecular docking offers new insights into drug development and precision medicine for TCE.
基金support from the Medical Discipline Construction Program of Shanghai Pudong New Area Health Commission(the Specialty Program)(Grant Number:PWZzb2022-21)The Academic Leaders Training Program of Shanghai Pudong New Area Health Commission(Grant Number:PWRd2022-14)+1 种基金The Scientific Research Program of Shanghai Pudong New Area Health Commission(the Achievement Transformation Program)(Grant Number:PW2023A-51)the Shanghai Pudong New Area Gongli Hospital Youth Fund Project(Grant Number:2020YQNJJ-16).
文摘Background:Spontaneous intracerebral hemorrhage(ICH)is a severe cerebrovascular disease with high mortality,frequently accompanied by cerebral edema and acute kidney injury(AKI).Current treatment options remain limited.Methods:Active components and potential targets of Zhenwu Decoction(ZWD)were identified using multi-database screening.Protein-protein interaction(PPI)networks were constructed,and differentially expressed genes(DEGs)were analyzed using GEO datasets.Molecular docking and bioinformatics tools identified interactions between ZWD components and key targets,particularly AQP4 and AVPR1.Animal and cellular experiments validated the effects of ZWD on inflammation,oxidative stress,and apoptosis.Results:ZWD demonstrated significant modulation of AQP4 and AVPR1 expression,improving cerebral edema and renal function.Molecular docking confirmed ZWD’s active compounds interact strongly with these targets.In vivo studies revealed ZWD reduced oxidative stress and inflammatory responses,while in vitro experiments confirmed AVPR1’s role in apoptosis and inflammation,with ZWD significantly mitigating these adverse effects.Conclusion:This study is the first to demonstrate that ZWD alleviates cerebral edema following ICH by targeting AQP4 and AVPR1,offering new therapeutic insights for ICH management.
基金supported by Zhao Guoping Academician Workstation(Hangzhou Academician Workstation)of Zhejiang Chinese Medical University,Chinese Academy of Sciences-the Alliance of National and International Science Organizations for the Belt and Road Regions Fellowship(CAS-ANSO-FP-2024-06)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB1060000)the Science and Technology Commission of Shanghai Municipality(No.YDZX20233100004032001,China).
文摘Cerebral edema is characterized by fluid accumulation,and the glymphatic system(GS)plays a pivotal role in regulating fluid transport.Using the Tenecteplase system,magnesium salt of salvianolic acid B/ginsenoside Rg1(SalB/Rg1)was injected intravenously into mice 4.5 h after middle cerebral artery occlusion and once every 24 h for the following 72 h.GS function was assessed by Evans blue imaging,near-infrared fluorescence region II(NIR-II)imaging,and magnetic resonance imaging(MRI).SalB/Rg1 had significant effects on reducing the infarct volume and hemorrhagic transformation score,improving neurobehavioral function,and protecting tissue structure,especially inhibiting cerebral edema.Meanwhile,the influx/efflux drainage of GS was enhanced by SalB/Rg1 according to NIR-II imaging and MRI.SalB/Rg1 inhibited matrix metalloproteinase-9(MMP-9)activity,reduced cleavedβ-dystroglycan(β-DG),and stabilized aquaporin-4(AQP4)polarity,which was verified by colocalization with CD31.Our findings indicated that SalB/Rg1 treatment enhances GS function and attenuates cerebral edema,accompanying the regulation of the MMP9/β-DG/AQP4 pathway.
