OBJECTIVE:To observe the effects of bloodletting puncture at Jing-Well points in the distal ends of the finger and toe on survival rate,survival time,and brain edema in rats with cerebral ischemia.METHODS:Fifty-four m...OBJECTIVE:To observe the effects of bloodletting puncture at Jing-Well points in the distal ends of the finger and toe on survival rate,survival time,and brain edema in rats with cerebral ischemia.METHODS:Fifty-four male Sprague-Dawley rats were randomly divided into five groups:normal,sham operation,model,bloodletting puncture at Jing-Well points in distal ends of finger and toe,and puncture without bloodletting at these points.Middle cerebral artery occlusion models were established according to Longa's method.The brains were taken 48 h after the model was established.Brain water content,brain density,brain coefficient,survival rate,and survival time in each group were measured.RESULTS:After bloodletting puncture,the survival time of the rats was prolonged,their brain water content and brain coefficient were reduced,and brain density was increased.CONCLUSION:Bloodletting puncture at Jing-Well points in the distal ends of the finger and toe can improve function in ischemic brain edema.展开更多
Intracranial hypertension is a major cause of morbidity and mortality of patients suffering from fulminant hepatic failure. The etiology of this intracranial hypertension is not fully determined, and is probably multi...Intracranial hypertension is a major cause of morbidity and mortality of patients suffering from fulminant hepatic failure. The etiology of this intracranial hypertension is not fully determined, and is probably multifactorial, combining a cytotoxic brain edema due to the astrocytic accumulation of glutamine, and an increase in cerebral blood volume and cerebral blood flow, in part due to inflammation, to glutamine and to toxic products of the diseased liver. Validated methods to control intracranial hypertension in fulminant hepatic failure patients mainly include mannitol, hypertonic saline, indomethacin, thiopental, and hyperventilation. However all these measures are often not sufficient in absence of liver transplantation, the only curative treatment of intracranial hypertension in fulminant hepatic failure to date. Induced moderate hypothermia seems very promising in this setting, but has to be validated by a controlled, randomized study. Artificial liver support systems have been under investigation for many decades. The bioartiflcial liver, based on both detoxification and swine liver cells, has shown some efficacy on reduction of intracranial pressure but did not show survival benefit in a controlled, randomized study. The Molecular Adsorbents Recirculating System has shown some efficacy in decreasing intracranial pressure in an animal model of liver failure, but has still to be evaluated in a phase Ⅲ trial.展开更多
OBJECTIVE： To investigate the relationship of aquaporin 4 （AQP4） and brain edema. DATA SOURCES： Using the terms of ＂aquaporin-4, brain edema＂, we searched PubMed database to identify studies published from Janua...OBJECTIVE： To investigate the relationship of aquaporin 4 （AQP4） and brain edema. DATA SOURCES： Using the terms of ＂aquaporin-4, brain edema＂, we searched PubMed database to identify studies published from January 1997 to April 2006 in the English languages. Meanwhile, we also searched China National Knowledge Infrastructure （CNKI） for related studies. STUDY SELECTION： The collected data were selected firstly. Studies on AQP4 and brain edema were chosen and their full-texts were searched for, and those with repetitive or review studies were excluded. DATA EXTRACTION： Totally 146 related studies were collected, 42 of them were involved and the other 104 studies were used for reading reference data. DATA SYNTHESIS： AQP4 is a selective water permeable integral membrane protein. It is mainly expressed in astrocytes and ependymocyte, and is the important structural basis for water regulation and transportation between glial cells and cerebrospinal fluid or vessels. Phosphorylation is involved in the regulation of AQP4. AQP4 participates in the formation of brain edema caused by various factors. Studies on the structure and pathological changes of AQP4 are still in the initial stage, and the role and mechanism of AQP4 in the formation of brain edema is very unclear. CONCLUSION： AQP4 plays a critical regulating role in the formation of ischemic brain edema, but whether it is regulated by drugs lacks reliable evidence.展开更多
AIM:To study the blood-brain barrier integrity,brain edema, animal behavior and ammonia plasma levels in prehepatic portal hypertensive rats with and without acute liver intoxication. METHODS:Adults male Wistar rats w...AIM:To study the blood-brain barrier integrity,brain edema, animal behavior and ammonia plasma levels in prehepatic portal hypertensive rats with and without acute liver intoxication. METHODS:Adults male Wistar rats were divided into four groups.Group Ⅰ:sham operation;Ⅱ:Prehepatic portal hypertension,produced by partial portal vein ligation;Ⅲ: Acetaminophen intoxication and Ⅳ:Prehepatic portal hypertension plus acetaminophen.Acetaminophen was administered to produce acute hepatic injury.Portal pressure,liver serum enzymes and ammonia plasma levels were determined.Brain cortex water content was registered and trypan blue was utilized to study blood brain barrier integrity.Reflexes and behavioral tests were recorded. RESULTS:Portal hypertension was significantly elevated in groups Ⅱ and Ⅳ.Uver enzymes and ammonia plasma levels were increased in groups Ⅱ,Ⅲ and Ⅳ.Prehepatic portal hypertension (group Ⅱ),acetaminophen intoxication (group Ⅲ) and both (group Ⅳ) had changes in the blood brain-barrier integrity (trypan blue) and hyperammonemia.Cortical edema was present in rats with acute hepatic injury in groups Ⅲ and Ⅳ.Behavioral test (rota rod) was altered in group Ⅳ. CONCLUSION:These results suggest the possibility of another pathway for cortical edema production because blood brain barrier was altered (vasogenic) and hyperammonemia was registered (oltotoxic).Group Ⅳ,with behavioral altered test,can be considered as a model for study at an early stage of portal-systemic encephalopathy.展开更多
