Hydroxysafflor yellow A （HSYA） has angiogenesis- regulating and neuro-protective effects, but its effects on vascular dementia （VaD） are unknown. In this study, 30 adult Sprague-Dawley rats were. randomly allocate...Hydroxysafflor yellow A （HSYA） has angiogenesis- regulating and neuro-protective effects, but its effects on vascular dementia （VaD） are unknown. In this study, 30 adult Sprague-Dawley rats were. randomly allocated to five groups： normal, sham-operation, VaD alone （bilateral carotid artery occlusion）, VaD plus saline （control）, and VaD plus HSYA. One week after operation, the HSYA group received one daily tail-vein injection of 0.6 mg/100 g HSYA for two weeks. Five weeks after operation, the spatial memory of all five groups was evaluated by the water maze task, and synaptic plasticity in the hippocampus was assessed by the long-term potentiation （LTP） method. Vascular endothelial growth factor （VEGF） and N-methyi-D- aspartic acid receptor 1 （NR1） expression in the hippocampus was detected via Western blot. We found that, compared with the group with VaD alone, the group with HSYA had a reduced escape latency in the water maze （P 〈0.05）, and the LTP at CA3- CA1 synapses in the hippocampus was enhanced （P 〈0.05）. Western blot in the late-phase VaD group showed slight up-regulation of VEGF and down- regulation of NR1 in the hippocampus, while HSYA significantly up-regulated both VEGF and NRI. These results suggested that HSYA promotes angiogenesis and increases synaptic plasticity, thus improving spatial learning and memory in the rat model of VaD.展开更多
The rat high-impact free weight drop model mimics the diffuse axonal injury caused by severe traumatic brain injury in humans,while severe controlled cortical impact can produce a severe traumatic brain injury model u...The rat high-impact free weight drop model mimics the diffuse axonal injury caused by severe traumatic brain injury in humans,while severe controlled cortical impact can produce a severe traumatic brain injury model using precise strike parameters.In this study,we compare the pathological mechanisms and pathological changes between two rat severe brain injury models to identify the similarities and differences.The severe controlled cortical impact model was produced by an electronic controlled cortical impact device,while the severe free weight drop model was produced by dropping a 500 g free weight from a height of 1.8 m through a plastic tube.Body temperature and mortality were recorded,and neurological deficits were assessed with the modified neurological severity score.Brain edema and bloodbrain barrier damage were evaluated by assessing brain water content and Evans blue extravasation.In addition,a cytokine array kit was used to detect inflammatory cytokines.Neuronal apoptosis in the brain and brainstem was quantified by immunofluorescence staining.Both the severe controlled cortical impact and severe free weight drop models exhibited significant neurological impairments and body temperature fluctuations.More severe motor dysfunction was observed in the severe controlled cortical impact model,while more severe cognitive dysfunction was observed in the severe free weight drop model.Brain edema,inflammatory cytokine changes and cortical neuronal apoptosis were more substantial and blood-brain barrier damage was more focal in the severe controlled cortical impact group compared with the severe free weight drop group.The severe free weight drop model presented with more significant apoptosis in the brainstem and diffused blood-brain barrier damage,with higher mortality and lower repeatability compared with the severe controlled cortical impact group.Severe brainstem damage was not found in the severe controlled cortical impact model.These results indicate that the severe controlled cortical impact model is relatively more stable,more reproducible,and shows obvious cerebral pathological changes at an earlier stage.Therefore,the severe controlled cortical impact model is likely more suitable for studies on severe focal traumatic brain injury,while the severe free weight drop model may be more apt for studies on diffuse axonal injury.All experimental procedures were approved by the Ethics Committee of Animal Experiments of Tianjin Medical University,China(approval No.IRB2012-028-02)in Febru ary 2012.展开更多
Hyperglycemia reduces the number of circulating endothelial progenitor cells, accelerates their senescence and impairs their function.However, the relationship between blood glucose levels and endothelial progenitor c...Hyperglycemia reduces the number of circulating endothelial progenitor cells, accelerates their senescence and impairs their function.However, the relationship between blood glucose levels and endothelial progenitor cells in peripheral blood of patients with traumatic brain injury is unclear. In this study, 101 traumatic brain injury patients admitted to the Department of Neurosurgery, Tianjin Medical University General Hospital or the Department of Neurosurgery, Tianjin Huanhu Hospital, China, were enrolled from April 2005 to March 2007. The number of circulating endothelial progenitor cells and blood glucose levels were measured at 1, 4, 7, 14 and 21 days after traumatic brain injury by flow cytometry and automatic biochemical analysis, respectively. The number of circulating endothelial progenitor cells and blood sugar levels in 37 healthy control subjects were also examined. Compared with controls, the number of circulating endothelial progenitor cells in traumatic brain injury patients was decreased at 1 day after injury, and then increased at 4 days after injury,and reached a peak at 7 days after injury. Compared with controls, blood glucose levels in traumatic brain injury patients peaked at 1 day and then decreased until 7 days and then remained stable. At 1, 4, and 7 days after injury, the number of circulating endothelial progenitor cells was negatively correlated with blood sugar levels(r =-0.147, P < 0.05). Our results verify that hyperglycemia in patients with traumatic brain injury is associated with decreased numbers of circulating endothelial progenitor cells. This study was approved by the Ethical Committee of Tianjin Medical University General Hospital, China(approval No. 200501) in January 2015.展开更多
Traumatic brain injury（TBI） can result in poor functional outcomes and death, and overall outcomes are varied. Growth factors, such as angiopoietin-1（Ang-1）, vascular endothelial growth factor（VEGF）, and granulo...Traumatic brain injury（TBI） can result in poor functional outcomes and death, and overall outcomes are varied. Growth factors, such as angiopoietin-1（Ang-1）, vascular endothelial growth factor（VEGF）, and granulocyte-colony stimulating factor（G-CSF）, play important roles in the neurological functions. This study investigated the relationship between serum growth factor levels and long-term outcomes after TBI. Blood samples from 55 patients were collected at 1, 3 and 7 days after TBI. Blood samples from 39 healthy controls were collected as a control group. Serum Ang-1, G-CSF, and VEGF levels were measured using ELISA. Patients were monitored for 3 months using the Glasgow Outcome Scale-Extended（GOSE）. Patients having a GOSE score of 〉 5 at 3 months were categorized as a good outcome, and patients with a GOSE score of 1-5 were categorized as a bad outcome. Our data demonstrated that TBI patients showed significantly increased growth factor levels within 7 days compared with healthy controls. Serum levels of Ang-1 at 1 and 7 days and G-CSF levels at 7 days were significantly higher in patients with good outcomes than in patients with poor outcomes. VEGF levels at 7 days were remarkably higher in patients with poor outcomes than in patients with good outcomes. Receiver operating characteristic analysis showed that the best cut-off points of serum growth factor levels at 7 days to predict functional outcome were 1,333 pg/mL for VEGF, 447.2 pg/mL for G-CSF, and 90.6 ng/mL for Ang-1. These data suggest that patients with elevated levels of serum Ang-1, G-CSF, and decreased VEGF levels had a better prognosis in the acute phase of TBI（within 7 days）. This study was registered with the Chinese Clinical Trial Registry（registration number： ChiCTR1800018251） on September 7, 2018.展开更多
A moderate stress such as cold water swimming can raise the tolerance of the body to potentially injurious events. However, little is known about the mechanism of beneficial effects induced by moderate stress. In this...A moderate stress such as cold water swimming can raise the tolerance of the body to potentially injurious events. However, little is known about the mechanism of beneficial effects induced by moderate stress. In this study, we used a classic rat model of traumatic brain injury to test the hypothesis that cold water swimming preconditioning improved the recovery of cognitive functions and explored the mechanisms. Results showed that after traumatic brain injury, pre-conditioned rats（cold water swimming for 3 minutes at 4℃） spent a significantly higher percent of times in the goal quadrant of cold water swim, and escape latencies were shorter than for non-pretreated rats. The number of circulating endothelial progenitor cells was significantly higher in pre-conditioned rats than those without pretreatment at 0, 3, 6 and 24 hours after traumatic brain injury. Immunohistochemical staining and Von Willebrand factor staining demonstrated that the number of CD34~＋ stem cells and new blood vessels in the injured hippocampus tissue increased significantly in pre-conditioned rats. These data suggest that pretreatment with cold water swimming could promote the proliferation of endothelial progenitor cells and angiogenesis in the peripheral blood and hippocampus. It also ameliorated cognitive deficits caused by experimental traumatic brain injury.展开更多