基金supported by the National Key Research and Development Plan of China,No.2016YFC1101500the National Natural Science Foundation of China,No.11672332,11102235,31200809,81772018+1 种基金the Key Science and Technology Support Foundation of Tianjin City of China,No.17YFZCSY00620the Natural Science Foundation of Tianjin City of China,No.15JCYBJC28600,17JCZDJC35400
文摘The anti-inflammatory and antioxidant effects of exendin-4（Ex-4） have been reported previously.However,whether（Ex-4） has anti-inflammatory and antioxidant effects on high-altitude cerebral edema（HACE） remains poorly understood.In this study,two rat models of HACE were established by placing rats in a hypoxic environment with a simulated altitude of either 6000-or 7000-m above sea level（MASL） for 72 hours.An altitude of 7000 MASL with 72-hours of hypoxia was found to be the optimized experimental paradigm for establishing HACE models.Then,in rats where a model of HACE was established by introducing them to a 7000 MASL environment with 72-hours of hypoxia treatment,2,10 and,100 μg of Ex-4 was intraperitoneally administrated.The open field test and tail suspension test were used to test animal behavior.Routine methods were used to detect change in inflammatory cells.Hematoxylin-eosin staining was performed to determine pathological changes to brain tissue.Wet/dry weight ratios were used to measure brain water content.Evans blue leakage was used to determine blood-brain barrier integrity.Enzyme-linked immunosorbent assay（ELISA） was performed to measure markers of inflammation and oxidative stress including superoxide dismutase,glutathione,and malonaldehyde values,as well as interleukin-6,tumor necrosis factor-alpha,cyclic adenosine monophosphate levels in the brain tissue.Western blot analysis was performed to determine the levels of occludin,ZO-1,SOCS-3,vascular endothelial growth factor,EPAC1,nuclear factor-kappa B,and aquaporin-4.Our results demonstrate that Ex-4 preconditioning decreased brain water content,inhibited inflammation and oxidative stress,alleviated brain tissue injury,maintain blood-brain barrier integrity,and effectively improved motor function in rat models of HACE.These findings suggest that Ex-4 exhibits therapeutic potential in the treatment of HACE.
基金"973"National Key Basic Research and Development Program(No.2012CB518202)Project of Qinghai Development of Science and Technology(No.2011-N-150)
文摘Previous investigations suggest that ataxia is common and often one of the most reliable warning signs of high altitude cerebral edema(HACE). The aim of this study was to investigate the diagnostic role of ataxia in acute mountain sickness(AMS)and HACE among mountain rescuers on the quake areas,and in approaching the relation between AMS and HACE. After the earthquake on April 14,2010,approximately 24 080 lowland rescuers were rapidly transported from sea level or lowlands to the mountainous rescue sites at 3 750 ~ 4 568 m,and extremely hardly worked for an emergency treatment after arrival. Assessments of acute altitude illness on the quake areas were using the Lake Louise Scoring System. 73 % of the rescuers were found to be developed AMS. The incidence of high altitude pulmonary edema(HAPE)and HACE was 0.73 % and 0.26 %,respectively,on the second to third day at altitude. Ataxia sign was measured by simple tests of coordination including a modified Romberg test. The clinical features of 62 patients with HACE were analyzed. It was found that the most frequent,serious neurological symptoms and signs were altered mental status(50/62,80.6 %)and truncal ataxia(47/62,75.8 %). Mental status change was rated slightly higher than ataxia,but ataxia occurred earlier than mental status change and other symptoms. The earliest sign of ataxia was a vague unsteadiness of gait,which may be present alone in association with or without AMS. Advanced ataxia was correlated with the AMS scores,but mild ataxia did not correlate with AMS scores at altitudes of 3 750~4 568 m. Of them,14 patients were further examined by computerized tomographic scanning of the brain and cerebral magnetic resonance imagines were examined in another 15 cases. These imaging studies indicated that the presence of the cerebral edema was in 97 % of cases who were clinically diagnosed as HACE(28/29). Ataxia seems to be a reliable sign of advanced AMS or HACE,so does altered mental status.