To investigate the role of AQP9 in brain edema, the expression of AQP9 in an infectious rat brain edema model induced by the injection of lipopolysaccharide （LPS） was examined. Immuno- histochemistry and reverse tra...To investigate the role of AQP9 in brain edema, the expression of AQP9 in an infectious rat brain edema model induced by the injection of lipopolysaccharide （LPS） was examined. Immuno- histochemistry and reverse transcription-polymerase chain reaction （RT-PCR） analysis demonstrated that the expressions of AQP9 mRNA and protein at all observed intervals were significantly increased in LPS-treated animals in comparison with the control animals. Time-course analysis showed that the first signs of blood-brain barrier disruption and the increase of brain water content in LPS-treated animals were evident 6 h after LPS injection, with maximum value appearing at 12 h, which coincided with the expression profiles of AQP9 mRNA and protein in LPS-treated animals. The further correlation analysis revealed strong positive correlations among the brain water content, the disruption of the blood-brain barrier and the enhanced expressions of AQP9 mRNA and protein in LPS-treated animals. These results suggested that the regulation of AQP9 expression may play im- portant roles in water movement and in brain metabolic homeostasis associated with the pathophysi- ology of brain edema induced by LPS injection.展开更多
The experimental model of traumatic brain injury was established in Sprague-Dawley rats according to Feeney＇s free falling method. The brains were harvested at 2, 6 and 24 hours, and at 3 and 5 days after injury. Cha...The experimental model of traumatic brain injury was established in Sprague-Dawley rats according to Feeney＇s free falling method. The brains were harvested at 2, 6 and 24 hours, and at 3 and 5 days after injury. Changes in brain water content were determined using the wet and dry weights. Our results showed that water content of tissue significantly increased after traumatic brain injury, and reached minimum at 24 hours. Hematoxylin-eosin staining revealed pathological impairment of brain tissue at each time point after injury, particularly at 3 days, with nerve cell edema, degenera- tion, and necrosis observed, and the apoptotic rate significantly increased. Immunohistochemistry and western blot analysis revealed that the expression of occludin at the injured site gradually de- creased as injury time advanced and reached a minimum at 3 days after injury; the expression of connexin 43 gradually increased as injury time advanced and reached a peak at 24 hours after in-jury. The experimental findings indicate that changes in occludin and connexin 43 expression were consistent with the development of brain edema, and may reflect the pathogenesis of brain injury.展开更多
AIM:To compare rifaximin and insulin-like growth factor(IGF)-1 treatment of hyperammonemia and brain edema in cirrhotic rats with portal occlusion.METHODS:Rats with CCl4-induced cirrhosis with ascites plus portal vein...AIM:To compare rifaximin and insulin-like growth factor(IGF)-1 treatment of hyperammonemia and brain edema in cirrhotic rats with portal occlusion.METHODS:Rats with CCl4-induced cirrhosis with ascites plus portal vein occlusion and controls were randomized into six groups:Cirrhosis;Cirrhosis + IGF-1;Cirrhosis + rifaximin;Controls;Controls + IGF-1;and Controls + rifaximin.An oral glutamine-challenge test was performed,and plasma and cerebral ammonia,glucose,bilirubin,transaminases,endotoxemia,brain water content and ileocecal cultures were measured and liver histology was assessed.RESULTS:Rifaximin treatment significantly reduced bacterial overgrowth and endotoxemia compared with cirrhosis groups,and improved some liver function parameters(bilirubin,alanine aminotransferase and aspartate aminotransferase).These effects were associated with a significant reduction in cerebral water content.Blood and cerebral ammonia levels,and area-underthe-curve values for oral glutamine-challenge tests were similar in rifaximin-treated cirrhotic rats and control group animals.By contrast,IGF-1 administration failed to improve most alterations observed in cirrhosis.CONCLUSION:By reducing gut bacterial overgrowth,only rifaximin was capable of normalizing plasma and brain ammonia and thereby abolishing low-grade brain edema,alterations associated with hepatic encephalopathy.展开更多
Intracranial hypertension is a serious threat to the health of neurosurgical patients.At present,there is a lack of a safe and e®ective technology to monitor intracranial pressure(ICP)accurately and nondestructiv...Intracranial hypertension is a serious threat to the health of neurosurgical patients.At present,there is a lack of a safe and e®ective technology to monitor intracranial pressure(ICP)accurately and nondestructively.In this paper,based on near infrared technology,the continuous nonde-structive monitoring of ICP change caused by brain edema was studied.The rat brain edema models were constructed by lipopolysaccharide.The ICP monitor and the self-made near infrared tissue parameter measuring instrument were used to monitor the invasive intracranial pressure and the reduced scattering coe±cient of brain tissue during the brain edema development.The results showed that there was a negative correlation between the reduced scattering coe±cient(690nm and 834nm)and ICP,and then the mathematical model was established.The experimental results promoted the development of nondestructive ICP monitoring based on near infrared technology.展开更多
BACKGROUND： Stereo-tactic radiation therapy （SRT） is widely used to treat intracranial diseases, but some patients suffered from radiation induced brain edema after SRT. Once radiation induced brain edema occurs, t...BACKGROUND： Stereo-tactic radiation therapy （SRT） is widely used to treat intracranial diseases, but some patients suffered from radiation induced brain edema after SRT. Once radiation induced brain edema occurs, the treatment is quite difficult, and it always leads to a poor outcome. Dexamethasone has certain therapeutic effect on traumatic brain edema, but the biological mechanism is still unclear. OBJECTIVE ： To observe the effect of dexamethasone on the neutrophil expression of CD18.DESIGN ： A randomized control observation.SETTING： Changhai Hospital of the Second Military Medical University of Chinese PLA. MATERIALS ： The experiment was carried out in Changhai Hospital of the Second Military Medical University of Chinese PLA from January 1999 to December 1999. Twenty SD rats （male and female each in half） weighing （250±50） g were used. METHODS： Twenty SD rats were divided into four groups at random. ① Blank control group （n=5）： The rats were not treated without dexamethasone or irradiation;② Irradiation group （n=5）： The rats were given irradiation but no dexamethasone treatment; ③ Irradiation＋1 mg/kg dexamethasone group （n=5）; The rats were treated with irradiation and dexamethasone of 1 mg/kg; ④Irradiation＋5 mg/kg dexamethasone group （n=5）： The rats were treated with irradiation and dexamethasone of 5 mg/kg. The heads of the rats were irradiated with 10 MeV X-ray （30 Gy）, and brain tissue was removed after 2 weeks to observe the pathological changes. Blood samples were taken from the carotid artery, gradient centrifugation was used, and neutrophile layer was obtained, the level of neutrophile expression of CD18 mRNA and quantity of membrane proteins in blood were detected with Northern blot and flow cytometry respectively. MAIN OUTCOME MEASURES： ① Blood cell count; ② Pathological results; ③ level of neutrophile expression of CD18 mRNA and quantity of membrane proteins. RESULTS ： All the 20 SD rats were involved in the analysis of results without deletion. At 2 weeks after irradiation, obvious cell injury could be observed under light microscope. The level of neutrophile expression of CD18 mRNA and quantity of membrane proteins in blood were obviously increased, but the severity of cell injury was relieved in the irradiation＋1 and 5 mg/kg dexamethasone groups, and the CD18 expression was markedly suppressed （P 〈 0.05）, and the suppression was more obvious in the irradiation＋5 mg/kg dexamethasone group than in the irradiation＋1 mg/kg dexamethasone group （P 〈 0.01 ）. CONCLUSION： Dexamethasone can reduce the radiation induced brain edema by inhibiting the expression of CD18.展开更多
