Survivin在创伤性脑损伤中的研究进展

创伤性脑损伤是高致残率和致死率的疾病,是目前全世界共同关注的公共卫生和社会经济学问题。每年美国创伤性脑损伤导致的经济负担估计超过600亿美元,全球创伤性脑损伤的发病率均在增加,尤其是在发展中国家。

脑室-腹腔分流术治疗创伤性脑积水的效果分析

创伤性脑致伤具有较高的病死率和致残率,而救治成功的患者也易发生脑部并发症,脑积水是常见的并发症之一,其发病机制较为复杂,与颅内环境密切相关。目前,脑积水的治疗主要采取分流手术,脑室-腹腔分流术可在腹腔镜协助下快速完成,具有创伤小、操作简单、分流效果好等优点[1]。本研究回顾性分析了创伤性脑致伤发生脑积水患者的临床资料,探讨其影响因素并评价脑室-腹腔分流术的临床疗效。

Effects of intestinal mucosal blood flow and motility on intestinal mucosa

AIM： To investigate the role of intestinal mucosal blood flow （IMBF） and motility in the damage of intestinal mucosal barrier in rats with traumatic brain injury. METHODS： Sixty-four healthy male Wistar rats were divided randomly into two groups： traumatic brain injury （TBI） group （n = 32）, rats with traumatic brain injury; and control group （n = 32）, rats with sham-operation. Each group was divided into four subgroups （n = 8） as 6, 12, 24 and 48 h after operation. Intestinal motility was measured by the propulsion ratio of a semi-solid colored marker （carbon-ink）. IMBF was measured with the laser-Doppler technique. Endotoxin and D-xylose levels in plasma were measured to evaluate the change of intestinal mucosal barrier function following TBI. RESULTS： The level of endotoxin was significantly higher in TBI group than in the control group at each time point （0.382 ± 0.014 EU/mL vs 0.102 ± 0.007 EU/mL, 0.466 ± 0.018 EU/mL vs 0.114 ± 0.021 EU/mL, 0.478± 0.029 EU/mL vs 0.112 ±- 0.018 EU/mL and 0.412± 0.036 EU/mL vs 0.108 ±0.011 EU/mL, P 〈 0.05）. D-xylose concentrations in plasma in TBI group were significantly higher than in the control group （6.68 ± 2.37 mmol/L vs 3.66 ±1.07 retool/L, 8.51 ± 2.69 mmol/L vs 3.15 ＋ 0.95 mmol/L, 11.68 ±3.24 mmol/L vs 3.78 ± 1.12 mmol/L and 10.23 ± 2.83 mmol/L vs 3.34 ± 1.23 mmol/L, P 〈 0.05）. The IMBF in TBI group was significantly lower than that in the control group （38.5 ± 2.8 PU vs 45.6 ± 4.6 PU, 25.2 ± 3.1 PU vs 48.2 ± 5.3 PU, 21.5 ± 2.7 PU vs 44.9 ± 2.8 PU, 29. 4 ± 3.8 PU vs 46.7 ± 3.2 PU） （P 〈 0.05）. Significant decelerations of intestinal propulsion ratio in T8I groups were found compared with the control group （0.48% ± 0.06% vs 0.62%± 0.03%, 0.37% ±0.05% vs 0.64% ± 0.01%, 0.39% ± 0.07% vs 0.63% =1= 0.05% and 0.46% ± 0.03% vs 0.65% ± 0.02%） （P 〈 0.05）. CONCLUSION： The intestinal mucosal permeability is increased obviously in TBI rats. Decrease of intestinal motility and IMBF occur early in TBI, both are important pathogenic factors for stress-related damage of the intestinal mucosal barrier in TBI.