文摘Vitamin K antagonists, such as warfarin and phen-procoumon, are the first-line oral anticoagulants for primary and secondary prevention of cerebral embo-lism in patients with atrial fibrillation. Although vitamin K antagonists can significantly decrease the risk of stroke, their use is limited by several important drawbacks, such as a narrow therapeutic window, the risk of intracranial and gastrointestinal bleeding, interactions with a number of drugs and nutrients, and the need for regular laboratory tests for therapy adjustment. Currently, new oral anticoagulants, such as direct thrombin inhibitors (e.g., dabigatran) and direct factor Xa inhibitors (e.g., apixaban, rivaroxaban), are being developed and tested in clinical trials. Dabigatran and rivaroxaban were recently approved for prevention of cerebral embolism in patients with atrial fibrillation. The ad-vantages of dabigatran in comparison to warfarin are a lower rate of major bleedings with dabigatran 110mg bid, a better efficacy with dabigatran 150mg bid, no clinically relevant interactions with other drugs and no need for routine coagulation monitoring. The disadvantages are the absence of antidote and the absence of routine laboratory tests for precise mea-surements of anticoagulant effect of direct thrombin/ factor Xa inhibitors. This review will focus on throm-bin and factor Xa inhibitors, which are new and promising oral anticoagulants for the prevention of cerebral embolism. We will discuss their pharmacol-ogical and clinical properties and provide the most recent updates on their clinical trials.
基金supported by grants from the National Natural Science Foundation of China(No.81270239)the Natural Science Foundation of Hubei Province of China(No.2014CFB200)
文摘The aim of this study was to investigate the possible beneficial role of telmisartan in cerebral edema after traumatic brain injury（TBI） and the potential mechanisms related to the nucleotide-binding oligomerization domain（NOD）-like receptor（NLR） pyrin domain-containing 3（NLRP3） inflammasome activation. TBI model was established by cold-induced brain injury. Male C57BL/6 mice were randomly assigned into 3, 6, 12, 24, 48 and 72 h survival groups to investigate cerebral edema development with time and received 0, 5, 10, 20 and 40 mg/kg telmisartan by oral gavage, 1 h prior to TBI to determine the efficient anti-edemic dose. The therapeutic window was identified by post-treating 30 min, 1 h, 2 h and 4 h after TBI. Blood-brain barrier（BBB） integrity, the neurological function and histological injury were assessed, at the same time, the m RNA and protein expression levels of NLRP3 inflammasome, IL-1β and IL-18 concentrations in peri-contused brain tissue were measured 24 h post TBI. The results showed that the traumatic cerebral edema occurred from 6 h, reached the peak at 24 h and recovered to the baseline 72 h after TBI. A single oral dose of 5, 10 and 20 mg/kg telmisartan could reduce cerebral edema. Post-treatment up to 2 h effectively limited the edema development. Furthermore, prophylactic administration of telmisartan markedly inhibited BBB impairment, NLRP3, apoptotic speck-containing protein（ASC） and Caspase-1 activation, as well as IL-1β and IL-18 maturation, subsequently improved the neurological outcomes. In conclusion, telmisartan can reduce traumatic cerebral edema by inhibiting the NLRP3 inflammasome-regulated IL-1β and IL-18 accumulation.
基金the National Natural Science Foundation of China, No. 30972855/C160203
文摘The present study investigated the effects of the mitochondrial calcium uniporter inhibitor ruthenium red and the agonist spermine on cerebral edema in rats with cerebral ischemia reperfusion injury. Left middle cerebral artery occlusion （MCAO） was induced in rats using the suture method. Following 24 hours of ischemic reperfusion, neurological function scores of rats with MCAO, and rats pretreated with ruthenium red and spermine were significantly lower, however, water content of brain tissue, aquaporin 4 expression and immunoglobulin G （IgG） exudation were significantly higher than those of sham-operated rats. Compared with MCAO rats and spermine-treated rats, neurological function scores were considerably higher, and brain tissue water content, aquaporin 4 expression and IgG exudation decreased in ruthenium red-treated rats. These findings suggest that preventive application of the mitochondrial calcium uniporter inhibitor ruthenium red can significantly decrease aquaporin 4 and IgG expression, influence the permeability of the blood brain barrier, and thereby decrease the extent of cerebral edema.