Hypothalamic-pituitary-adrenal axis dysfunction may lead to the occurrence of critical illness-related corticosteroid insufficiency.Critical illness-related corticosteroid insufficiency can easily occur after traumati...Hypothalamic-pituitary-adrenal axis dysfunction may lead to the occurrence of critical illness-related corticosteroid insufficiency.Critical illness-related corticosteroid insufficiency can easily occur after traumatic brain injury,but few studies have examined this occurrence.A multicenter,prospective,cohort study was performed to evaluate the function of the hypothalamic-pituitary-adrenal axis and the incidence of critical illness-related corticosteroid insufficiency during the sub-acute phase of traumatic brain injury.One hundred and forty patients with acute traumatic brain injury were enrolled from the neurosurgical departments of three tertiary-level hospitals in China,and the critical illness-related corticosteroid insufficiency incidence,critical-illness-related corticosteroid insufficiency-related risk factors,complications,and 28-day mortality among these patients was recorded.Critical illness-related corticosteroid insufficiency was diagnosed in patients with plasma total cortisol levels less than 10μg/dL(275.9 nM)on post-injury day 4 or when serum cortisol was insufficiently suppressed(less than 50%)during a dexamethasone suppression test on post-injury day 5.The results demonstrated that critical illness-related corticosteroid insufficiency occurred during the sub-acute phase of traumatic brain injury in 5.6%of patients with mild injury,22.5%of patients with moderate injury,and 52.2%of patients with severe injury.Traumatic brain injury-induced critical illness-related corticosteroid insufficiency was strongly correlated to injury severity during the sub-acute stage of traumatic brain injury.Traumatic brain injury patients with critical illness-related corticosteroid insufficiency frequently presented with hemorrhagic cerebral contusions,diffuse axonal injury,brain herniation,and hypotension.Differences in the incidence of hospital-acquired pneumonia,gastrointestinal bleeding,and 28-day mortality were observed between patients with and without critical illness-related corticosteroid insufficiency during the sub-acute phase of traumatic brain injury.Hypotension,brain-injury severity,and the types of traumatic brain injury were independent risk factors for traumatic brain injury-induced critical illness-related corticosteroid insufficiency.These findings indicate that critical illness-related corticosteroid insufficiency is common during the sub-acute phase of traumatic brain injury and is strongly associated with poor prognosis.The dexamethasone suppression test is a practical assay for the evaluation of hypothalamic-pituitary-adrenal axis function and for the diagnosis of critical illness-related corticosteroid insufficiency in patients with traumatic brain injury,especially those with hypotension,hemorrhagic cerebral contusions,diffuse axonal injury,and brain herniation.Sub-acute infection of acute traumatic brain injury may be an important factor associated with the occurrence and development of critical illness-related corticosteroid insufficiency.This study protocol was approved by the Ethics Committee of General Hospital of Tianjin Medical University,China in December 2011(approval No.201189).展开更多
Traumatic brain injury can cause loss of neuronal tissue, remote symptomatic epilepsy, and cognitive deficits. However, the mechanisms underlying the effects of traumatic brain injury are not yet clear. Hippocampal ex...Traumatic brain injury can cause loss of neuronal tissue, remote symptomatic epilepsy, and cognitive deficits. However, the mechanisms underlying the effects of traumatic brain injury are not yet clear. Hippocampal excitability is strongly correlated with cognitive dysfunction and remote symptomatic epilepsy. In this study, we examined the relationship between traumatic brain injury-induced neuronal loss and subsequent hippocampal regional excitability. We used hydraulic percussion to generate a rat model of traumatic brain injury. At 7 days after injury, the mean modified neurological severity score was 9.5, suggesting that the neurological function of the rats was remarkably impaired. Electrophysiology and immunocytochemical staining revealed increases in the slope of excitatory postsynaptic potentials and long-term depression（indicating weakened long-term inhibition）, and the numbers of cholecystokinin and parvalbumin immunoreactive cells were clearly reduced in the rat hippocampal dentate gyrus. These results indicate that interneuronal loss and changes in excitability occurred in the hippocampal dentate gyrus. Thus, traumatic brain injury-induced loss of interneurons appears to be associated with reduced long-term depression in the hippocampal dentate gyrus.展开更多
Fluid percussion-induced traumatic brain injury models have been widely used in experimental research for years. In an experiment, the stability of impaction is inevitably affected by factors such as the appearance of...Fluid percussion-induced traumatic brain injury models have been widely used in experimental research for years. In an experiment, the stability of impaction is inevitably affected by factors such as the appearance of liquid spikes. Management of impact pressure is a crucial factor that determines the stability of these models, and direction of impact control is another basic element. To improve experimental stability, we calculated a pressure curve by generating repeated impacts using a fluid percussion device at different pendulum angles. A stereotactic frame was used to control the direction of impact. We produced stable and reproducible models, including mild, moderate, and severe traumatic brain injury, using the MODEL01-B device at pendulum angles of 6°, 11° and 13°, with corresponding impact force values of 1.0 ± 0.11 atm（101.32 ± 11.16 k Pa）, 2.6 ± 0.16 atm（263.44 ± 16.21 k Pa）, and 3.6 ± 0.16 atm（364.77 ± 16.21 k Pa）, respectively. Behavioral tests, hematoxylin-eosin staining, and magnetic resonance imaging revealed that models for different degrees of injury were consistent with the clinical properties of mild, moderate, and severe craniocerebral injuries. Using this method, we established fluid percussion models for different degrees of injury and stabilized pathological features based on precise power and direction control.展开更多
The matrix-degrading metalloproteinases （MMPs）, particularly MMP-9, play important roles in the pathogenesis and development of malignant gliomas. In the present study, the oncogenic role of MMP-9 in malignant gliom...The matrix-degrading metalloproteinases （MMPs）, particularly MMP-9, play important roles in the pathogenesis and development of malignant gliomas. In the present study, the oncogenic role of MMP-9 in malignant glioma cells was investigated via antisense RNA blockade in vitro and in vivo. TJ905 malignant glioma cells were transfected with pcDNA3.0 vector expressing antisense MMP-9 RNA （pcDNA-AS-MMP9）, which significantly decreased MMP-9 expression, and cell proliferation was assessed. For in vivo studies, U251 cells, a human malignant glioma cell line, were implanted subcutaneously into 4-to 6-week-old BALB/c nude mice. The mice bearing well-established U251 gliomas were treated with intratumoral pcDNA-AS-MMP9-Lipofectamine complex （AS-MMP-9-treated group）, subcutaneous injection of endostatin （endostatin-treated group）, or both （combined therapy group）. Mice treated with pcDNA （empty vector）-Lipofectamine served as the control group. Four or eight weeks later, the volume and weight of tumor, MMP-9 expression, microvessel density and proliferative activity were assayed. We demonstrate that pcDNA-AS-MMP9 significantly decreased MMP-9 expression and inhibited glioma cell proliferation. Volume and weight of tumor, MMP-9 expression, microvessel density and proliferative activity in the antisense-MMP-9-treated and therapeutic alliance groups were significantly lower than those in the control group. The results suggest that MMP-9 not only promotes malignant glioma cell invasiveness, but also affects tumor cell proliferation. Blocking the expression of MMP-9 with antisense RNA substantially suppresses the malignant phenotype of glioma cells, and thus can be used as an effective therapeutic strategy for malignant gliomas.展开更多
Neutrophil extracellular traps are primarily composed of DNA and histones and are released by neutrophils to promote inflammation and thrombosis when stimulated by various inflammato ry reactions.Neutrophil extracellu...Neutrophil extracellular traps are primarily composed of DNA and histones and are released by neutrophils to promote inflammation and thrombosis when stimulated by various inflammato ry reactions.Neutrophil extracellular trap formation occurs through lytic and non-lytic pathways that can be further classified by formation mechanisms.Histones,von Willebrand factor,fibrin,and many other factors participate in the interplay between inflammation and thrombosis.Neuroimmunothrombosis summarizes the intricate interplay between inflammation and thrombosis during neural development and the pathogenesis of neurological diseases,providing cutting-edge insights into post-neurotrauma thrombotic events.The blood-brain barrier defends the brain and spinal cord against external assaults,and neutrophil extracellular trap involvement in blood-brain barrier disruption and immunothrombosis contributes substantially to secondary injuries in neurological diseases.Further research is needed to understand how neutrophil extracellular traps promote blood-brain barrier disruption and immunothrombosis,but recent studies have demonstrated that neutrophil extracellular traps play a crucial role in immunothrombosis,and identified modulators of neuro-immunothrombosis.However,these neurological diseases occur in blood vessels,and the mechanisms are unclear by which neutrophil extracellular traps penetrate the blood-brain barrier to participate in immunothrombosis in traumatic brain injury.This review discusses the role of neutrophil extracellular traps in neuro-immunothrombosis and explores potential therapeutic interventions to modulate neutrophil extracellular traps that may reduce immunothrombosis and improve traumatic brain injury outcomes.展开更多