Cognitive improvement following transvenous adipose-derived mesenchymal stem cell transplantation in a rat model of traumatic brain injury

The effects of adipose-derived mesenchymal stem cell (ADMSC) transplantation for the repair of traumatic brain injury remain poorly understood. The present study observed neurological functional changes in a rat model of traumatic brain injury following ADMSC transplantation via the tail vein. Cell transplants were observed in injured cerebral cortex, and expression of brain-derived nerve growth factor was significantly increased in the injured hippocampus following transplantation. Results demonstrated that transvenous ADMSC transplants migrated to the injured cerebral cortex and significantly improved cognitive function.

Risk Factors Analysis on Traumatic Brain Injury Prognosis

Objective To investigate the independent risk factors of traumatic brain injury （TBI） prognosis. Methods A retrospective analysis was performed in 885 hospitalized TBI patients from January 1, 2003 to January 1, 2010 in the First Affiliated Hospital of Medical College of Xi＇an Jiaotong LIniversity. Sin- gle-factor and logistic regression analysis were conducted to evaluate the association of different variables with TBI outcome. Results The single-factor analysis revealed outcome, including age （P=0.044 for the age group （P〈0.O01）, cerebrospinal fluid leakage （P〈0.001）, reflex （P〈0.001）, shock （P〈0.001）, associated （P〈0.001）, cerebral contusion （P〈0.001）, diffuse significant association between several variables and TB1 40-60, P〈0.00l for the age group ≥60）, complications Glasgow Coma Scale （GCS） （P〈0.001）, pupillary light extra-cranial lesions （P=0.01）, subdural hematoma axonal injury （P〈0.001）, and subarachnoid hemorrhage （P〈0.001）, suggesting the influence of those factors on the prognosis of TBI. Furthermore, logistic regression analysis identified age, GCS score, pupillary light reflex, subdural hematoma, and subarachnoid hemorrhage as independent risk factors of TB1 prognosis. Conclusion Age, GCS score, papillary light reflex, subdural hematoma, and subarachnoid hemorrhage may be risk factors influencing the prognosis of TBI. Paying attention to those factors might improve the outcome of TBI in clinical treatment.

Concussion management in soccer

Brain injuries in sports drew more and more public attentions in recent years. Brain injuries vary by name, type, and severity in the athletic setting. It should be noted, however, that these injuries are not isolated to only the athletic arena, as non-athletic mechanisms （e.g., motor vehicle accidents） are more common causes of traumatic brain injuries （TBI） among teenagers. Notwithstanding, as many as 1.6 to 3.8 million TBI result from sports and recreation each year in the United States alone. These injuries are extremely costly to the global health care system, and make TBI among the most expensive conditions to treat in children. This article serves to define common brain injuries in sport; describe their prevalence, what happens to the brain following injury, how to recognize and manage these injuries, and what you can expect as the athlete recovers. Some return-to-activity considerations for the brain-injured athlete will also be discussed.

Postural control deficits identify lingering post-concussion neurological deficits

Concussion,or mild traumatic brain injury,incidence rates have reached epidemic levels and impaired postural control is a cardinal symptom.The purpose of this review is to provide an overview of the linear and non-linear assessments of post-concussion postural control.The current acute evaluation for concussion utilizes the subjective balance error scoring system(BESS) to assess postural control.While the sensitivity of the overall test battery is high,the sensitivity of the BESS is unacceptably low and,with repeat administration,is unable to accurately identify recovery.Sophisticated measures of postural control,utilizing traditional linear assessments,have identified impairments in postural control well beyond BESS recovery.Both assessments of quiet stance and gait have identified lingering impairments for at least 1 month post-concussion.Recently,the application of non-linear metrics to concussion recovery have begun to receive limited attention with the most commonly utilized metric being approximate entropy(Ap En).Ap En,most commonly in the medial-lateral plane,has successfully identified impaired postural control in the acute post-concussion timeframe even when linear assessments of instrumented measures are equivalent to healthy pre-injury values;unfortunately these studies have not gone beyond the acute phase of recovery.One study has identified lingering deficits in postural control,utilizing Shannon and Renyi entropy metrics,which persist at least through clinical recovery and return to participation.Finally,limited evidence from two studies suggest that individuals with a previous history of a single concussion,even months or years prior,may display altered Ap En metrics.Overall,non-linear metrics provide a fertile area for future study to further the understanding of postural control impairments acutely post-concussion and address the current challenge of sensitive identification of recovery.