基金the National Natural Science Foundation of China,No.30470608,30500171
文摘BACKGROUND:Aquaporin-4(AQP-4),which is able to rapidly transport water within the brain,is highly expressed in brain tissue.It also plays an important role in the formation of cerebral edema following brain injury.However,the role of AQP-4 in the formation of cerebral edema following severe bums remains unknown.OBJECTIVE:To study changes in AQP-4 protein and mRNA expression during formation of cerebral edema following severe burns,and to explore the correlation between AQP-4 protein and mRNA expression with plasma levels of arginine vasopressin(AVP).DESIGN,TIME AND SETTING:A randomized,controlled,animal experiment was performed at the Research Center of Neuroscience,Chongqing Medical University from 2007 to 2008.MATERIALS:Biotin-labeled goat anti-rabbit antibody was provided by Beijing Zhongshan Biotechnology,China;in situ hybridization kit was provided by Wuhan Boster Biotechnology,China;rabbit anti-AQP-4 polyclonal antibody and horseradish peroxidase-labeled goat anti-rabbit IgG were provided by Chemicon,USA;AVP radioimmunoassay kit was provided by the Research Department of Neurobiology,the Second Military Medical University of Shanghai,China.METHODS:A total of 180 adult,healthy,Wistar rats were randomly assigned to control and burn groups with 30 rats in each group.The burn group was observed at five different time points:2,6,12,24,and 48 hours after burn.Hair on the mouse back was removed to expose skin on the back.After 1 day,skin with the hair removed was dipped into 100℃water for 15 seconds to induce grade III bum injury that measures 30%of total bum surface area.MAIN OUTCOME MEASURES:Brain water content was measured using the dry-wet weight method.AQP-4 protein and mRNA expressions were detected using immunohistochemistry,in situ hybridization,Western blot,and reverse transcription-polymerase chain reaction;dynamic changes in plasma AVP were detected using radioimmunoassay.RESULTS:Brain water content gradually increased following severe burn injury.AQP-4 protein and mRNA expressions were upregulated in the supraoptic nucleus,suprachiasmatic nucleus,paraventricular nucleus,hippocampus,choroid plexus,and cerebral cortex.Plasma AVP levels increased following burn injury.AQP-4 protein and mRNA expressions positively correlated with brain water content and AVP levels during formation of cerebral edema(r=0.870,0.848,P〈0.01).CONCLUSION:AQP-4 participated in the formation of cerebral edema following burn injury.Plasma AVP upregulated AQP-4 expression in brain tissue,thereby promoting formation of cerebral edema.
文摘Objective:To observe the effect of glycerol fructose combined with mannitol in the treatment of patients with clinical intracerebral hemorrhage complicated by cerebral edema and increased intracranial pressure,and to evaluate the clinical application value of this treatment.Methods:Seventy patients with cerebral hemorrhage complicated by brain edema were randomly divided into observation and control groups.Both groups had exactly the same number of study participants.There were some differences in specific treatment methods.The specific process is as follows:The control group was treated with mannitol,while the observation group was treated with dual-purpose glycerol fructose.Several important indicators after treatment in the two groups were scored,the effects between different groups were compared,and the effect of clinical treatment was evaluated.Results:The final effect was compared and analyzed.After data analysis,we found that the intracranial pressure of the observation group was lower,the volume of brain edema was significantly reduced(P<0.05),and the NIH Stroke Scale/Score(NIHSS)was lower(P<0.05).Conclusion:Using mannitol combined with glycerol fructose can achieve better treatment effect by significantly improving the problem of brain edema.