The present study evaluated the effect of dl-3-n-butylphthalide(NBP) ,a novel brain protective agent, on brain edema in rats following focal ischemia. Edema was induced by occluding the right middle cerebral artery (M...The present study evaluated the effect of dl-3-n-butylphthalide(NBP) ,a novel brain protective agent, on brain edema in rats following focal ischemia. Edema was induced by occluding the right middle cerebral artery (MCAO).producing permanent focal ischemia in the right cerebral hemisphere,which developed ip-silateral brain edema reproducibly. Edema was assessed 24 h after MCA occlusion by determining the brain water content from wet and dry weight measurements,and the sodium,potassium concentrations with ion-selective electrodes. In this model,NBP at the dose of 80,160 and 240 mg/kg po 15 min after MCAO prevented from brain edema in a dose-dependent manner. A significant reduction of sodium content and an increase in potassium level were observed in all drug-treated groups. It showed that NBP strongly attenuated brain water entry,sodium accumulation and potassium loss. Nimodipine treatment(5mg/kg sc) also reduced brain edema (P<0. 05). The results suggest that a strong anti-edema activity of NBP may play an important role to contribute to the treatment of ischemic damage.展开更多
The aquaporin-4(AQP4)is a highly selective membrane protein.It is important for the body to maintain the water balance between internal and external environment of cells,the studies have found that the abnormal expres...The aquaporin-4(AQP4)is a highly selective membrane protein.It is important for the body to maintain the water balance between internal and external environment of cells,the studies have found that the abnormal expression of AQP4 is related to the occurrence of many diseases.The cerebral edema is the most common and serious complication of brain trauma,and its pathogenesis is closely related to AQP4.The development of multimodal magnetic resonance imaging(M-MRI)could been provided imaging basis for accurate diagnosis of traumatic brain edema.In recent years,the correlation between AQP4 and M-MRI has become a hotspot of research.This paper reviews the research progress on the correlation between AQP4 expression in traumatic cerebral edema and M-MRI.展开更多
Acute traumatic brain edema models were established in SD rats by dropping weight methods.We observed the therapeutic effect of Cyproheptadine(Cyp)on traumatic brain edema.It was shown that Cyp could obviously reduce ...Acute traumatic brain edema models were established in SD rats by dropping weight methods.We observed the therapeutic effect of Cyproheptadine(Cyp)on traumatic brain edema.It was shown that Cyp could obviously reduce the brain water content,decrease the releae or LDH,reduce the seventy of the pathological changes at the injury areas,increase the SOD activity and decrease the production of MDA in SD rats.The results suggest that Cyp has obvious.therapeutic effect on traumatic brain edema.The mechanism may be that it can increase the activity or clearance enzyme of free radical,inhibit lipid peroxldation and reduce intracellular Ca2+-overload.展开更多
Objective: To determine whether VEGF plays a role in the development of peritumoral brain edema. Methods 50 meningioma patients and their VEGF expression were studied. We took a monoclonal antibody from mouse to VEGF ...Objective: To determine whether VEGF plays a role in the development of peritumoral brain edema. Methods 50 meningioma patients and their VEGF expression were studied. We took a monoclonal antibody from mouse to VEGF to stain the tumor cells, the vascular endothelial cells and the interstitial cells. The severity of brain edema was evaluated according to CT or MR scans by the following equation: edema index= V tumor +edema /Vtumor. The relationship between VEGF expression and edema index was analyzed statistically. Results VEGF was expressed in meningioma tumor cells, which is usually concentrated at the peripheral sites of the tumor. There was a positive linear correlation between the expression and the brain edema index. Conclusion VEGF may play a role in the development of peritumoral brain edema in meningioma patient.展开更多
Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter injury.Microglia,which are the key immune cells...Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter injury.Microglia,which are the key immune cells in the central nervous system,maintain homeostasis in the neural environment,support neurons,mediate apoptosis,participate in immune regulation,and have neuroprotective effects.Increasing evidence has shown that microglia play a pivotal role in the pathogenesis of subarachnoid hemorrhage and affect the process of injury and the prognosis of subarachnoid hemorrhage.Moreover,microglia play certain neuroprotective roles in the recovery phase of subarachnoid hemorrhage.Several approaches aimed at modulating microglia function are believed to attenuate subarachnoid hemorrhage injury.This provides new targets and ideas for the treatment of subarachnoid hemorrhage.However,an in-depth and comprehensive summary of the role of microglia after subarachnoid hemorrhage is still lacking.This review describes the activation of microglia after subarachnoid hemorrhage and their roles in the pathological processes of vasospasm,neuroinflammation,neuronal apoptosis,blood–brain barrier disruption,cerebral edema,and cerebral white matter lesions.It also discusses the neuroprotective roles of microglia during recovery from subarachnoid hemorrhage and therapeutic advances aimed at modulating microglial function after subarachnoid hemorrhage.Currently,microglia in subarachnoid hemorrhage are targeted with TLR inhibitors,nuclear factor-κB and STAT3 pathway inhibitors,glycine/tyrosine kinases,NLRP3 signaling pathway inhibitors,Gasdermin D inhibitors,vincristine receptorαreceptor agonists,ferroptosis inhibitors,genetic modification techniques,stem cell therapies,and traditional Chinese medicine.However,most of these are still being evaluated at the laboratory stage.More clinical studies and data on subarachnoid hemorrhage are required to improve the treatment of subarachnoid hemorrhage.展开更多