Arousal effect and potential mechanism of dopamine-mediated acupuncture on traumatic brain injury

Traumatic brain injury(TBI)is a brain injury caused by direct external forces,and its prognosis depends on the extent of the damage and the changes in level of consciousness.Timely awakening from a coma is the first thorny problem to be solved in TBI treatment.Therefore,there is a need for the development of safe and effective methods for timely awakening after TBI coma.Dopamine(DA)and its receptors in the nervous system are involved in the regulation of wakefulness.The amount and activity of dopaminergic neurons can affect cellular function and neuroinflammatory response,and are also significant for the awakening process after TBI.The current common awakening therapy for TBI may also be related to the activation of dopaminergic neurons.Acupuncture plays a beneficial role in timely awakening,recovery of conscious level,and functional rehabilitation after TBI.The mechanism may be related to the targeted regulation of DA and its receptors via acupuncture.Among acupuncture first aid therapies,acupuncture at hand 12 Jing-Well points,with its advantages of simple operation and ultra-early intervention,has shown great promise in timely awakening following TBI and triggering a series of subsequent nerve repair effects in the treatment of TBI.We here present a review that provides a new perspective for the timely awakening from TBI-induced coma,with a focus on the role of DA in the regulation of wakefulness and the efficacy and potential mechanism of DA systems in the treatment of TBI by acupuncture.

NMDA receptor antagonist MK-801 reduces neuronal damage and preserves learning and memory in a rat model of traumatic brain injury

Objective NMDA receptor channel plays an important role in the pathophysiological process of traumatic brain injury （TBI）. The present study aims to study the pathological mechanism of TBI and the impairment of learning and memory after TBI, and to investigate the mechanism of the protective effect of NMDA receptor antagonist MK-801 on learning and memory disorder after TBI. Methods Forty Sprague-Dawley rats （weighing approximately 200 g） were randomized into 5 groups （n = 8 in each group）： control group, model group, low-dose group （MK-801 0.5 mg/kg）, middle-dose group （MK-801 2 mg/kg）, and high-dose group （MK-801 10 mg/kg）. TBI model was established using a weight-drop head injury mode. After 2-month drug treatment, learning and memory ability was evaluated by using Morris water maze test. Then the animals were sacrificed, and brain tissues were taken out for morphological and immunohistochemical assays. Results The ability of learning and memory was significantly impaired in the TBI model animals. Besides, the neuronal caspase-3 expression, neuronal nitric oxide synthase （nNOS）-positive neurons and OX-42-positive microglia were all increased in TBI animals. Meanwhile, the number of neuron synapses was decreased, and vacuoles degeneration could be observed in mitochondria. After MK-801 treatment at 3 different dosages, the ability of learning and memory was markedly improved, as compared to that of the TBI model animals. Moreover, neuronal caspase-3 expression, OX-42-positive microglia and nNOS-positive neurons were all significantly decreased. Meanwhile, the mitochondria degeneration was greatly inhibited. Conclusion MK-801 could significantly inhibit the degeneration and apoptosis of neurons in damaged brain areas. It could also inhibit TBI-induced increase in nNOS-positive neurons and OX-42-positive microglia. Impairment in learning and memory in TBI animals could be repaired by treatment with MK-801.