文摘Objectives Over-hydration in diabetic ketoacidosis(DKA) may increase the risk of cerebral edema in children.Methods We have organized a prospective descriptive cohort study of 38pediatric patients aged 1month to 14years,who were diagnosed with DKA with 41episodes of diabetic ketoacidosis,presented to the pediatric emergency department at the First Affiliated Hospital of Xinjiang Medical University from January 2010to February 2012.This study was approved by the Ethics Committee of The First Affiliated Hospital of Xinjiang Medical University.Results The magnitude presentation of the percentile 25%-70% was in the ratio of 5.6%(3.4%-8.2%)(6.1±4).So there was no clinical and biochemical assessment variation needed.These both of the variations,all of the diabetic ketoacidosis patient approached.Further all the patient variations were not correlated with the amplitude of variation and magnitude presentation and did not affect the fluid concentration and the quantity of the fluid was 47.8mL / kg(36.556.3) in the first 12hours.Conclusion For the conclusion of the exact parameters and the magnitude variations of the fluid in the patients of diabetic ketoacidosis,all of the conformations need study on the larger scale.
文摘High grade gliomas are the commonest intrinsic brain tumours and account for more average years of life lost than all the common cancers. It has become the commonest cause of cancer death in men under the age of 45 and women under the age of 35. Although surgical resection can greatly reduce tumour bulk, complete excision is virtually impossible due to the infiltrative nature of these tumours. In an attempt to treat the infiltrating tumour cells, there has been much interest in using local therapies inserted at the time of surgery. The authors report a case of fatal cerebral edema unresponsive to aggressive medical and surgical assessment that finally evolved to premature death in the early postsurgical period, after the craniotomy and implantation of Gliadel wafers. They note that high doses of dexamethasone were insufficient to prevent cerebral edema and death. A search for corticosteroid use and dosing for patients treated with Gliadel wafers in the published literature revealed no recommendations on the doses of steroids to be administered. In our opinion this is a very important issue and maybe the key point for the treatment of this disease, and may need to be addressed with treatment guidelines in the near future in order to ensure better results on patient’s survival. Prior to this case review there had been two similar report but a later presentation. So we think that this is the first case report of acute fulminant cerebral edema secondary to gliadel wafers in the early period.
基金the Social Development Foundation Program of Liaoning Province,No.99225003
文摘BACKGROUND: It has shown that magnetic field can improve blood circulation, decrease blood viscosity, inhibit free radicals, affect Ca2+ flow in nerve cells, control inflammatory and immunological reaction, and accelerate nerve cell regeneration. In addition, protective effect of magnetic field, which acts as an iatrophysics, on ischemic brain tissues has been understood gradually. OBJECTIVE: To investigate the effects of rotating magnetic field (RMF) on volume of cerebral infarction, cerebral edema and metabolism of free radicals in rats after cerebral ischemia/reperfusion injury. DESIGN: Randomized controlled animal study. SETTING: Rehabilitation Center of disabled children, Liaoniang; Department of Rehabilitation, the Second Affiliated Hospital, China Medical University; Department of Rehabilitation Physiotherapy, the First Affiliated Hospital, China Medical University. MATERIALS: A total of 70 healthy Wistar rats aged 18-20 weeks of both genders were selected and randomly divided into 3 groups: sham operation group with 12 rats, control group with 20 rats and treatment group with 38 rats. The treatment group included 4 time points: immediate reperfusion with 6 ones, 6-hour reperfusion with 20 ones, 12-hour reperfusion with 6 ones and 18-hour reperfusion with 6 rats. Main instruments were detailed as follows: magnetic head of rotating magnetic device was 6 cm in diameter; magnetic induction intensity at the surface of magnetic head was 0.25 T in silence; the maximal magnetic induction intensity was 0.09 T at the phase of rotation; the average rotating speed was 2500 r per minute. METHODS: The experiment