S.Lehrer and P.H.Rheinstein,“Alignment of Human Aquaporin 4 and fß-Amyloid Proteins May Indicate Involvement of fß-Amyloid in Brain Water Homeostasis and Prevention of Brain Edema,”Chronic Diseases and Tra...S.Lehrer and P.H.Rheinstein,“Alignment of Human Aquaporin 4 and fß-Amyloid Proteins May Indicate Involvement of fß-Amyloid in Brain Water Homeostasis and Prevention of Brain Edema,”Chronic Diseases and Translational Medicine 9(2023):177-181.https://doi.org/10.1002/cdt3.64.展开更多
Objective:To characterize the expression of aquaporin-4(AQP4),one of the aquaporins(AQPs),in human brainspecimens from patients with traumatic brain injury or brain tumors.Methods:Nineteen hnman brain specimens were o...Objective:To characterize the expression of aquaporin-4(AQP4),one of the aquaporins(AQPs),in human brainspecimens from patients with traumatic brain injury or brain tumors.Methods:Nineteen hnman brain specimens were obtahledfrom the patients with traumatic brain injury,brain tumors,benign meningioma or early stage hemorrhagic stroke.MRI or CTimaging was used to assess brain edema.Hematoxylin and eosm staining were used to evaluate cell damage,Immunohistochem-istry was used to detect the AQP4 expression.Results:AQP4 expression was increased from 15 h to at least 8 d after injury.AQP4immunoreactivity was strong around astrocytomas,ganglioglioma and metastatic adenocarcinoma.However,AQP4 immunore-activity was only found in the centers of astrocytomas and ganglioglioma,but not in metastatic adenocarcinoma derived from lung.Conclusion:AQP4 expression increases in human brains alter traumatic brain injury,within brain-derived tumors,and aroundbrain tumors.展开更多
Traumatic brain injury induces potent inflammatory responses that can exacerbate secondary blood-brain barrier（BBB） disruption, neuronal injury, and neurological dysfunction. Dexmedetomidine is a novel α2-adrenergi...Traumatic brain injury induces potent inflammatory responses that can exacerbate secondary blood-brain barrier（BBB） disruption, neuronal injury, and neurological dysfunction. Dexmedetomidine is a novel α2-adrenergic receptor agonist that exert protective effects in various central nervous system diseases. The present study was designed to investigate the neuroprotective action of dexmedetomidine in a mouse traumatic brain injury model, and to explore the possible mechanisms. Adult male C57 BL/6 J mice were subjected to controlled cortical impact. After injury, animals received 3 days of consecutive dexmedetomidine therapy（25 μg/kg per day）. The modified neurological severity score was used to assess neurological deficits. The rotarod test was used to evaluate accurate motor coordination and balance. Immunofluorescence was used to determine expression of ionized calcium binding adapter molecule-1, myeloperoxidase, and zonula occluden-1 at the injury site. An enzyme linked immunosorbent assay was used to measure the concentration of interleukin-1β（IL-1β）, tumor necrosis factor α, and IL-6. The dry-wet weight method was used to measure brain water content. The Evans blue dye extravasation assay was used to measure BBB disruption. Western blot assay was used to measure protein expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3（NLRP3）, caspase-1 p20, IL-1β, nuclear factor kappa B（NF-κB） p65, occluding, and zonula occluden-1. Flow cytometry was used to measure cellular apoptosis. Results showed that dexmedetomidine treatment attenuated early neurological dysfunction and brain edema. Further, dexmedetomidine attenuated post-traumatic inflammation, up-regulated tight junction protein expression, and reduced secondary BBB damage and apoptosis. These protective effects were accompanied by down-regulation of the NF-κB and NLRP3 inflammasome pathways. These findings suggest that dexmedetomidine exhibits neuroprotective effects against acute（3 days） post-traumatic inflammatory responses, potentially via suppression of NF-κB and NLRP3 inflammasome activation.展开更多
This study used electroacupuncture at Renzhong （DU26） and Baihui （DU20） in a rat model of cerebral ischemia/reperfusion injury. Neurological deficit scores, western blotting, and reverse transcription-PCR results ...This study used electroacupuncture at Renzhong （DU26） and Baihui （DU20） in a rat model of cerebral ischemia/reperfusion injury. Neurological deficit scores, western blotting, and reverse transcription-PCR results demonstrated that electroacupuncture markedly reduced neurological deficits, decreased corpus striatum aquaporin-4 protein and mRNA expression, and relieved damage to the blood-brain barrier in a rat model of cerebral ischemia/reperfusion injury. These results suggest that electroacupuncture most likely protects the blood-brain barrier by regulating aquaporin-4 expression following cerebral ischemia/reperfusion injury.展开更多
DI-3n-butyiphthalide can effectively treat cerebral ischemia; however, the mechanisms underlying the effects of dl-3n-butylphthalide on microcirculation disorders following diffuse brain injury remain unclear. In this...DI-3n-butyiphthalide can effectively treat cerebral ischemia; however, the mechanisms underlying the effects of dl-3n-butylphthalide on microcirculation disorders following diffuse brain injury remain unclear. In this study, models of diffuse brain injury were established in Sprague-Dawley rats with the vertical impact method. DI-3n-butylphthalide at 80 and 160 mg/kg was given via intraperitoneal injection immediately after diffuse brain injury. Ultrastructural changes in the cerebral cortex were observed using electron microscopy. Cerebral blood flow was measured by laser Doppler flowmetry, vascular density was marked by tannic acid-ferric chloride staining, vascular permeability was es- timated by the Evans blue method, brain water content was measured using the dry-wet method, and rat behavior was measured by motor function and sensory function tests. At 6, 24, 48, and 72 hours after administration of dl-3n-butylphthalide, reduced cerebral ultrastructure damage, in- creased vascular density and cerebral blood flow, and improved motor and sensory functions were observed. Our findings demonstrate that dl-3n-butylphthalide may have protective effects against diffuse brain injury by ameliorating microcirculation disorder and reducing blood-brain barrier dam- age and cerebral edema.展开更多