Influencing factors for posttraumatic hydrocephalus in patients suffering from severe traumatic brain injuries

Objective： To detect the influencing factors for posttraumatic hydrocephalus in patients with severe traumatic brain injuries and provide theoretical reference for clinical treatment. Methods ： Retrospective study was made on 139 patients with severe traumatic brain injuries in our hospital. The patients were divided into two groups： hydrocephalus group and non-hydrocephalus group. Single factor analysis and multiple factor analysis were used to determine the related factors and hydrocephalus. Multiple factor analysis was conducted with logistic regression. Results： Posttraumatic hydrocephalus was found in 19.42% of patients. Age （ OR=1.050, 95% CI： 1.012-1. 090 ）, decompressive craniectomy （ OR =4.312, 95 %CI ： 1. 127-16.503 ）, subarachnoid hemorrhage （ OR = 43.421, 95 % CI ： 7. 835-240. 652 ） and continuous lumbar drainage of cerebrospinal fluid （ OR =0.045, 95%CI： 0. 011-0. 175） were screened out from nine factors as the influencing factors for posttraumatic hydrocephalus. Conclusions ： Risk factors for PTH are as follows： age, deeompressive eranieetomy and subaraehnoid hemorrhage （SAH）. Continuous lumbar drainage of eerebrospinal fluid can greatly reduce posttraumatic hydrocephalus.

Complications induced by decompressive craniectomies after traumatic brain injury

Objective: To find out the optimal approach to decompress externally the severe injured brain and to avoid possible complications caused by external decompression. Methods: 68 patients who underwent external decompression after traumatic brain injury were admitted into Tianjin Medical University General Hospital for cranioplasty from 1995 to 2001. Complications were retrospectively investigated and analyzed in all patients. The findings were compared between the patients who accepted the decompressive craniectomy in our hospital and in local hospitals. χ 2-test was employed for statistical analysis and complication evaluation. Results: Large craniectomy definitely caused some side effects to patients. Among various complications, several of them showed significantly high incidence (P< 0.05) in patients who underwent the decompressive operation in local hospitals such as shunt-dependent hydrocephalous, subdural fluid collection, and CSF leakage from scalp incision. The rest of the complications had no remarkable difference (P> 0.05) between the two groups including dilation or/and migration of lateral ventricle underlying the cranial defect, skin flap concavity, encephalomalacia of the decompressive area, seizure and infection. Conclusions: To reduce the incidence of iatrogenic side effects, surgical craniectomy should be performed according to the strict indication and standard and any abuse should be avoided.

Dynamic change of serum protein S100b and its clinical significance in patients with traumatic brain injury

Objective: To analyze the dynamic change of serum protein S100b in patients with traumatic brain injury and its clinical value in assessing brain damage. Methods: According to Glasgow coma scale (GCS), 102 cases of traumatic brain injury were divided into mild brain injury group (GCS≥13, n=31, Group A), moderate brain injury group (8<GCS<13, n=37, Group B) and severe brain injury group (GCS≤8, n=34, Group C). Serial S100b concentrations were analyzed by enzyme-linked immunosorbent assay (ELISA) in blood samples taken on admission, 12 h, 24 h, 48 h, 72 h and 7 days after traumatic brain injury. Results: The severe brain injury group showed significantly higher concentration of serum S100b, with earlier increase and longer duration, than the mild and moderate brain injury groups. The patients with higher S100b exhibited lower GCS scores and poor clinical prognosis. The increase in S100b could emerge before clinical image evidence indicated so. Conclusions: Serum S100b can be used as a sensitive index for assessment and prediction of traumatic brain injury severity and prognosis.

Effect of Xingnaojing injection on cerebral edema and blood-brain barrier in rats following traumatic brain injury