was carried out in the China Medical University in March 2003. Focal cerebral ischemic animal models were established with modified Longa’s method. Operation was the same in the sham operation, but the thread was inserted as 10 mm. Neurologic impairment was assessed with 5-rating method to screen out cases. Those survivals with grade 1 and grade 2 after ischemia for 2 hours and reperfusion for 24 hours were included in the control group and treatment group. Those in the sham operation group and control group were not treated with RMF. Magnetic head was directed towards the head of rats of the treatment group, and the magnetic head was about 7 mm from skin, treated for 15 minutes. The rats were decapitated to take out brains at 24 hours after reperfusion in each group. Water content of brain and volume of cerebral infarction were assessed with wet-dry weight method and TTC staining, respectively. Activity of superoxide dismutase (SOD), content of malondialdehyde (MDA) and change of brain histomorphology in brain tissue of ischemic side were analyzed. MAIN OUTCOME MEASURES: ① Volume of cerebral infarction and changes of water content in brain; ② measurements of SOD and MDA contents in brain tissue of rats in all groups. RESULTS: A total of 70 qualified animals were involved in the final analysis after rejecting the death and unqualified animal models. ① Water content of brain: Water content of brain in the treatment was less than that in the control group at any time point except the immediate time point, and cerebral edema was relieved [(2.48±0.22)%, (2.32±0.19)%, (2.23±0.36)%, (2.91±0.44)%, P < 0.05]. In addition, there were no significant differences among 6-hour, 12-hour and 18-hour reperfusion groups (P > 0.05). ② Volume of cerebral infarction: The absolute volume of cerebral infarction in the treatment group was smaller than that in the control group [(128.21±15.05), (171.22±40.50) mm3, t =2.438, P < 0.05], and the relative volume of cerebral infarction was smaller than that in the control group [(20.22±1.44)%, (25.17±3.85)%, t =2.95, P < 0.05]. ③ Contents of SOD and MDA in brain tissues: Compared with the control group, the SOD content in the brain tissue in the treatment group increased [(54.54±3.85), (69.52±5.88) kNU/g, t =5.568, P < 0.05], while the MDA content decreased [(0.85±0.06), (1.03±0.09) μmol/g, t =4.076, P < 0.05]. ④ General morphological observation: General morphology manifested that the edema was distinct in the right cerebral hemisphere in the control group, showing fat-like white, shallow anfractuosity, flat gyria, brittle tissue and easy to break up. The edema of right cerebral hemisphere was light and surface was hyperaemia in the treatment group. CONCLUSION: RMF may improve anti-oxidative ability of brain tissue of rats with acute focal cerebral ischemia/reperfusion injury and reduce volume of cerebral infarction and degrees of cerebral edema.
文摘Objective:To study the relationship of cerebral edema with apoptosis, inflammatory factor generation and AQPs expression in the rat model with closed craniocerebral injury.Methods:Male SD rats were selected as experimental animals and divided into model group and control group. Model group were established into the closed craniocerebral injury models and control group received sham operation. The water content of damaged brain tissue as well as the expression of apoptosis molecules, the generation of inflammatory factors and the expression of aquaporins (AQPs) molecules were measured 7 d after model establishment.Results:The water content of brain tissue of model group was significantly higher than that of control group;Homer1a, Pim-3, Bcl-2, AQP1, AQP4 and AQP9 mRNA expression in brain tissue of model group were significantly lower than those of control group while Cdk5, FasL and Caspase-3 mRNA expression as well as NF-kB, TNF-α, IL-1β, IL-6 and p-JNK generation were significantly higher than those of control group. Homer1a, Pim-3, Bcl-2, AQP1, AQP4 and AQP9 mRNA expression in brain tissue of model group were negatively correlated with water content while Cdk5, FasL and Caspase-3 mRNA expression as well as NF-kB, TNF-α, IL-1β, IL-6 and p-JNK generation were positively correlated with water content.Conclusion:The excessive apoptosis, increased inflammatory factor generation and decreased AQPs expression are closely related to the occurrence of cerebral edema in the process of closed craniocerebral injury.