Blood-brain barrier(BBB)disruption underlies the vasogenic edema and neuronal cell death induced by acute ischemic stroke.Reducing this disruption has therapeutic potential.Transcranial focused ultrasound stimulation ...Blood-brain barrier(BBB)disruption underlies the vasogenic edema and neuronal cell death induced by acute ischemic stroke.Reducing this disruption has therapeutic potential.Transcranial focused ultrasound stimulation has shown neuromodulatory and neuroprotective effects in various brain diseases including ischemic stroke.Ultrasound stimulation can reduce inflammation and promote angiogenesis and neural circuit remodeling.However,its effect on the BBB in the acute phase of ischemic stroke is unknown.In this study of mice subjected to middle cerebral artery occlusion for 90 minutes,low-intensity low-frequency(0.5 MHz)transcranial focused ultrasound stimulation was applied 2,4,and 8 hours after occlusion.Ultrasound stimulation reduced edema volume,improved neurobehavioral outcomes,improved BBB integrity(enhanced tight junction protein ZO-1 expression and reduced IgG leakage),and reduced secretion of the inflammatory factors tumor necrosis factor-αand activation of matrix metalloproteinase-9 in the ischemic brain.Our results show that low-intensity ultrasound stimulation attenuated BBB disruption and edema formation,which suggests it may have therapeutic use in ischemic brain disease as a protector of BBB integrity.展开更多
基金Supported by High Technology Fund of Japanese Ministry of Education,Culture,Sports,Science and Technology:Clinical and Experimental Research on the Influence of Acupuncture and Chinese Medicine Herb on Recovery of Nerve Ending Damage(No.343) Open Fund Key Projects of Zhejiang Provincial Top Key Discipline of Acupuncture and Massage(No.ZTK2010A07)
文摘OBJECTIVE:To observe the effects of bloodletting puncture at Jing-Well points in the distal ends of the finger and toe on survival rate,survival time,and brain edema in rats with cerebral ischemia.METHODS:Fifty-four male Sprague-Dawley rats were randomly divided into five groups:normal,sham operation,model,bloodletting puncture at Jing-Well points in distal ends of finger and toe,and puncture without bloodletting at these points.Middle cerebral artery occlusion models were established according to Longa's method.The brains were taken 48 h after the model was established.Brain water content,brain density,brain coefficient,survival rate,and survival time in each group were measured.RESULTS:After bloodletting puncture,the survival time of the rats was prolonged,their brain water content and brain coefficient were reduced,and brain density was increased.CONCLUSION:Bloodletting puncture at Jing-Well points in the distal ends of the finger and toe can improve function in ischemic brain edema.
文摘Intracranial hypertension is a major cause of morbidity and mortality of patients suffering from fulminant hepatic failure. The etiology of this intracranial hypertension is not fully determined, and is probably multifactorial, combining a cytotoxic brain edema due to the astrocytic accumulation of glutamine, and an increase in cerebral blood volume and cerebral blood flow, in part due to inflammation, to glutamine and to toxic products of the diseased liver. Validated methods to control intracranial hypertension in fulminant hepatic failure patients mainly include mannitol, hypertonic saline, indomethacin, thiopental, and hyperventilation. However all these measures are often not sufficient in absence of liver transplantation, the only curative treatment of intracranial hypertension in fulminant hepatic failure to date. Induced moderate hypothermia seems very promising in this setting, but has to be validated by a controlled, randomized study. Artificial liver support systems have been under investigation for many decades. The bioartiflcial liver, based on both detoxification and swine liver cells, has shown some efficacy on reduction of intracranial pressure but did not show survival benefit in a controlled, randomized study. The Molecular Adsorbents Recirculating System has shown some efficacy in decreasing intracranial pressure in an animal model of liver failure, but has still to be evaluated in a phase Ⅲ trial.
文摘OBJECTIVE： To investigate the relationship of aquaporin 4 （AQP4） and brain edema. DATA SOURCES： Using the terms of ＂aquaporin-4, brain edema＂, we searched PubMed database to identify studies published from January 1997 to April 2006 in the English languages. Meanwhile, we also searched China National Knowledge Infrastructure （CNKI） for related studies. STUDY SELECTION： The collected data were selected firstly. Studies on AQP4 and brain edema were chosen and their full-texts were searched for, and those with repetitive or review studies were excluded. DATA EXTRACTION： Totally 146 related studies were collected, 42 of them were involved and the other 104 studies were used for reading reference data. DATA SYNTHESIS： AQP4 is a selective water permeable integral membrane protein. It is mainly expressed in astrocytes and ependymocyte, and is the important structural basis for water regulation and transportation between glial cells and cerebrospinal fluid or vessels. Phosphorylation is involved in the regulation of AQP4. AQP4 participates in the formation of brain edema caused by various factors. Studies on the structure and pathological changes of AQP4 are still in the initial stage, and the role and mechanism of AQP4 in the formation of brain edema is very unclear. CONCLUSION： AQP4 plays a critical regulating role in the formation of ischemic brain edema, but whether it is regulated by drugs lacks reliable evidence.
基金Supported by Grant #TB 56 from the University of Buenos Aires,Argentina
文摘AIM:To study the blood-brain barrier integrity,brain edema, animal behavior and ammonia plasma levels in prehepatic portal hypertensive rats with and without acute liver intoxication. METHODS:Adults male Wistar rats were divided into four groups.Group Ⅰ:sham operation;Ⅱ:Prehepatic portal hypertension,produced by partial portal vein ligation;Ⅲ: Acetaminophen intoxication and Ⅳ:Prehepatic portal hypertension plus acetaminophen.Acetaminophen was administered to produce acute hepatic injury.Portal pressure,liver serum enzymes and ammonia plasma levels were determined.Brain cortex water content was registered and trypan blue was utilized to study blood brain barrier integrity.Reflexes and behavioral tests were recorded. RESULTS:Portal hypertension was significantly elevated in groups Ⅱ and Ⅳ.Uver enzymes and ammonia plasma levels were increased in groups Ⅱ,Ⅲ and Ⅳ.Prehepatic portal hypertension (group Ⅱ),acetaminophen intoxication (group Ⅲ) and both (group Ⅳ) had changes in the blood brain-barrier integrity (trypan blue) and hyperammonemia.Cortical edema was present in rats with acute hepatic injury in groups Ⅲ and Ⅳ.Behavioral test (rota rod) was altered in group Ⅳ. CONCLUSION:These results suggest the possibility of another pathway for cortical edema production because blood brain barrier was altered (vasogenic) and hyperammonemia was registered (oltotoxic).Group Ⅳ,with behavioral altered test,can be considered as a model for study at an early stage of portal-systemic encephalopathy.