Objective：To explore the effects of Xingnaojing injection on cerebral edema and blood-brain barrier （BBB） in rats following traumatic brain injury （TBI）.Methods： A total of 108 adult male Sprague-Dawley rats were used as subjects and randomly assigned to three groups：sham-operation,TBI and Xingnaojing injection was set up by the improved device of Feeney＇s weightcontent and BBB permeability expressed as Evans blue content were measured at 1, 3, 5 and 7 days after surgery.Results： In sham-operation group, brain water content and Evans blue content in brain tissue were 78.97%±1.22%and 5.13μg±0.71μg. Following TBI, water content in brain tissue was increased significantly at 1, 3, 5 and 7 days （83.49%±0.54%, 82.74%±0.72%, 80.22%±0.68%, 79.21%±0.60%）, being significantly higher than that in sham operation group （P〈0.05）. Evans blue content was increased in TBI group （16.54 μg±0.60 μg, 14.92μg±0.71μg, 12.44 μg ±0.92μg, 10.14μg±0.52 μg） as compared with sham-operation group（P〈0.05）. After treatment with Xingnaojing injection, brain water content decreased as compared with TBI group （81.91%±1.04%, 80.38%±0.72%, 79.54%±0.58%,78.60%±0.77%, P〈0.05）. Xingnaojing injection also reduced the leakage of BBB as compared with TBI group （15.11 μg± 0.63 μg, 13.62 μg±0.85μg, 10.06 μg±0.67 μg, 9.54 μg±0.41 μg,P〈0.05）.Conclusion： Xingnaojing injection could alleviate cerebral edema following TBI via reducing permeability ofBBB.

Effect of dipeptide of glutamine and alanine on severe traumatic brain injury

Objective： To determine the effect of dipeptide of glutamine and alanine on patients with severe traumatic brain injury. Methods： A total of 46 patients （31 males and 15 females, aged 7-68 years, （ 47 ± 9. 6 ） years on average ） with severe traumatic brain injury were randomized into two groups： Group G （n=23） and Group C （n =23）. The patients in Group G received nutritional remedy with the dipeptide of glutamine and alanine, whereas the patients in Group C received routine nutritional therapy only. GCS changes, the length of stay in the neurosurgical intensive care unit （NICU）, the mortality, the count of lymphocytes, related complications including lung infection and hemorrhage of alimentary tracts, etc, were examined and recorded. Results： The fatality rate and the length of stay in NICU in Group G was lower than these in Group C （P〈0.05）, but no obvious difference was found in GCS changes of the patients between the two groups （ P 〉 0.05 ）. The patients with lung infection and alimentary tract hemorrhage in Group G were less than those in Group C （P〈0.05）. The count of lymphocytes in Group G was more than that in Group C （P 〈0.05）, but no difference was found in other nutritional data. Conclusions： Dipeptide of glutamine and alanine can increase the resisting stress and anti-infection ability of patients with severe traumatic brain injury, which can also lower the mortality and shorten the NICU stay.

Evaluation of stress hormones in traumatic brain injury patients with gastrointestinal bleeding

Objective： To evaluate the local risk factors of traumatic brain injury （TBI） patients developing gastrointestinal （GI） bleeding during the early hospitalization in neurosurgery intensive care unit （NICU）. Method： From September 2005 to February 2006, 41 patients admitted to NICU and 13 healthy volunteers were involved in our study. Blood samples at 24 hours, 2-3 days and 5-7 days were obtained from each patient via arterial line at 8 a.m. to measure the concentrations of serum adrenocorticotropic hormone （ACTH）, total cortisol and gastrin. The collected serum was immersed in an ice bath and tested by the Immulite 1000 systems. Data were analyzed by SPSS 11.5. Results： Within 24 hours following TBI, the concentrations of total cortisol, ACTH and gastrin increased proportionally to the severity of injury, especially significant in the experimental group （P〈0.05）. The concentrations of ACTH and gastrin were higher in the GI bleeding positive group than in the GI bleeding negative group, （F=1.413, P=0.253） for ACTH and （F=9.371, P=0.006） for gastrin. GI bleeding had a positive correlation with gastrin concentration （r=0. 312, P〈0.05） and a negative correlation with serum hemoglobin （Hb） （r=-0.420, P〈0.01）. The clinical incidence of GI bleeding was 24.39% （10/41） in the experimental group. Within 24 hours, GI bleeding had a strong correlation with gastrin concentration （OR=26.643, P〈0.05） and hematocrit （Hct） （OR=5.385, P〈0.05）. High ACTH concentration （〉100 pg/ml） increased the frequency of GI bleeding. For patients with severe TBI and treated with routine antacids, the incidence of GI bleeding was 40.91% （9/22） and the mortality rate was 20%（2/10）. Conclusions： Low Glasgow coma scale scores, low Hb, high concentrations of gastrin and ACTH （〉 100 pg/ml） are risk factors and can be predictive values for post-traumatic GI bleeding. Severe TBI patients have high risks of GI bleeding with high mortality.