BACKGROUND：Endogenous neural progenitor cells play a beneficial role for cognitive recovery following traumatic brain injury.However,there are few classification-control studies aimed at varying graded brain trauma.O...BACKGROUND：Endogenous neural progenitor cells play a beneficial role for cognitive recovery following traumatic brain injury.However,there are few classification-control studies aimed at varying graded brain trauma.OBJECTIVE：To observe the effects of adult endogenous neurogenesis on cognitive function repair and regeneration of neural progenitor cells following varying graded traumatic hippocampal injury to determine the significance of endogenous neurogenesis in the repair of brain injury.DESIGN,TIME AND SETTING：A randomized,controlled,animal experiment was performed at the Key Laboratory of Injuries,Variations and Regeneration of Nervous System,Tianjin Medical University General Hospital,from February to October 2009.MATERIALS：Mouse anti-rat 5-bromodeoxyuridine （BrdU） and neuronal nuclei （NeuN） monoclonal antibodies were purchased from Millipore Corporation,USA.METHODS：A total of 45 Wistar rats were randomly assigned to three groups.Mild and severe injury groups were respectively subjected to （182 ± 2） kPa and （284 ± 4） kPa lateral fluid percussion to establish models of brain injury,and the control group was subjected to surgery with no lateral fluid percussion.MAIN OUTCOME MEASURES：Cognitive function was estimated using the Morris water maze.Proliferation,survival,and differentiation of newly generated cells in the injured hippocampus were observed through the use of immunofluorescent staining.RESULTS：At 7 days post-injury,the number of BrdU＋ cells in the hippocampal dentate gyrus significantly increased in the mild and severe injury groups compared with the control group （P〈0.01）.At 61 days post-injury,the number of BrdU7NeuN＋ cells in the hippocampal dentate gyrus was significantly greater in the mild injury group compared with the severe injury and control groups （P〈 0.01）.In addition,the control group exhibited the greatest proportion of surviving cells that differentiated into mature neurons compared with the injury groups （P〈 0.01）.Moreover,at 61 days post-injury,cognitive function in rats with mild injury recovered to normal levels,whereas the severe injury group exhibited cognitive deficits （P〈 0.01）.CONCLUSION：Traumatic brain injury may be a stimulation factor for proliferation of neural progenitor cells in the adult hippocampus but severe brain trauma does not lead to an increased number of newly generated cells.Endogenous adult neurogenesis repairs neurological functions to an extent.However,recovery of neurological function remains limited following severe traumatic brain injury.展开更多
Background Traumatic brain injury （TBI） is a heterogeneous condition that can lead to critical LLLness-related corticosteroid insufficiency （CIRCI） causing a high mortality and morbidity.Glucocorticoids were widel...Background Traumatic brain injury （TBI） is a heterogeneous condition that can lead to critical LLLness-related corticosteroid insufficiency （CIRCI） causing a high mortality and morbidity.Glucocorticoids were widely used in the clinical management of TBI,but their benefit has been challenged in some studies and their efficacy,especially for treating CIRCI in TBI patients,remains unclear.Methods We conducted a meta-analysis of published data to determine if the controversy is related to clinical dosing and timing of glucocorticoids （GCs） application.We analyzed published reports in four databases （MEDLINE,EMBASE,the Cochrane Controlled Trials Register,and CBMdisc）.The published data were stratified into not only low-and high-dose GCs group but also short-and long-term GCs group to compare their effectiveness in improving TBI outcomes.Results We totally identified 16 reports.For low-dose patients,the pooled relative risks （RRs） for two clinical outcomes of death or a combination of death and severe disability were 0.95 （95% confidence interval （CI）：0.80 to 1.13） and 0.95 （95% CI：0.83 to 1.09）,respectively.The risks for infection and gastrointestinal bleeding were 0.85 （95% CI：0.50 to 1.45） and 0.64 （95% Cl：0.15 to 2.70）,respectively.For high-dose group,the pooled RR of death is 1.14 （95% Cl：1.06 to 1.21）.The pooled RRs for infection and gastrointestinal bleeding for the high-dose patients were 1.04 （95% CI：0.93 to 1.15） and 1.26 （95% CI：0.92 to 1.75）,respectively.For long-term use group,the pooled RRs for two clinical outcomes of death or a combination of death and severe disability were 0.98 （95% CI：0.87 to 1.12） and 1.00 （95% CI：0.90 to 1.11）,respectively.The risks for infection and gastrointestinal bleeding were 0.88 （95% CI：0.71 to 1.11） and 0.96 （95% CI：0.35 to 2.66）,respectively.For short-term use group,the pooled RR of death is 1.15 （95% CI：1.07 to 1.23）,and importantly the effects on infections were beneficial in terms of TBI patients suffering from CIRCI.Conclusions This meta-analysis suggests an increased risk of death for TBI patients on a high dose and short term of glucocorticoids compared with those on a low dose and long term,for whom a trend towards clinical improvement is evident.In addition,stress-does of GCs further decrease the pneumonia incidence in TBI patients suffering from CIRCI.A large-scale multicenter randomized controlled trial is warranted for testing （1） the efficacy of stress-dose GCs treatment in the sub-acute phase of TBI （4-21 days after initial trauma）,when CIRCI is most likely to occur; （2） the hypothesis that stress-dose GCs could boost patients＇ stress function and ensure survival.展开更多
Chronic subdural hematoma(CSDH)is a chronic space-occupying lesion formed by blood accumulation between arachnoid and dura mater,which is usually formed in the third week after traumatic brain injury.Surgical treatmen...Chronic subdural hematoma(CSDH)is a chronic space-occupying lesion formed by blood accumulation between arachnoid and dura mater,which is usually formed in the third week after traumatic brain injury.Surgical treatment is usually the first choice for patients with CSDH having a significant space-occupying effect.Most of the patients showed good results of surgical treatment,but still some patients had a postoperative recurrence(the recurrence rate was up to 33%).Because CSDH is often seen in the elderly,patients are weak and have many basic diseases.The risk of surgical treatment is high;serious complications and even death(the death rate is up to 32%)can often occur.The overall good prognosis rate of patients aged more than 90 years is 24%.The drug treatment can provide a safe and effective treatment for elderly patients who are weak,intolerable to surgery,or failed in surgery.Low-dose and long-term use of atorvastatin(20mg/d)is suggested for continuous treatment for at least 8 weeks,while low-dose and short-term use of dexamethasone can improve the therapeutic effect of atorvastatin on CSDH.Patients should undergo CT or MRI scanning at least one time within 2 weeks after the start of drug treatment.展开更多
Background::Extra-corporeal video telescope operating monitor system provides a necessary instrument to perform high-precision neurosurgical procedures that could substitute or supplement the traditional surgical micr...Background::Extra-corporeal video telescope operating monitor system provides a necessary instrument to perform high-precision neurosurgical procedures that could substitute or supplement the traditional surgical microscope.The present study was designed to evaluate a compact high-definition two-dimensional exoscope system for assisting in surgical removal of large vestibular schwannoma(VS),as an alternative to a binocular surgical microscope.Methods::Patients with Koos grade 3 and grade 4 VS undergoing surgery were enrolled in this prospective cohort study between January 2013 and June 2018.The demographics and tumor characteristics(size,Koos grade,composition[cystic or solid mass])were matched between the two groups of patients.The following outcome measurements were compared between the two groups:duration of surgery,volume of blood loss,extent of tumor resection,number of operating field adjustments,pre-and post-operative facial and cochlear nerve function evaluated at 3 months post-surgery,complications and surgeons’comfortability.Results::A total of 81 patients received tumor resection through the retrosigmoid approach under either an exoscope(cases,n=39)or a surgical microscope(control,n=42).Patients in the two groups had comparable tumor location(P=0.439),Koos grading(P=0.867),and composition(P=0.891).While no significant differences in the duration of surgery(P=0.172),extent of tumor resection(P=0.858),facial function(P=0.838),and hearing ability(P=1.000),patients operated on under an exoscope had less blood loss(P=0.036)and a fewer field adjustments(P<0.001).Both primary and assistant surgeons reported a high level of comfort operating under the exoscope(P=0.001 and P<0.001,respectively).Conclusions::The compact high-definition two-dimensional exoscope system provides a safe and efficient means to assist in removing large VSs,as compared to a surgical microscope.After the acquaintance with a visual perception through a dynamic hint and stereoscopically viewing corresponding to the motion parallax,the exoscope system provided a comfortable,high-resolution visualization without compromising operational efficiency and patient safety.展开更多