基金supported by a grant for Scientific Research Program from the Health Bureau of Henan Province (No.200202)
文摘To investigate the role of AQP9 in brain edema, the expression of AQP9 in an infectious rat brain edema model induced by the injection of lipopolysaccharide （LPS） was examined. Immuno- histochemistry and reverse transcription-polymerase chain reaction （RT-PCR） analysis demonstrated that the expressions of AQP9 mRNA and protein at all observed intervals were significantly increased in LPS-treated animals in comparison with the control animals. Time-course analysis showed that the first signs of blood-brain barrier disruption and the increase of brain water content in LPS-treated animals were evident 6 h after LPS injection, with maximum value appearing at 12 h, which coincided with the expression profiles of AQP9 mRNA and protein in LPS-treated animals. The further correlation analysis revealed strong positive correlations among the brain water content, the disruption of the blood-brain barrier and the enhanced expressions of AQP9 mRNA and protein in LPS-treated animals. These results suggested that the regulation of AQP9 expression may play im- portant roles in water movement and in brain metabolic homeostasis associated with the pathophysi- ology of brain edema induced by LPS injection.
基金supported by the Natural Science Foundation of Guangdong Province,No.10151600101000002
文摘The experimental model of traumatic brain injury was established in Sprague-Dawley rats according to Feeney＇s free falling method. The brains were harvested at 2, 6 and 24 hours, and at 3 and 5 days after injury. Changes in brain water content were determined using the wet and dry weights. Our results showed that water content of tissue significantly increased after traumatic brain injury, and reached minimum at 24 hours. Hematoxylin-eosin staining revealed pathological impairment of brain tissue at each time point after injury, particularly at 3 days, with nerve cell edema, degenera- tion, and necrosis observed, and the apoptotic rate significantly increased. Immunohistochemistry and western blot analysis revealed that the expression of occludin at the injured site gradually de- creased as injury time advanced and reached a minimum at 3 days after injury; the expression of connexin 43 gradually increased as injury time advanced and reached a peak at 24 hours after in-jury. The experimental findings indicate that changes in occludin and connexin 43 expression were consistent with the development of brain edema, and may reflect the pathogenesis of brain injury.
基金Supported by A grant from the Instituto de Salud CarlosTM,PI051371,PI080809
文摘AIM:To compare rifaximin and insulin-like growth factor(IGF)-1 treatment of hyperammonemia and brain edema in cirrhotic rats with portal occlusion.METHODS:Rats with CCl4-induced cirrhosis with ascites plus portal vein occlusion and controls were randomized into six groups:Cirrhosis;Cirrhosis + IGF-1;Cirrhosis + rifaximin;Controls;Controls + IGF-1;and Controls + rifaximin.An oral glutamine-challenge test was performed,and plasma and cerebral ammonia,glucose,bilirubin,transaminases,endotoxemia,brain water content and ileocecal cultures were measured and liver histology was assessed.RESULTS:Rifaximin treatment significantly reduced bacterial overgrowth and endotoxemia compared with cirrhosis groups,and improved some liver function parameters(bilirubin,alanine aminotransferase and aspartate aminotransferase).These effects were associated with a significant reduction in cerebral water content.Blood and cerebral ammonia levels,and area-underthe-curve values for oral glutamine-challenge tests were similar in rifaximin-treated cirrhotic rats and control group animals.By contrast,IGF-1 administration failed to improve most alterations observed in cirrhosis.CONCLUSION:By reducing gut bacterial overgrowth,only rifaximin was capable of normalizing plasma and brain ammonia and thereby abolishing low-grade brain edema,alterations associated with hepatic encephalopathy.
基金National Major Scientific Instruments and Equipment Development Project Funded by National Natural Science Foundation of China(81827803 and 81727804)the National Natural Science Foundation of China(61875085).
文摘Intracranial hypertension is a serious threat to the health of neurosurgical patients.At present,there is a lack of a safe and e®ective technology to monitor intracranial pressure(ICP)accurately and nondestructively.In this paper,based on near infrared technology,the continuous nonde-structive monitoring of ICP change caused by brain edema was studied.The rat brain edema models were constructed by lipopolysaccharide.The ICP monitor and the self-made near infrared tissue parameter measuring instrument were used to monitor the invasive intracranial pressure and the reduced scattering coe±cient of brain tissue during the brain edema development.The results showed that there was a negative correlation between the reduced scattering coe±cient(690nm and 834nm)and ICP,and then the mathematical model was established.The experimental results promoted the development of nondestructive ICP monitoring based on near infrared technology.
文摘BACKGROUND： Stereo-tactic radiation therapy （SRT） is widely used to treat intracranial diseases, but some patients suffered from radiation induced brain edema after SRT. Once radiation induced brain edema occurs, the treatment is quite difficult, and it always leads to a poor outcome. Dexamethasone has certain therapeutic effect on traumatic brain edema, but the biological mechanism is still unclear. OBJECTIVE ： To observe the effect of dexamethasone on the neutrophil expression of CD18.DESIGN ： A randomized control observation.SETTING： Changhai Hospital of the Second Military Medical University of Chinese PLA. MATERIALS ： The experiment was carried out in Changhai Hospital of the Second Military Medical University of Chinese PLA from January 1999 to December 1999. Twenty SD rats （male and female each in half） weighing （250±50） g were used. METHODS： Twenty SD rats were divided into four groups at random. ① Blank control group （n=5）： The rats were not treated without dexamethasone or irradiation;② Irradiation group （n=5）： The rats were given irradiation but no dexamethasone treatment; ③ Irradiation＋1 mg/kg dexamethasone group （n=5）; The rats were treated with irradiation and dexamethasone of 1 mg/kg; ④Irradiation＋5 mg/kg dexamethasone group （n=5）： The rats were treated with irradiation and dexamethasone of 5 mg/kg. The heads of the rats were irradiated with 10 MeV X-ray （30 Gy）, and brain tissue was removed after 2 weeks to observe the pathological changes. Blood samples were taken from the carotid artery, gradient centrifugation was used, and neutrophile layer was obtained, the level of neutrophile expression of CD18 mRNA and quantity of membrane proteins in blood were detected with Northern blot and flow cytometry respectively. MAIN OUTCOME MEASURES： ① Blood cell count; ② Pathological results; ③ level of neutrophile expression of CD18 mRNA and quantity of membrane proteins. RESULTS ： All the 20 SD rats were involved in the analysis of results without deletion. At 2 weeks after irradiation, obvious cell injury could be observed under light microscope. The level of neutrophile expression of CD18 mRNA and quantity of membrane proteins in blood were obviously increased, but the severity of cell injury was relieved in the irradiation＋1 and 5 mg/kg dexamethasone groups, and the CD18 expression was markedly suppressed （P 〈 0.05）, and the suppression was more obvious in the irradiation＋5 mg/kg dexamethasone group than in the irradiation＋1 mg/kg dexamethasone group （P 〈 0.01 ）. CONCLUSION： Dexamethasone can reduce the radiation induced brain edema by inhibiting the expression of CD18.