文摘Objective To investigate the expression of cytochrome C in perihematomal brain tissue and its relationship with the histopathological change and formation of cerebral edema in patients with hypertensive cerebral hemorrhage.Methods Thirty four patients(23 male,11 female) of hypertensive cerebral hemorrhage in hospital from Sep.2001 to Sep.2002 were selected with a mean age 55.6± 10.2 years(from 35 to 75 years).The mean volume of hemorrhagic blood was 50.4±11.6 ml(from 25 to 85 ml).The perihematomal brain tissue was obtained from the minimally invasive surgery.Histopathological change and expressions of cytochrome C in perihematomal brain tissue was detected by histopathological and immunohistochemical techniques.The volume of perihematomal cerebral edema was determined by computed tomographic scan before operation.The results of staining and the volume of perihematomal cerebral edema were analyzed with double blind fashion.Results Perihematomal cerebral edema were found 12-72h after cerebral hemorrhage.Myelin sheath degeneration,condensation of nucleus and typical apopototic body were observed in perihematomal brain tissue.Expression of cytochrome C in perihematomal brain tissue was observed at 4 h and reached peak around 48-72 h after cerebral hemorrhage.Cytochrome C expressed higher positively in 16 patients and lower positively in 13 patients.Cytochrome C expression was not detected only in 5 patints.There were significant differences in volume of perihematomal cerebral edema with different expression of cytochrome C in perihematomal brain tissue(P<0.01).Conclusions Cytochrome C expression was upregulated in perihematomal brain tissue in patients with hypertensive cerebral hemorrhage.Cytochrome C might involve in the histopathological change and the formation of perihematomal cerebral
基金the National Natural Science Foundation of China, No. 81041019the National High-Technology Research and Development Program of China (863 Program), No.2006AA02Z436
文摘This study sought to elucidate the genetic correlation of cerebral venous sinus thrombosis caused by a hereditary antithrombin deficiency in a Chinese family, at the genetic and protein levels. A nonsense mutation from C to T on locus 6431 in exon 3B of the antithrombin gene was observed, leading to an arginine （CGA） to stop codon （TGA） change in the protein. This is the first report of this mutation in China. Ineffective heparin therapy in the propositus patient is associated with a lack of heparin binding sites after antithrombin gene mutation. Characteristic low intracranial pressure in the acute phase might be specific to this patient with cerebral venous sinus thrombosis.
基金supported by the National Key Research and Devel-opment Program of China(2024YFB4707700,2021YFF1200800)the National Natural Science Foundation of China(82170256,82171861)+4 种基金Guangdong Major Project of Basic and Applied Basic Research(2023B0303000005)Guangdong Provincial Special Support Program for Prominent Talents(2021JC06Y656)Science and Technology Plan-ning Project of Guangdong Province(2022B1212010010)the Special Project of Dengfeng Program of Guangdong Provincial People’s Hospital(KJ012019119)Guangzhou Association for Science&Technology,grant number[2024D010].
文摘Vasogenic edema,caused by the disruption of the blood-brain barrier(BBB),is a significant pathological factor in high-altitude cerebral edema(HACE).Due to the rapid progression and high mortality rate of HACE,prophy-lactic treatment is important.Mesenchymal stem cell exosomes(MSC-EXO)are increasingly being used in tissue injury repair,and research suggests that appropriate conditioning can enhance the targeted efficacy of exosome therapy.Our in vitro experiments revealed that hypoxia preconditioned MSC-EXO(H-EXO)significantly out-performed normoxic MSC-EXO(N-EXO)in multiple protective aspects.Specifically,H-EXO demonstrated enhanced capacity to mitigate hypoxia-induced aberrant angiogenesis,maintain vascular endothelial cell viability,and suppress ROS accumulation and apoptotic signaling under hypoxic stress.Mechanistic investiga-tion identified miR-125a-5p cargo in H-EXO as a key mediator of RTEF-1 targeted inhibition during hypoxic exposure.In corresponding in vivo studies,H-EXO administration effectively attenuated HACE-induced patho-logical angiogenesis while maintaining crucial vascular homeostasis markers.The therapeutic effects manifested through three principal aspects:1)downregulation of RTEF-1/VEGF hyperexpression,2)modulation of VEcadherin,SMA,and PDGFRα+βexpression to preserve BBB integrity,and 3)concurrent protection of neuro-vascular functions against HACE-induced damage.This investigation elucidates the miR-125a-5p/RTEF-1 axis as the central mechanism through which hypoxic preconditioning enhances MSC-EXO’s endothelial protective properties.Our findings establish H-EXO’s multimodal therapeutic potential,demonstrating its capacity to simultaneously inhibit pathological angiogenesis,restore BBB function,and protect neural tissue under hypoxic stress conditions.The study elucidates key mechanisms underlying clinical prevention and management of HACE by delineating H-EXO’s preventive mechanisms against hypoxia-induced cerebrovascular injury.