Brain ischemia is the second leading cause of death and the third leading cause of disability in the world.Systemic delivery of microRNA,a class of molecules that regulate the expression of cellular proteins associate...Brain ischemia is the second leading cause of death and the third leading cause of disability in the world.Systemic delivery of microRNA,a class of molecules that regulate the expression of cellular proteins associated with angiogenesis,cell growth,proliferation and differentiation,holds great promise for the treatment of brain ischemia.However,their therapeutic efficacy has been hampered by poor delivery efficiency of microRNA.We report herein a platform technology based on microRNA nanocapsules,which enables their effective delivery to the disease sites in the brain.Exemplified by microRNA-21,intravenous injection of the nanocapsules into a rat model of cerebral ischemia could effectively ameliorate the infarct volume,neurological deficit and histopathological severity.展开更多
Background Traumatic brain injury （TBI） often causes cognitive deficits and remote symptomatic epilepsy. Hippocampal regional excitability is associated with the cognitive function. However, little is known about in...Background Traumatic brain injury （TBI） often causes cognitive deficits and remote symptomatic epilepsy. Hippocampal regional excitability is associated with the cognitive function. However, little is known about injury-induced neuronal loss and subsequent alterations of hippocampal regional excitability. The present study was designed to determine whether TBI may impair the cellular circuit in the hippocampus.Methods Forty male Wistar rats were randomized into control （n=-20） and TBI groups （n=20）. Long-term potentiation, extracellular input/output curves, and hippocampal parvalbumin-immunoreactive and cholecystokinin-immunoreactive interneurons were compared between the two groups.Results TBI resulted in a significantly increased excitability in the dentate gyrus （DG）, but a significantly decreased excitability in the cornu ammonis 1 （CA1） area. Using design-based stereological injury procedures, we induced interneuronal loss in the DG and CA3 subregions in the hippocampus, but not in the CA1 area. Conclusions TBl leads to the impairment of hippocampus synaptic plasticity due to the changing of interneuronal interaction. The injury-induced disruption of synaptic efficacy within the hippocampal circuit may underlie the observed cognitive deficits and symptomatic epilepsy.展开更多
Background Endothelial dysfunction is thought to be critical events in the pathogenesis of Alzheimer＇s disease （AD）.Endothelial progenitor cells （EPCs） have provided insight into maintaining and repairing endothe...Background Endothelial dysfunction is thought to be critical events in the pathogenesis of Alzheimer＇s disease （AD）.Endothelial progenitor cells （EPCs） have provided insight into maintaining and repairing endothelial function. To study the relation between EPCs and AD, we explored the number of circulating EPCs in patients with AD.Methods A total of 104 patients were recruited from both the outpatients and inpatients of the geriatric neurology department at General Hospital, rianjin Medical University. Consecutive patients with newly diagnosed AD （n=30）,patients with vascular dementia （VaD, n=34）, and healthy elderly control subjects with normal cognition （n=40） were enrolled after matching for age, gender, body mass index, medical history, current medication and Mini Mental State Examination. Middle cerebral artery flow velocity was examined with transcranial Doppler. Endothelial function was evaluated according to the level of EPCs, and peripheral blood EPCs was counted by flow cytometry.Results There were no significant statistical differences of clinical data in AD, VaD and control groups （P 〉0.05）. The patients with AD showed decreased CD34-positive （CD34＋） or CD133-positive （CD133＋） levels compared to the control subjects, but there were no significant statistical differences in patients with AD. The patients with AD had significantly lower CD34＋CD133＋ EPCs（CD34 and CD133 double positive endothelial progenitor cells） than the control subjects （P 〈0.05）. In the patients with AD, a lower CD34＋CD133＋ EPCs count was independently associated with a lower Mini-Mental State Examination score （r=0.514, P=0.004）. Patients with VaD also showed a significant decrease in CD34＋CD133＋ EPCs levels, but this was not evidently associated with the Mini-Mental State Examination score. The changes of middle cerebral artery flow velocity were similar between AD and VaD. Middle cerebral artery flow velocity was decreased in the AD and VaD groups and significantly lower than the normal control group （P 〈0.01）. There was no significant difference of the blood flow velocity between the AD and VaD patients （P 〉0.05）.Conclusions The results provided evidence that patients with AD have reduced circulating EPCs. Endothelial function is impaired in patients with AD and vascular factors have a role in the pathogenesis of AD. CD34＋CD133＋ EPCs may be a novel biomarker of AD dementia.展开更多
Traumatic brain injury （TBI） is a major cause of mortality and morbidity in the world. Recent clinical investigations and basic researches suggest that strategies to improve angiogenesis following TBI may provide pr...Traumatic brain injury （TBI） is a major cause of mortality and morbidity in the world. Recent clinical investigations and basic researches suggest that strategies to improve angiogenesis following TBI may provide promising opportunities to improve clinical outcomes and brain functional recovery. More and more evidences show that circulating endothelial progenitor cells （EPCs）, which have been identified in the peripheral blood, may play an important role in the pathologic and physiological anglo-genesis in adults. Moreover, impressive data demonstrate that EPCs are mobilized from bone marrow to blood circula- tion in response to traumatic or inflammatory stimulations. In this review, we discussed the role of EPCs in the repair of brain injury and the possible therapeutic implication for func- tional recovery of TBI in the future.展开更多
Background Growing evidence links alternation of the thyroid function to the pathogenesis and progression of Alzheimer disease （AD）. However, only a few studies evaluate the association between thyroid hormone level...Background Growing evidence links alternation of the thyroid function to the pathogenesis and progression of Alzheimer disease （AD）. However, only a few studies evaluate the association between thyroid hormone levels and neuropsychiatric manifestations in patients with AD. This study aimed to investigate the relationship of thyroid hormone levels and neuropsychiatric symptoms in euthyroid patients with AD. Methods Forty patients with AD （26 women and 14 men）, with no prior AD treatment within 4 weeks before study entry, were evaluated on their thyroid status （total triiodothyronine （TT3）,total thyroxine （TT4）, and thyroid-stimulating hormone （TSH）, cognition （Mini-Mental State Examination （MMSE） and Alzheimer＇s disease Assessment Scale-Cognitive Subscale （ADAS-cog）, neuropsychiatric symptoms （Neuropsychiatric Inventory （NPI） and depression （Hamilton Rating Scale for Depression （HAMD17）. The unique relationship between thyroid hormones and cognitive function and mood was examined with multivariate linear regression analyses. The thyroid status between the neuropsychiatric symptoms group and the non-neuropsychiatric symptoms group was examined with independent-samples t-test. Results In euthyroid AD patients with agitation and irritability has lower TSH serum level than those without these symptoms （t=-2.130, P 〈0.05; t=-2.657, P 〈0.05）; and core score of HAMD is significantly associated with the serum level of TSH （β=0.395, P 〈0.01）. There is no significant association between thyroid hormone levels and cognition （MMSE, ADAS-cog and its subscale score）.展开更多
基金supported by the Science and Technology Development Project of Colleges and Universities of Tianjin Municipality, China (20110116)
文摘Hydroxysafflor yellow A （HSYA） has angiogenesis- regulating and neuro-protective effects, but its effects on vascular dementia （VaD） are unknown. In this study, 30 adult Sprague-Dawley rats were. randomly allocated to five groups： normal, sham-operation, VaD alone （bilateral carotid artery occlusion）, VaD plus saline （control）, and VaD plus HSYA. One week after operation, the HSYA group received one daily tail-vein injection of 0.6 mg/100 g HSYA for two weeks. Five weeks after operation, the spatial memory of all five groups was evaluated by the water maze task, and synaptic plasticity in the hippocampus was assessed by the long-term potentiation （LTP） method. Vascular endothelial growth factor （VEGF） and N-methyi-D- aspartic acid receptor 1 （NR1） expression in the hippocampus was detected via Western blot. We found that, compared with the group with VaD alone, the group with HSYA had a reduced escape latency in the water maze （P 〈0.05）, and the LTP at CA3- CA1 synapses in the hippocampus was enhanced （P 〈0.05）. Western blot in the late-phase VaD group showed slight up-regulation of VEGF and down- regulation of NR1 in the hippocampus, while HSYA significantly up-regulated both VEGF and NRI. These results suggested that HSYA promotes angiogenesis and increases synaptic plasticity, thus improving spatial learning and memory in the rat model of VaD.