文摘The present study evaluated the effect of dl-3-n-butylphthalide(NBP) ,a novel brain protective agent, on brain edema in rats following focal ischemia. Edema was induced by occluding the right middle cerebral artery (MCAO).producing permanent focal ischemia in the right cerebral hemisphere,which developed ip-silateral brain edema reproducibly. Edema was assessed 24 h after MCA occlusion by determining the brain water content from wet and dry weight measurements,and the sodium,potassium concentrations with ion-selective electrodes. In this model,NBP at the dose of 80,160 and 240 mg/kg po 15 min after MCAO prevented from brain edema in a dose-dependent manner. A significant reduction of sodium content and an increase in potassium level were observed in all drug-treated groups. It showed that NBP strongly attenuated brain water entry,sodium accumulation and potassium loss. Nimodipine treatment(5mg/kg sc) also reduced brain edema (P<0. 05). The results suggest that a strong anti-edema activity of NBP may play an important role to contribute to the treatment of ischemic damage.
基金General program of Chongqing Natural Science Foundation(No.cstc2019jcyj-msxmx0353)Science and technology program of Banan District of Chongqing(No.018-25)
文摘The aquaporin-4(AQP4)is a highly selective membrane protein.It is important for the body to maintain the water balance between internal and external environment of cells,the studies have found that the abnormal expression of AQP4 is related to the occurrence of many diseases.The cerebral edema is the most common and serious complication of brain trauma,and its pathogenesis is closely related to AQP4.The development of multimodal magnetic resonance imaging(M-MRI)could been provided imaging basis for accurate diagnosis of traumatic brain edema.In recent years,the correlation between AQP4 and M-MRI has become a hotspot of research.This paper reviews the research progress on the correlation between AQP4 expression in traumatic cerebral edema and M-MRI.
文摘Acute traumatic brain edema models were established in SD rats by dropping weight methods.We observed the therapeutic effect of Cyproheptadine(Cyp)on traumatic brain edema.It was shown that Cyp could obviously reduce the brain water content,decrease the releae or LDH,reduce the seventy of the pathological changes at the injury areas,increase the SOD activity and decrease the production of MDA in SD rats.The results suggest that Cyp has obvious.therapeutic effect on traumatic brain edema.The mechanism may be that it can increase the activity or clearance enzyme of free radical,inhibit lipid peroxldation and reduce intracellular Ca2+-overload.
文摘Objective: To determine whether VEGF plays a role in the development of peritumoral brain edema. Methods 50 meningioma patients and their VEGF expression were studied. We took a monoclonal antibody from mouse to VEGF to stain the tumor cells, the vascular endothelial cells and the interstitial cells. The severity of brain edema was evaluated according to CT or MR scans by the following equation: edema index= V tumor +edema /Vtumor. The relationship between VEGF expression and edema index was analyzed statistically. Results VEGF was expressed in meningioma tumor cells, which is usually concentrated at the peripheral sites of the tumor. There was a positive linear correlation between the expression and the brain edema index. Conclusion VEGF may play a role in the development of peritumoral brain edema in meningioma patient.
基金supported by the Natural Science Foundation of Shandong Province,No.ZR2022MH124the Youth Science Foundation of Shandong First Medical University,No.202201–105(both to YX)。
文摘Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter injury.Microglia,which are the key immune cells in the central nervous system,maintain homeostasis in the neural environment,support neurons,mediate apoptosis,participate in immune regulation,and have neuroprotective effects.Increasing evidence has shown that microglia play a pivotal role in the pathogenesis of subarachnoid hemorrhage and affect the process of injury and the prognosis of subarachnoid hemorrhage.Moreover,microglia play certain neuroprotective roles in the recovery phase of subarachnoid hemorrhage.Several approaches aimed at modulating microglia function are believed to attenuate subarachnoid hemorrhage injury.This provides new targets and ideas for the treatment of subarachnoid hemorrhage.However,an in-depth and comprehensive summary of the role of microglia after subarachnoid hemorrhage is still lacking.This review describes the activation of microglia after subarachnoid hemorrhage and their roles in the pathological processes of vasospasm,neuroinflammation,neuronal apoptosis,blood–brain barrier disruption,cerebral edema,and cerebral white matter lesions.It also discusses the neuroprotective roles of microglia during recovery from subarachnoid hemorrhage and therapeutic advances aimed at modulating microglial function after subarachnoid hemorrhage.Currently,microglia in subarachnoid hemorrhage are targeted with TLR inhibitors,nuclear factor-κB and STAT3 pathway inhibitors,glycine/tyrosine kinases,NLRP3 signaling pathway inhibitors,Gasdermin D inhibitors,vincristine receptorαreceptor agonists,ferroptosis inhibitors,genetic modification techniques,stem cell therapies,and traditional Chinese medicine.However,most of these are still being evaluated at the laboratory stage.More clinical studies and data on subarachnoid hemorrhage are required to improve the treatment of subarachnoid hemorrhage.
文摘S.Lehrer and P.H.Rheinstein,“Alignment of Human Aquaporin 4 and fß-Amyloid Proteins May Indicate Involvement of fß-Amyloid in Brain Water Homeostasis and Prevention of Brain Edema,”Chronic Diseases and Translational Medicine 9(2023):177-181.https://doi.org/10.1002/cdt3.64.