Changes of serum Tau, GFAP, TNF-α and malonaldehyde after blast-related traumatic brain injury

Objective： To determine the changes of serum Tau protein, glial fibrillary acidic protein （GFAP）, tumor necrosis factor alpha （TNF-α）, and malonaldehyde （MDA） in rats after blast-related traumatic brain injury （BTBI） and to provide relative information for further studies on BTBI mechanism and seek specific biomarkers for BTBI. Methods： Ninety male Sprague-Dawley rats were randomly assigned into three groups： control group, moderate blast injury group, and severe blast injury group （n=30 for each）. Rats in the moderate and severe blast injury groups were respectively exposed to corresponding levels of BTBI. After explosion, serum levels of Tau, GFAP, TNF-α, and MDA in each group were determined by Elisa assay at different time points after injury （8 h, 24 h, 3 d, and 6 d）. The extent of brain damage was detected by Nissl staining and TUNEL assay. Results： Serum levels of Tau and GFAP rapidly increased and reached the peak at 24 h after either moderate or severe blast injury. All the values were significantly higher than control group at all time points （P〈0.05）. Serum TNF-α level of both injury groups peaked at 8 h after BTBI and stayed significantly higher than control group at all time points （P〈0.05）. Serum MDA of two injury groups began to significantly increase at 3 d and the level stayed significantly higher than control group until 6 d （P〈0.05）. Moreover, unlike the other biomarkers, serum MDA of severe blast injury group was significantly higher than moderate blast injury group at 6 d （P〈0.05）. Conclusion： The changes of serum Tau, GFAP, and TNF-α showed a good sensitivity at the acute phase after BTBI （within 24 h）. However, their specificity and correlation with the extent of injury were limited in this experiment. Moreover, although the change of serum MDA showed a poor sensitivity and specificity to the diagnosis of BTBI during the first few days, it can reflect the injury degree at 6 d after injury. Therefore, further studies are needed to improve the methods of detecting more serum markers and investigate the significance of multiple markers in diagnosing BTBI.

Correlation of cell apoptosis with brain edema and elevated intracranial pressure in traumatic brain injury

Objective: To study the correlation between brain edema, elevated intracranial pressure (ICP) and cell apoptosis in traumatic brain injury (TBI). Methods: In this study, totally 42 rabbits in 7 groups were studied. Six of the animals were identified as a control group, and the remaining 36 animals were equally divided into 6 TBI groups. TBI models were produced by the modified method of Feeney. After the impact, ICP of each subject was recorded continuously by an ICP monitor until the animal was sacrificed at scheduled time. The apoptotic brain cells were detected by an terminal deoxynucleotide-transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay. Cerebral water content (CWC) was measured with a drying method and calculated according to the Elliott formula. Then, an analysis was conducted to determine the correlation between the count of apoptotic cells and the clinical pathological changes of the brain. Results: Apoptotic cell count began to increase 2 h after the impact, and reached its maximum about 3 days after the impact. The peak value of CWC and ICP appeared 1 day and 3 days after the impact, respectively. Apoptotic cell count had a positive correlation with CWC and ICP. Conclusions: In TBI, occurrence of brain edema and ICP increase might lead to apoptosis of brain cells. Any therapy which can relieve brain edema and/or decrease ICP would be able to reduce neuron apoptosis, thereby to attenuate the secondary brain damage.