基金supported by the National Natural Science Foundation of China,No.81671221(to RCJ)
文摘The rat high-impact free weight drop model mimics the diffuse axonal injury caused by severe traumatic brain injury in humans,while severe controlled cortical impact can produce a severe traumatic brain injury model using precise strike parameters.In this study,we compare the pathological mechanisms and pathological changes between two rat severe brain injury models to identify the similarities and differences.The severe controlled cortical impact model was produced by an electronic controlled cortical impact device,while the severe free weight drop model was produced by dropping a 500 g free weight from a height of 1.8 m through a plastic tube.Body temperature and mortality were recorded,and neurological deficits were assessed with the modified neurological severity score.Brain edema and bloodbrain barrier damage were evaluated by assessing brain water content and Evans blue extravasation.In addition,a cytokine array kit was used to detect inflammatory cytokines.Neuronal apoptosis in the brain and brainstem was quantified by immunofluorescence staining.Both the severe controlled cortical impact and severe free weight drop models exhibited significant neurological impairments and body temperature fluctuations.More severe motor dysfunction was observed in the severe controlled cortical impact model,while more severe cognitive dysfunction was observed in the severe free weight drop model.Brain edema,inflammatory cytokine changes and cortical neuronal apoptosis were more substantial and blood-brain barrier damage was more focal in the severe controlled cortical impact group compared with the severe free weight drop group.The severe free weight drop model presented with more significant apoptosis in the brainstem and diffused blood-brain barrier damage,with higher mortality and lower repeatability compared with the severe controlled cortical impact group.Severe brainstem damage was not found in the severe controlled cortical impact model.These results indicate that the severe controlled cortical impact model is relatively more stable,more reproducible,and shows obvious cerebral pathological changes at an earlier stage.Therefore,the severe controlled cortical impact model is likely more suitable for studies on severe focal traumatic brain injury,while the severe free weight drop model may be more apt for studies on diffuse axonal injury.All experimental procedures were approved by the Ethics Committee of Animal Experiments of Tianjin Medical University,China(approval No.IRB2012-028-02)in Febru ary 2012.
基金supported by the National Natural Science Foundation of China,No.30772229(to JNZ),No.81200907(to HJW)the Natural Science Foundation of Tianjin of China,No.12JCQNJC06800(to HJW)+1 种基金the Science and Technology Projects in Key Areas of Traditional Chinese Medicine of Tianjin of China,No.2018001(to ZGW)the Scientific Research Program Project of Tianjin Education Commission of China,No.2018ZD03(to ZGW)
文摘Hyperglycemia reduces the number of circulating endothelial progenitor cells, accelerates their senescence and impairs their function.However, the relationship between blood glucose levels and endothelial progenitor cells in peripheral blood of patients with traumatic brain injury is unclear. In this study, 101 traumatic brain injury patients admitted to the Department of Neurosurgery, Tianjin Medical University General Hospital or the Department of Neurosurgery, Tianjin Huanhu Hospital, China, were enrolled from April 2005 to March 2007. The number of circulating endothelial progenitor cells and blood glucose levels were measured at 1, 4, 7, 14 and 21 days after traumatic brain injury by flow cytometry and automatic biochemical analysis, respectively. The number of circulating endothelial progenitor cells and blood sugar levels in 37 healthy control subjects were also examined. Compared with controls, the number of circulating endothelial progenitor cells in traumatic brain injury patients was decreased at 1 day after injury, and then increased at 4 days after injury,and reached a peak at 7 days after injury. Compared with controls, blood glucose levels in traumatic brain injury patients peaked at 1 day and then decreased until 7 days and then remained stable. At 1, 4, and 7 days after injury, the number of circulating endothelial progenitor cells was negatively correlated with blood sugar levels(r =-0.147, P < 0.05). Our results verify that hyperglycemia in patients with traumatic brain injury is associated with decreased numbers of circulating endothelial progenitor cells. This study was approved by the Ethical Committee of Tianjin Medical University General Hospital, China(approval No. 200501) in January 2015.
基金supported by the National Natural Science Foundation of China,No.81330029(to JNZ),81501057(to YT)the Science&Technology Development Fund of Tianjin Education Commission for Higher Education in China,No.2016YD02(to YW)the Technology Program Fund of Tianjin Health and Family Planning Commission for the Key Field of Traditional Chinese Medicine,No.2018001(to ZGW)
文摘Traumatic brain injury（TBI） can result in poor functional outcomes and death, and overall outcomes are varied. Growth factors, such as angiopoietin-1（Ang-1）, vascular endothelial growth factor（VEGF）, and granulocyte-colony stimulating factor（G-CSF）, play important roles in the neurological functions. This study investigated the relationship between serum growth factor levels and long-term outcomes after TBI. Blood samples from 55 patients were collected at 1, 3 and 7 days after TBI. Blood samples from 39 healthy controls were collected as a control group. Serum Ang-1, G-CSF, and VEGF levels were measured using ELISA. Patients were monitored for 3 months using the Glasgow Outcome Scale-Extended（GOSE）. Patients having a GOSE score of 〉 5 at 3 months were categorized as a good outcome, and patients with a GOSE score of 1-5 were categorized as a bad outcome. Our data demonstrated that TBI patients showed significantly increased growth factor levels within 7 days compared with healthy controls. Serum levels of Ang-1 at 1 and 7 days and G-CSF levels at 7 days were significantly higher in patients with good outcomes than in patients with poor outcomes. VEGF levels at 7 days were remarkably higher in patients with poor outcomes than in patients with good outcomes. Receiver operating characteristic analysis showed that the best cut-off points of serum growth factor levels at 7 days to predict functional outcome were 1,333 pg/mL for VEGF, 447.2 pg/mL for G-CSF, and 90.6 ng/mL for Ang-1. These data suggest that patients with elevated levels of serum Ang-1, G-CSF, and decreased VEGF levels had a better prognosis in the acute phase of TBI（within 7 days）. This study was registered with the Chinese Clinical Trial Registry（registration number： ChiCTR1800018251） on September 7, 2018.
基金supported by a grant from the Incubation Project of Natural Science Foundation of Tianjin Medical University General Hospital in China,No.303071901401the Natural Science Foundation of Tianjin of China,No.13JCZDJC30800the National Natural Science Foundation of China,No.81271361 and 81330029
文摘A moderate stress such as cold water swimming can raise the tolerance of the body to potentially injurious events. However, little is known about the mechanism of beneficial effects induced by moderate stress. In this study, we used a classic rat model of traumatic brain injury to test the hypothesis that cold water swimming preconditioning improved the recovery of cognitive functions and explored the mechanisms. Results showed that after traumatic brain injury, pre-conditioned rats（cold water swimming for 3 minutes at 4℃） spent a significantly higher percent of times in the goal quadrant of cold water swim, and escape latencies were shorter than for non-pretreated rats. The number of circulating endothelial progenitor cells was significantly higher in pre-conditioned rats than those without pretreatment at 0, 3, 6 and 24 hours after traumatic brain injury. Immunohistochemical staining and Von Willebrand factor staining demonstrated that the number of CD34~＋ stem cells and new blood vessels in the injured hippocampus tissue increased significantly in pre-conditioned rats. These data suggest that pretreatment with cold water swimming could promote the proliferation of endothelial progenitor cells and angiogenesis in the peripheral blood and hippocampus. It also ameliorated cognitive deficits caused by experimental traumatic brain injury.