基金The study was supported by grants from the National Natural Science Foundation of China(31671206 and 81873924)Key Laboratory of Extreme Environmental Medicine,the Ministry of Education(KL2019GY011).
文摘High-altitude cerebral edema(HACE)is a potentially fatal encephalopathy associated with a time-dependent exposure to the hypobaric hypoxia of altitude.The formation of HACE is affected by both vasogenic and cytotoxic edema.The over-activated microglia potentiate the damage of blood-brain barrier(BBB)and exacerbate cytotoxic edema.In light with the activation of microglia in HACE,we aimed to investigate whether the over-activated microglia were the key turning point of acute mountain sickness to HACE.In in vivo experiments,by exposing mice to hypobaric hypoxia(7000 m above sea level)to induce HACE model,we found that microglia were activated and migrated to blood vessels.Microglia depletion by PLX5622 obviously relieved brain edema.In in vitro experiments,we found that hypoxia induced cultured microglial activation,leading to the destruction of endothelial tight junction and astrocyte swelling.Up-regulated nuclear respiratory factor 1(NRF1)accelerated pro-inflammatory factors through transcriptional regulation on nuclearfactorkappa B p65(NF-kB p65)and mitochondrial transcription factorA(TFAM)in activated microglia under hypoxia.NRF1 also up-regulated phagocytosis by transcriptional regulation on caveolin-1(CAV-1)and adaptorrelated protein complex 2 subunit beta(AP2B1).The present study reveals a new mechanism in HACE:hypoxia over-activates microglia through up-regulation of NRF1,which both induces inflammatory response through transcriptionally activating NF-kB p65 and TFAM,and enhances phagocytic function through up-regulation of CAV-1 and AP2B1;hypoxia-activatedmicroglia destroy the integrity of BBB and release pro-inflammatory factors that eventually induce HACE.
基金Tibet Science and Technology Program(No.XZ202201ZY0002G)Sichuan Science and Technology Program(No.2021YFQ0030).
文摘Background Acute high-altitude illness(AHAI)refers to a series of syndromes including acute mountain sickness(AMS),high-altitude pulmonary edema(HAPE)and high-altitude cerebral edema(HACE).Among these,HACE is a severe and potentially life-threatening condition that can occur when individuals ascend to high altitudes.It is often characterized by ataxia,confusion,and altered mental status.Without appropriate treatment,HACE can rapidly progress to coma,but seizures are infrequent in occurrence.Case presentation Here,we report a severe HACE patient with coma and status epilepticus.The patient is a 23-year-old male who was visiting Lhasa for the first time.He initially experienced headaches and dizziness on the first day,and then he was found in coma with limb convulsions on the next day.Immediate medical attention was sought,and brain CT and MRI scans showed reversible white matter lesions,especially in the corpus callosum and subcortical white matter.Although the lesions disappeared on T1 and T2 sequences,microbleeds were observed on the SWI sequence.After treatment with tracheal intubation,glucocorticoids and hyperbaric oxygen,the cerebral edema has resolved and the clinical symptoms improved,the patient has no seizures anymore.Conclusions HACE typically follows AMS and poses a significant risk to life.Clinical manifestations mainly include ataxia,alterations of behavior,and impaired consciousness,with severe cases progressing to coma.Seizures,though rarely observed,may occur.Imaging shows reversible white matter lesions,with microbleeds being a significant and persistent imaging marker over time.Administration of glucocorticoids plays a crucial role in treatment.Despite experiencing seizures,this patient did not experienced any further episodes once his condition improved.