Effects of ganglioside GM1 on reduction of brain edema and amelioration of cerebral metabolism after traumatic brain injury

Objective: To observe the effects of ganglioside GM1 on reduction of brain edema and amelioration of cerebral metabolism after traumatic brain injury (TBI). Methods: An acute experimental closed TBI model in rats was induced by a fluid percussion brain injury model. At five and sixty minutes after TBI, the animals were intraperitoneally injected by ganglioside GM1 (30 mg/kg) or the same volume of saline. At the 6th hour after TBI, effects of ganglioside GM1 or saline on changes of mean arterial pressure (MAP), contents of water, lactic acid (LA) and lipid peroxidation (LPO) in the injured cerebral tissues were observed. Results: After TBI, MAP decreased and contents of water, LA and LPO increased in brain injury group; however, MAP was back to normal levels and contents of water, LA and LPO decreased in ganglioside GM1 treated group, compared with those in brain injury group (P< 0.05 ). No significant difference between the saline treated group and the brain injury group (P> 0.05 ) was observed.Conclusions: Ganglioside GM1 does have obvious neuroprotective effect on early TBI.

Human neuronal apoptosis secondary to traumatic brain injury and the regulative role of apoptosis-related genes

Objective: To observe human neuronal apoptosis secondary to traumatic brain injury, and to elucidate its regulative mechanism and the change of expression of apoptosis-related genes. Methods: Specimens of brain were collected from cases of traumatic brain injury in humans. The histological and cellular morphology was examined by light and electron microscopy. The extent of DNA injury to cortical neurons was detected by using TUNEL. By in situ hybridisation and immunohistochemistry the mRNA changes and protein expression of Bcl-2, Bax, p53, and caspase 3 p20 subunit were observed. Results: Apoptotic neurons appeared following traumatic brain injury, peaked at 24 hours and lasted for 7 days. In normal brain tissue activated caspase 3 was rare, but a short time after trauma it became activated. The activity peaked at 20-28 hours and remained higher than normal for 5-7 days. There was no expression of Bcl-2 mRNA and Bcl-2 protein in normal brain tissue but 8 hours after injury their expression became evident and then increased, peaked at 2-3 days and remained higher than normal for 5-7 days. The primary expression of Bax-mRNA and Bax protein was high in normal brain tissue. At 20-28 hours they increased and remained high for 2-3 days; on the 7th days they returned to a normal level. In normal brain tissue, p53mRNA and P53 were minimally expressed. Increased expression was detected at the 8th hour, and decreased at 20-28 hours but still remained higher than normal on the 5th day. Conclusions: Following traumatic injury to the human brain, apoptotic neurons appear around the focus of trauma. The mRNA and protein expression of Bcl-2, Bax and p53 and the activity of caspase 3 enzyme are increased.

Aquaporin-4 and traumatic brain edema

Brain edema leading to an expansion of brain volume has a crucial impact on morbidity and mortality following traumatic brain injury as it increases intracranial pressure, impairs cerebral perfusion and oxygenation, and contributes to additional ischemic injuries. Classically, two major types of traumatic brain edema exist： ＂vasogenic＂ and ＂cytotoxic/cellular＂. However, the cellular and molecular mechanisms contributing to the development/resolution of traumatic brain edema are poorly understood and no effective drugs can be used now. Aquaporin-4 （AQP4） is a water-channel protein expressed strongly in the brain, predominantly in astrocyte foot processes at the borders between the brain parenchyma and major fluid compartments,including cerebrospinal fluid and blood. This distribution suggests that AQP4 controls water fluxes into and out of the brain parenchyma. In cytotoxic edema, AQP4 deletion slows the rate of water entry into brain, whereas in vasogenic edema, AQP4 deletion reduces the rate of water outflow from brain parenchyma. AQP4 has been proposed as a novel drug target in brain edema. These findings suggest that modulation of AQP4 expression or function may be beneficial in traumatic brain edema.