基金supported by the National Natural Science Foundation of China,No.81671902(to XC)81501704(to YC)+3 种基金the Project of Tianjin Applied Basic and Cutting-edge Technological Research of China,No.17JCYBJC25200(to XC)15JCQNJC44900(to YC)Tianjin Health Care Elite Prominent Young Doctor Development Program(to XC)the Young and Middle-aged Backbone Innovative Talent Program(to XC)
文摘Hypothalamic-pituitary-adrenal axis dysfunction may lead to the occurrence of critical illness-related corticosteroid insufficiency.Critical illness-related corticosteroid insufficiency can easily occur after traumatic brain injury,but few studies have examined this occurrence.A multicenter,prospective,cohort study was performed to evaluate the function of the hypothalamic-pituitary-adrenal axis and the incidence of critical illness-related corticosteroid insufficiency during the sub-acute phase of traumatic brain injury.One hundred and forty patients with acute traumatic brain injury were enrolled from the neurosurgical departments of three tertiary-level hospitals in China,and the critical illness-related corticosteroid insufficiency incidence,critical-illness-related corticosteroid insufficiency-related risk factors,complications,and 28-day mortality among these patients was recorded.Critical illness-related corticosteroid insufficiency was diagnosed in patients with plasma total cortisol levels less than 10μg/dL(275.9 nM)on post-injury day 4 or when serum cortisol was insufficiently suppressed(less than 50%)during a dexamethasone suppression test on post-injury day 5.The results demonstrated that critical illness-related corticosteroid insufficiency occurred during the sub-acute phase of traumatic brain injury in 5.6%of patients with mild injury,22.5%of patients with moderate injury,and 52.2%of patients with severe injury.Traumatic brain injury-induced critical illness-related corticosteroid insufficiency was strongly correlated to injury severity during the sub-acute stage of traumatic brain injury.Traumatic brain injury patients with critical illness-related corticosteroid insufficiency frequently presented with hemorrhagic cerebral contusions,diffuse axonal injury,brain herniation,and hypotension.Differences in the incidence of hospital-acquired pneumonia,gastrointestinal bleeding,and 28-day mortality were observed between patients with and without critical illness-related corticosteroid insufficiency during the sub-acute phase of traumatic brain injury.Hypotension,brain-injury severity,and the types of traumatic brain injury were independent risk factors for traumatic brain injury-induced critical illness-related corticosteroid insufficiency.These findings indicate that critical illness-related corticosteroid insufficiency is common during the sub-acute phase of traumatic brain injury and is strongly associated with poor prognosis.The dexamethasone suppression test is a practical assay for the evaluation of hypothalamic-pituitary-adrenal axis function and for the diagnosis of critical illness-related corticosteroid insufficiency in patients with traumatic brain injury,especially those with hypotension,hemorrhagic cerebral contusions,diffuse axonal injury,and brain herniation.Sub-acute infection of acute traumatic brain injury may be an important factor associated with the occurrence and development of critical illness-related corticosteroid insufficiency.This study protocol was approved by the Ethics Committee of General Hospital of Tianjin Medical University,China in December 2011(approval No.201189).
基金supported by the National Natural Science Foundation of China,No.81330029,81501057the Natural Science Foundation of Tianjin of China,No.17JCQNJC12000the Tianjin Medical University General Hospital Funding in China,No.ZYYFY2016014
文摘Traumatic brain injury can cause loss of neuronal tissue, remote symptomatic epilepsy, and cognitive deficits. However, the mechanisms underlying the effects of traumatic brain injury are not yet clear. Hippocampal excitability is strongly correlated with cognitive dysfunction and remote symptomatic epilepsy. In this study, we examined the relationship between traumatic brain injury-induced neuronal loss and subsequent hippocampal regional excitability. We used hydraulic percussion to generate a rat model of traumatic brain injury. At 7 days after injury, the mean modified neurological severity score was 9.5, suggesting that the neurological function of the rats was remarkably impaired. Electrophysiology and immunocytochemical staining revealed increases in the slope of excitatory postsynaptic potentials and long-term depression（indicating weakened long-term inhibition）, and the numbers of cholecystokinin and parvalbumin immunoreactive cells were clearly reduced in the rat hippocampal dentate gyrus. These results indicate that interneuronal loss and changes in excitability occurred in the hippocampal dentate gyrus. Thus, traumatic brain injury-induced loss of interneurons appears to be associated with reduced long-term depression in the hippocampal dentate gyrus.
基金supported by a grant from the International S cience and Technology Cooperation Projects of China,No.2011DFG33430
文摘Fluid percussion-induced traumatic brain injury models have been widely used in experimental research for years. In an experiment, the stability of impaction is inevitably affected by factors such as the appearance of liquid spikes. Management of impact pressure is a crucial factor that determines the stability of these models, and direction of impact control is another basic element. To improve experimental stability, we calculated a pressure curve by generating repeated impacts using a fluid percussion device at different pendulum angles. A stereotactic frame was used to control the direction of impact. We produced stable and reproducible models, including mild, moderate, and severe traumatic brain injury, using the MODEL01-B device at pendulum angles of 6°, 11° and 13°, with corresponding impact force values of 1.0 ± 0.11 atm（101.32 ± 11.16 k Pa）, 2.6 ± 0.16 atm（263.44 ± 16.21 k Pa）, and 3.6 ± 0.16 atm（364.77 ± 16.21 k Pa）, respectively. Behavioral tests, hematoxylin-eosin staining, and magnetic resonance imaging revealed that models for different degrees of injury were consistent with the clinical properties of mild, moderate, and severe craniocerebral injuries. Using this method, we established fluid percussion models for different degrees of injury and stabilized pathological features based on precise power and direction control.
基金supported by the National Natural Science Foundation of China(30770827,31170864and81100887)National Basic Research Development Program of China(973Program,2010CB529405)+5 种基金Key Laboratory Project of Tianjin Municipality for Science and Technology(10SYSYJC28800)Major Program of Research on Applied Fundamentals and Frontier Technologies(10JCZDJC19400)Key Program of Higher Education of Tianjin Municipality for Science and Technology(2004ZD06,20060202)Program for New Century Excellent Talents in University of China(NCET-11-1067)Key Project of Natural Science Foundation of Tianjin Municipality,China(12JCZDJC24200)Key Project for Science and Technology of Ministry of Education,China(212005)
文摘The matrix-degrading metalloproteinases （MMPs）, particularly MMP-9, play important roles in the pathogenesis and development of malignant gliomas. In the present study, the oncogenic role of MMP-9 in malignant glioma cells was investigated via antisense RNA blockade in vitro and in vivo. TJ905 malignant glioma cells were transfected with pcDNA3.0 vector expressing antisense MMP-9 RNA （pcDNA-AS-MMP9）, which significantly decreased MMP-9 expression, and cell proliferation was assessed. For in vivo studies, U251 cells, a human malignant glioma cell line, were implanted subcutaneously into 4-to 6-week-old BALB/c nude mice. The mice bearing well-established U251 gliomas were treated with intratumoral pcDNA-AS-MMP9-Lipofectamine complex （AS-MMP-9-treated group）, subcutaneous injection of endostatin （endostatin-treated group）, or both （combined therapy group）. Mice treated with pcDNA （empty vector）-Lipofectamine served as the control group. Four or eight weeks later, the volume and weight of tumor, MMP-9 expression, microvessel density and proliferative activity were assayed. We demonstrate that pcDNA-AS-MMP9 significantly decreased MMP-9 expression and inhibited glioma cell proliferation. Volume and weight of tumor, MMP-9 expression, microvessel density and proliferative activity in the antisense-MMP-9-treated and therapeutic alliance groups were significantly lower than those in the control group. The results suggest that MMP-9 not only promotes malignant glioma cell invasiveness, but also affects tumor cell proliferation. Blocking the expression of MMP-9 with antisense RNA substantially suppresses the malignant phenotype of glioma cells, and thus can be used as an effective therapeutic strategy for malignant gliomas.