文摘Objective:To characterize the expression of aquaporin-4(AQP4),one of the aquaporins(AQPs),in human brainspecimens from patients with traumatic brain injury or brain tumors.Methods:Nineteen hnman brain specimens were obtahledfrom the patients with traumatic brain injury,brain tumors,benign meningioma or early stage hemorrhagic stroke.MRI or CTimaging was used to assess brain edema.Hematoxylin and eosm staining were used to evaluate cell damage,Immunohistochem-istry was used to detect the AQP4 expression.Results:AQP4 expression was increased from 15 h to at least 8 d after injury.AQP4immunoreactivity was strong around astrocytomas,ganglioglioma and metastatic adenocarcinoma.However,AQP4 immunore-activity was only found in the centers of astrocytomas and ganglioglioma,but not in metastatic adenocarcinoma derived from lung.Conclusion:AQP4 expression increases in human brains alter traumatic brain injury,within brain-derived tumors,and aroundbrain tumors.
基金supported by the National Natural Science Foundation of China,No.81330029,81671380the Natural Science Foundation of Tianjin City of China,No.17JCZDJC35900
文摘Traumatic brain injury induces potent inflammatory responses that can exacerbate secondary blood-brain barrier（BBB） disruption, neuronal injury, and neurological dysfunction. Dexmedetomidine is a novel α2-adrenergic receptor agonist that exert protective effects in various central nervous system diseases. The present study was designed to investigate the neuroprotective action of dexmedetomidine in a mouse traumatic brain injury model, and to explore the possible mechanisms. Adult male C57 BL/6 J mice were subjected to controlled cortical impact. After injury, animals received 3 days of consecutive dexmedetomidine therapy（25 μg/kg per day）. The modified neurological severity score was used to assess neurological deficits. The rotarod test was used to evaluate accurate motor coordination and balance. Immunofluorescence was used to determine expression of ionized calcium binding adapter molecule-1, myeloperoxidase, and zonula occluden-1 at the injury site. An enzyme linked immunosorbent assay was used to measure the concentration of interleukin-1β（IL-1β）, tumor necrosis factor α, and IL-6. The dry-wet weight method was used to measure brain water content. The Evans blue dye extravasation assay was used to measure BBB disruption. Western blot assay was used to measure protein expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3（NLRP3）, caspase-1 p20, IL-1β, nuclear factor kappa B（NF-κB） p65, occluding, and zonula occluden-1. Flow cytometry was used to measure cellular apoptosis. Results showed that dexmedetomidine treatment attenuated early neurological dysfunction and brain edema. Further, dexmedetomidine attenuated post-traumatic inflammation, up-regulated tight junction protein expression, and reduced secondary BBB damage and apoptosis. These protective effects were accompanied by down-regulation of the NF-κB and NLRP3 inflammasome pathways. These findings suggest that dexmedetomidine exhibits neuroprotective effects against acute（3 days） post-traumatic inflammatory responses, potentially via suppression of NF-κB and NLRP3 inflammasome activation.
基金funded by the National NaturalScience Foundation of China (Youth), No. 81001556
文摘This study used electroacupuncture at Renzhong （DU26） and Baihui （DU20） in a rat model of cerebral ischemia/reperfusion injury. Neurological deficit scores, western blotting, and reverse transcription-PCR results demonstrated that electroacupuncture markedly reduced neurological deficits, decreased corpus striatum aquaporin-4 protein and mRNA expression, and relieved damage to the blood-brain barrier in a rat model of cerebral ischemia/reperfusion injury. These results suggest that electroacupuncture most likely protects the blood-brain barrier by regulating aquaporin-4 expression following cerebral ischemia/reperfusion injury.
基金supported by the grants from Hebei Province Science and Technology Ministry,No.20276102DKey Project of Hebei Province Education Ministry,No.ZD2010106
文摘DI-3n-butyiphthalide can effectively treat cerebral ischemia; however, the mechanisms underlying the effects of dl-3n-butylphthalide on microcirculation disorders following diffuse brain injury remain unclear. In this study, models of diffuse brain injury were established in Sprague-Dawley rats with the vertical impact method. DI-3n-butylphthalide at 80 and 160 mg/kg was given via intraperitoneal injection immediately after diffuse brain injury. Ultrastructural changes in the cerebral cortex were observed using electron microscopy. Cerebral blood flow was measured by laser Doppler flowmetry, vascular density was marked by tannic acid-ferric chloride staining, vascular permeability was es- timated by the Evans blue method, brain water content was measured using the dry-wet method, and rat behavior was measured by motor function and sensory function tests. At 6, 24, 48, and 72 hours after administration of dl-3n-butylphthalide, reduced cerebral ultrastructure damage, in- creased vascular density and cerebral blood flow, and improved motor and sensory functions were observed. Our findings demonstrate that dl-3n-butylphthalide may have protective effects against diffuse brain injury by ameliorating microcirculation disorder and reducing blood-brain barrier dam- age and cerebral edema.
基金supported by the National Natural Science Foundation of China,Nos.81802232(to JXW),81801170(to YHT),82071284(to YHT),2019YFA0112000(to YHT)the Scientific Research and Innovation Program of Shanghai Education Commission,No.2019-01-07-00-02-E00064(to GYY)+1 种基金Scientific and Technological Innovation Act Program of Shanghai Science and Technology Commission,No.20JC1411900(to GYY)Science and Technology Commission of Shanghai,No.19441907900(to JFS).
文摘Blood-brain barrier(BBB)disruption underlies the vasogenic edema and neuronal cell death induced by acute ischemic stroke.Reducing this disruption has therapeutic potential.Transcranial focused ultrasound stimulation has shown neuromodulatory and neuroprotective effects in various brain diseases including ischemic stroke.Ultrasound stimulation can reduce inflammation and promote angiogenesis and neural circuit remodeling.However,its effect on the BBB in the acute phase of ischemic stroke is unknown.In this study of mice subjected to middle cerebral artery occlusion for 90 minutes,low-intensity low-frequency(0.5 MHz)transcranial focused ultrasound stimulation was applied 2,4,and 8 hours after occlusion.Ultrasound stimulation reduced edema volume,improved neurobehavioral outcomes,improved BBB integrity(enhanced tight junction protein ZO-1 expression and reduced IgG leakage),and reduced secretion of the inflammatory factors tumor necrosis factor-αand activation of matrix metalloproteinase-9 in the ischemic brain.Our results show that low-intensity ultrasound stimulation attenuated BBB disruption and edema formation,which suggests it may have therapeutic use in ischemic brain disease as a protector of BBB integrity.