基金supported by the National Natural Science Foundation of China,No.82271399(to XC)the Project of Tianjin Applied Basic and Multiple Support Research,No.21JCZDJC00910(to XC)+4 种基金the Scientific Research Program of Tianjin Education Commission(Natural Science)of China,No.2019ZD034(to QD)the Science&Technology Program of Tianjin for Cultivation of Innovative Talents,No.22JRRCRC00020(to QD)the Tianjin Medical University"Clinical Talent Training 123 Climbing Plan"(to XC)the Tianjin Health Care Elite Prominent Young Doctor Development Program(to XC)the Young and Middle-aged Backbone Innovative Talent Program(to XC)。
文摘Neutrophil extracellular traps are primarily composed of DNA and histones and are released by neutrophils to promote inflammation and thrombosis when stimulated by various inflammato ry reactions.Neutrophil extracellular trap formation occurs through lytic and non-lytic pathways that can be further classified by formation mechanisms.Histones,von Willebrand factor,fibrin,and many other factors participate in the interplay between inflammation and thrombosis.Neuroimmunothrombosis summarizes the intricate interplay between inflammation and thrombosis during neural development and the pathogenesis of neurological diseases,providing cutting-edge insights into post-neurotrauma thrombotic events.The blood-brain barrier defends the brain and spinal cord against external assaults,and neutrophil extracellular trap involvement in blood-brain barrier disruption and immunothrombosis contributes substantially to secondary injuries in neurological diseases.Further research is needed to understand how neutrophil extracellular traps promote blood-brain barrier disruption and immunothrombosis,but recent studies have demonstrated that neutrophil extracellular traps play a crucial role in immunothrombosis,and identified modulators of neuro-immunothrombosis.However,these neurological diseases occur in blood vessels,and the mechanisms are unclear by which neutrophil extracellular traps penetrate the blood-brain barrier to participate in immunothrombosis in traumatic brain injury.This review discusses the role of neutrophil extracellular traps in neuro-immunothrombosis and explores potential therapeutic interventions to modulate neutrophil extracellular traps that may reduce immunothrombosis and improve traumatic brain injury outcomes.
基金the National Natural Science Foundation of China,No. 30973090the Natural Science Foundation of Tianjin,No.09JCZDJC17200
文摘BACKGROUND：Endogenous neural progenitor cells play a beneficial role for cognitive recovery following traumatic brain injury.However,there are few classification-control studies aimed at varying graded brain trauma.OBJECTIVE：To observe the effects of adult endogenous neurogenesis on cognitive function repair and regeneration of neural progenitor cells following varying graded traumatic hippocampal injury to determine the significance of endogenous neurogenesis in the repair of brain injury.DESIGN,TIME AND SETTING：A randomized,controlled,animal experiment was performed at the Key Laboratory of Injuries,Variations and Regeneration of Nervous System,Tianjin Medical University General Hospital,from February to October 2009.MATERIALS：Mouse anti-rat 5-bromodeoxyuridine （BrdU） and neuronal nuclei （NeuN） monoclonal antibodies were purchased from Millipore Corporation,USA.METHODS：A total of 45 Wistar rats were randomly assigned to three groups.Mild and severe injury groups were respectively subjected to （182 ± 2） kPa and （284 ± 4） kPa lateral fluid percussion to establish models of brain injury,and the control group was subjected to surgery with no lateral fluid percussion.MAIN OUTCOME MEASURES：Cognitive function was estimated using the Morris water maze.Proliferation,survival,and differentiation of newly generated cells in the injured hippocampus were observed through the use of immunofluorescent staining.RESULTS：At 7 days post-injury,the number of BrdU＋ cells in the hippocampal dentate gyrus significantly increased in the mild and severe injury groups compared with the control group （P〈0.01）.At 61 days post-injury,the number of BrdU7NeuN＋ cells in the hippocampal dentate gyrus was significantly greater in the mild injury group compared with the severe injury and control groups （P〈 0.01）.In addition,the control group exhibited the greatest proportion of surviving cells that differentiated into mature neurons compared with the injury groups （P〈 0.01）.Moreover,at 61 days post-injury,cognitive function in rats with mild injury recovered to normal levels,whereas the severe injury group exhibited cognitive deficits （P〈 0.01）.CONCLUSION：Traumatic brain injury may be a stimulation factor for proliferation of neural progenitor cells in the adult hippocampus but severe brain trauma does not lead to an increased number of newly generated cells.Endogenous adult neurogenesis repairs neurological functions to an extent.However,recovery of neurological function remains limited following severe traumatic brain injury.
基金This work was supported by grants from the National Natural Science Foundation of China （No. 81000533）, the Project of Tianjin Applied Basic and Cutting-edge Technological Research （No. 13JCQNJC10500） and National Key Basic Research Program in China （No. 2005CB522600）. Conflicts of interest： none.
文摘Background Traumatic brain injury （TBI） is a heterogeneous condition that can lead to critical LLLness-related corticosteroid insufficiency （CIRCI） causing a high mortality and morbidity.Glucocorticoids were widely used in the clinical management of TBI,but their benefit has been challenged in some studies and their efficacy,especially for treating CIRCI in TBI patients,remains unclear.Methods We conducted a meta-analysis of published data to determine if the controversy is related to clinical dosing and timing of glucocorticoids （GCs） application.We analyzed published reports in four databases （MEDLINE,EMBASE,the Cochrane Controlled Trials Register,and CBMdisc）.The published data were stratified into not only low-and high-dose GCs group but also short-and long-term GCs group to compare their effectiveness in improving TBI outcomes.Results We totally identified 16 reports.For low-dose patients,the pooled relative risks （RRs） for two clinical outcomes of death or a combination of death and severe disability were 0.95 （95% confidence interval （CI）：0.80 to 1.13） and 0.95 （95% CI：0.83 to 1.09）,respectively.The risks for infection and gastrointestinal bleeding were 0.85 （95% CI：0.50 to 1.45） and 0.64 （95% Cl：0.15 to 2.70）,respectively.For high-dose group,the pooled RR of death is 1.14 （95% Cl：1.06 to 1.21）.The pooled RRs for infection and gastrointestinal bleeding for the high-dose patients were 1.04 （95% CI：0.93 to 1.15） and 1.26 （95% CI：0.92 to 1.75）,respectively.For long-term use group,the pooled RRs for two clinical outcomes of death or a combination of death and severe disability were 0.98 （95% CI：0.87 to 1.12） and 1.00 （95% CI：0.90 to 1.11）,respectively.The risks for infection and gastrointestinal bleeding were 0.88 （95% CI：0.71 to 1.11） and 0.96 （95% CI：0.35 to 2.66）,respectively.For short-term use group,the pooled RR of death is 1.15 （95% CI：1.07 to 1.23）,and importantly the effects on infections were beneficial in terms of TBI patients suffering from CIRCI.Conclusions This meta-analysis suggests an increased risk of death for TBI patients on a high dose and short term of glucocorticoids compared with those on a low dose and long term,for whom a trend towards clinical improvement is evident.In addition,stress-does of GCs further decrease the pneumonia incidence in TBI patients suffering from CIRCI.A large-scale multicenter randomized controlled trial is warranted for testing （1） the efficacy of stress-dose GCs treatment in the sub-acute phase of TBI （4-21 days after initial trauma）,when CIRCI is most likely to occur; （2） the hypothesis that stress-dose GCs could boost patients＇ stress function and ensure survival.
基金supported by grants 81971176,81720108015,and 81971173 from the National Natural Science Foundation of China19YFZCSY00650,17JCZDJC35900,15ZXLCSY00060,and 15ZXJZSY00040 from the Tianjin Research Program of Advanced Technology.
文摘Chronic subdural hematoma(CSDH)is a chronic space-occupying lesion formed by blood accumulation between arachnoid and dura mater,which is usually formed in the third week after traumatic brain injury.Surgical treatment is usually the first choice for patients with CSDH having a significant space-occupying effect.Most of the patients showed good results of surgical treatment,but still some patients had a postoperative recurrence(the recurrence rate was up to 33%).Because CSDH is often seen in the elderly,patients are weak and have many basic diseases.The risk of surgical treatment is high;serious complications and even death(the death rate is up to 32%)can often occur.The overall good prognosis rate of patients aged more than 90 years is 24%.The drug treatment can provide a safe and effective treatment for elderly patients who are weak,intolerable to surgery,or failed in surgery.Low-dose and long-term use of atorvastatin(20mg/d)is suggested for continuous treatment for at least 8 weeks,while low-dose and short-term use of dexamethasone can improve the therapeutic effect of atorvastatin on CSDH.Patients should undergo CT or MRI scanning at least one time within 2 weeks after the start of drug treatment.
基金supported by grants from the National Natural Science Foundation of China(No.81671902)the Project of Tianjin Applied Basic and Cutting-edge Technological Research(No.17JCYBJC25200)by the Tianjin Health Care Elite Prominent Young Doctor Development Program and Young,and middle-aged innovative talent training program.
文摘Background::Extra-corporeal video telescope operating monitor system provides a necessary instrument to perform high-precision neurosurgical procedures that could substitute or supplement the traditional surgical microscope.The present study was designed to evaluate a compact high-definition two-dimensional exoscope system for assisting in surgical removal of large vestibular schwannoma(VS),as an alternative to a binocular surgical microscope.Methods::Patients with Koos grade 3 and grade 4 VS undergoing surgery were enrolled in this prospective cohort study between January 2013 and June 2018.The demographics and tumor characteristics(size,Koos grade,composition[cystic or solid mass])were matched between the two groups of patients.The following outcome measurements were compared between the two groups:duration of surgery,volume of blood loss,extent of tumor resection,number of operating field adjustments,pre-and post-operative facial and cochlear nerve function evaluated at 3 months post-surgery,complications and surgeons’comfortability.Results::A total of 81 patients received tumor resection through the retrosigmoid approach under either an exoscope(cases,n=39)or a surgical microscope(control,n=42).Patients in the two groups had comparable tumor location(P=0.439),Koos grading(P=0.867),and composition(P=0.891).While no significant differences in the duration of surgery(P=0.172),extent of tumor resection(P=0.858),facial function(P=0.838),and hearing ability(P=1.000),patients operated on under an exoscope had less blood loss(P=0.036)and a fewer field adjustments(P<0.001).Both primary and assistant surgeons reported a high level of comfort operating under the exoscope(P=0.001 and P<0.001,respectively).Conclusions::The compact high-definition two-dimensional exoscope system provides a safe and efficient means to assist in removing large VSs,as compared to a surgical microscope.After the acquaintance with a visual perception through a dynamic hint and stereoscopically viewing corresponding to the motion parallax,the exoscope system provided a comfortable,high-resolution visualization without compromising operational efficiency and patient safety.
基金supported by the National Key Research and Development Program of China(No.2019YFA0903801)the National Natural Science Foundation of China(Nos.52073015,51773151,52003021,and 81671169)+2 种基金Tianjin Municipal Health Bureau(No.2010KY11)Postdoctoral Science Foundation of China(No.2015M580212)Fundamental Research Funds for the Central Universities(No.ZY2006).
文摘Brain ischemia is the second leading cause of death and the third leading cause of disability in the world.Systemic delivery of microRNA,a class of molecules that regulate the expression of cellular proteins associated with angiogenesis,cell growth,proliferation and differentiation,holds great promise for the treatment of brain ischemia.However,their therapeutic efficacy has been hampered by poor delivery efficiency of microRNA.We report herein a platform technology based on microRNA nanocapsules,which enables their effective delivery to the disease sites in the brain.Exemplified by microRNA-21,intravenous injection of the nanocapsules into a rat model of cerebral ischemia could effectively ameliorate the infarct volume,neurological deficit and histopathological severity.
基金This work was supported by grants from the National ＂973 Projects＂ of China （No. 2005CB522605）, Tianjin Science and Technology Development Plan （No. 05YFGDSF02500） and Tianjin Natural Science Foundation （No. 033611511）. No competing financial interests exist.
文摘Background Traumatic brain injury （TBI） often causes cognitive deficits and remote symptomatic epilepsy. Hippocampal regional excitability is associated with the cognitive function. However, little is known about injury-induced neuronal loss and subsequent alterations of hippocampal regional excitability. The present study was designed to determine whether TBI may impair the cellular circuit in the hippocampus.Methods Forty male Wistar rats were randomized into control （n=-20） and TBI groups （n=20）. Long-term potentiation, extracellular input/output curves, and hippocampal parvalbumin-immunoreactive and cholecystokinin-immunoreactive interneurons were compared between the two groups.Results TBI resulted in a significantly increased excitability in the dentate gyrus （DG）, but a significantly decreased excitability in the cornu ammonis 1 （CA1） area. Using design-based stereological injury procedures, we induced interneuronal loss in the DG and CA3 subregions in the hippocampus, but not in the CA1 area. Conclusions TBl leads to the impairment of hippocampus synaptic plasticity due to the changing of interneuronal interaction. The injury-induced disruption of synaptic efficacy within the hippocampal circuit may underlie the observed cognitive deficits and symptomatic epilepsy.
文摘Background Endothelial dysfunction is thought to be critical events in the pathogenesis of Alzheimer＇s disease （AD）.Endothelial progenitor cells （EPCs） have provided insight into maintaining and repairing endothelial function. To study the relation between EPCs and AD, we explored the number of circulating EPCs in patients with AD.Methods A total of 104 patients were recruited from both the outpatients and inpatients of the geriatric neurology department at General Hospital, rianjin Medical University. Consecutive patients with newly diagnosed AD （n=30）,patients with vascular dementia （VaD, n=34）, and healthy elderly control subjects with normal cognition （n=40） were enrolled after matching for age, gender, body mass index, medical history, current medication and Mini Mental State Examination. Middle cerebral artery flow velocity was examined with transcranial Doppler. Endothelial function was evaluated according to the level of EPCs, and peripheral blood EPCs was counted by flow cytometry.Results There were no significant statistical differences of clinical data in AD, VaD and control groups （P 〉0.05）. The patients with AD showed decreased CD34-positive （CD34＋） or CD133-positive （CD133＋） levels compared to the control subjects, but there were no significant statistical differences in patients with AD. The patients with AD had significantly lower CD34＋CD133＋ EPCs（CD34 and CD133 double positive endothelial progenitor cells） than the control subjects （P 〈0.05）. In the patients with AD, a lower CD34＋CD133＋ EPCs count was independently associated with a lower Mini-Mental State Examination score （r=0.514, P=0.004）. Patients with VaD also showed a significant decrease in CD34＋CD133＋ EPCs levels, but this was not evidently associated with the Mini-Mental State Examination score. The changes of middle cerebral artery flow velocity were similar between AD and VaD. Middle cerebral artery flow velocity was decreased in the AD and VaD groups and significantly lower than the normal control group （P 〈0.01）. There was no significant difference of the blood flow velocity between the AD and VaD patients （P 〉0.05）.Conclusions The results provided evidence that patients with AD have reduced circulating EPCs. Endothelial function is impaired in patients with AD and vascular factors have a role in the pathogenesis of AD. CD34＋CD133＋ EPCs may be a novel biomarker of AD dementia.
基金This work was partially supported by grants from the National Natural Science Foundation of China （No. 30772229） and the Research Fund for the Doctoral Program of Higher Education in China （No. 20070062008）.
文摘Traumatic brain injury （TBI） is a major cause of mortality and morbidity in the world. Recent clinical investigations and basic researches suggest that strategies to improve angiogenesis following TBI may provide promising opportunities to improve clinical outcomes and brain functional recovery. More and more evidences show that circulating endothelial progenitor cells （EPCs）, which have been identified in the peripheral blood, may play an important role in the pathologic and physiological anglo-genesis in adults. Moreover, impressive data demonstrate that EPCs are mobilized from bone marrow to blood circula- tion in response to traumatic or inflammatory stimulations. In this review, we discussed the role of EPCs in the repair of brain injury and the possible therapeutic implication for func- tional recovery of TBI in the future.
文摘Background Growing evidence links alternation of the thyroid function to the pathogenesis and progression of Alzheimer disease （AD）. However, only a few studies evaluate the association between thyroid hormone levels and neuropsychiatric manifestations in patients with AD. This study aimed to investigate the relationship of thyroid hormone levels and neuropsychiatric symptoms in euthyroid patients with AD. Methods Forty patients with AD （26 women and 14 men）, with no prior AD treatment within 4 weeks before study entry, were evaluated on their thyroid status （total triiodothyronine （TT3）,total thyroxine （TT4）, and thyroid-stimulating hormone （TSH）, cognition （Mini-Mental State Examination （MMSE） and Alzheimer＇s disease Assessment Scale-Cognitive Subscale （ADAS-cog）, neuropsychiatric symptoms （Neuropsychiatric Inventory （NPI） and depression （Hamilton Rating Scale for Depression （HAMD17）. The unique relationship between thyroid hormones and cognitive function and mood was examined with multivariate linear regression analyses. The thyroid status between the neuropsychiatric symptoms group and the non-neuropsychiatric symptoms group was examined with independent-samples t-test. Results In euthyroid AD patients with agitation and irritability has lower TSH serum level than those without these symptoms （t=-2.130, P 〈0.05; t=-2.657, P 〈0.05）; and core score of HAMD is significantly associated with the serum level of TSH （β=0.395, P 〈0.01）. There is no significant association between thyroid hormone levels and cognition （MMSE, ADAS-cog and its subscale score）.
