Effects of electro-acupuncture on Noxa and caspase-3 expression in hippocampal CA1 region of a vascular dementia rat model

BACKGROUND:Noxa, a pro-apoptotic member of the Bcl-2 protein family, has been shown to induce the mitochondrial pathway of apoptosis and to mediate hypoxic cell death in a rat model of cerebral ischemia. This suggests that Noxa could participate in apoptosis during vascular dementia (VD). OBJECTIVE: To detect Noxa and caspase-3 expression after electro-acupuncture in VD rats to further validate the mechanism of electro-acupuncture-induced effects in the treatment of VD. DESIGN, TIME AND SETTING: A randomize...     

Effect of electroacupuncture on the expression of mTOR and eIF4E in hippocampus of rats with vascular dementia

Clinically, electroacupuncture is proved to be an effective therapy for vascular dementia; however, their mechanisms remain uncertain. The aim of the current study was to investigate the mechanism of electroacupuncture therapy for vascular dementia. One month after a vascular dementia animal model was established by bilateral occlusion of common carotid arteries, electroacupuncture treatment was given at “Baihui” (DU20), “Dazhui” (DU14), and “Shenshu” (BL23). Morris water maze was used to assess the learning and memory ability of rats. Western blot assay was performed to detect the expression of mammalian target of rapamycin (mTOR) and eukaryotic translation initiation factor 4E (eIF4E) in hippocampus of rats. Morris water maze test showed that electroacupuncture improved the learning ability of vascular dementia rats. Western blot assay revealed that the expression level of mTOR and eIF4E in the electroacupuncture group and sham-operated group was higher than that in the vascular dementia group (P < 0.05). In conclusion, the decreasing expression of mTOR and eIF4E plays important roles in the pathogenesis of vascular dementia. Electroacupuncture improves learning and memory ability by up-regulating expression of mTOR and eIF4E in the hippocampus of vascular dementia rats.     

Effects of electroacupuncture on the expression of p70 ribosomal protein S6 kinase and ribosomal protein S6 in the hippocampus of rats with vascular dementia

This study investigated the mechanism underlying electroacupuncture therapy for vascular dementia through electroacupuncture at the acupoints of Baihui (DU20), Dazhui (DU14), and bilateral Shenshu (BL23) in a rat model of vascular dementia produced by bilateral middle cerebral artery occlusion. Morris water maze test showed that electroacupuncture improved the learning ability of vascular dementia rats. Western blot assay revealed that the expression of p70 ribosomal protein S6 kinase and ribosomal protein S6 in vascular dementia rats was significantly increased after electroacupuncture, compared with the model group that was not treated with acupuncture. The average escape latency was also shortened after electroacupuncture, and escape strategies in the spatial probe test improved from edge and random searches, to linear and trending swim pathways. The experimental findings indicate that electroacupuncture improves learning and memory ability by up-regulating expression of p70 ribosomal protein S6 kinase and ribosomal protein S6 in the hippocampus of vascular dementia rats.     

纳洛酮改善东莨菪碱所致大鼠空间工作记忆障碍的神经机制研究

目的　对纳洛酮改善东莨菪碱所致大鼠空间工作记忆障碍的神经机制进行探索。目的　对纳洛酮改善东莨菪碱所致大鼠空间工作记忆障碍的神经机制进行探索。方法　大鼠随机分成三组:正常组、东莨菪碱组和纳洛酮治疗组,采用Morris水迷宫延缓性匹配任务试验记录每只大鼠前后两次逃避潜伏期的时间。利用免疫组化及图像分析技术,定量测定各组大鼠海马和前额叶皮层胆碱乙酰转移酶(ChAT)合成,利用电子显微镜技术,观察大鼠海马CA1区超微结构的改变。结果　(1)前后两次逃避潜伏期在正常组呈极显著性差异(t =7.32, P =0.00),东莨菪碱组无差异 (t =1.01, P =0.35),纳洛酮治疗组呈显著性差异(t =3.19, P =0.02)。(2)各组大鼠海马CA1、CA3区, 前额叶皮层神经元ChAT量无差别(P >0.05)。(3)各组大鼠锥体细胞胞体超微结构正常,但东莨菪碱组CA1区神经元突触超微结构明显改变。结论　M-型胆碱能受体阻滞剂东莨菪碱能损害大鼠空间工作记忆;阿片受体阻滞剂纳洛酮能够改善这种损害,其神经机制并非是增加 ChAT活性,而是能促进神经元突触囊泡Ach向突触间隙大量释放,及增加突触后致密物质密度。     

米诺环素改善血管性痴呆大鼠认知功能障碍的机制研究

目的探索米诺环素是否在血管性痴呆导致的认知功能损害发生发展中发挥一定的神经保护作用,并进一步分析参与其中的相关分子机制。 方法SD大鼠随机分为假手术组、模型组和米诺环素治疗组。结扎双侧颈总动脉建立大鼠血管性痴呆模型,术后腹腔注射米诺环素（25,50 mg/kg）,28 d后进行水迷宫行为学实验检测认知变化,HE染色和Western blotting分析大鼠海马神经细胞凋亡的相关机制。 结果（1）水迷宫认知功能测试显示,米诺环素能够显著缩短血管性痴呆大鼠寻找平台的潜伏期,并且明显延长在目标象限的停留时间,P<0.05为差异具有统计学意义。（2）HE染色显示米诺环素能够显著减轻模型组大鼠海马神经细胞损伤。（3）米诺环素治疗组含半胱氨酸的天冬氨酸蛋白水解酶-3（Caspase-3）蛋白表达水平及Bax/Bcl-2比值较模型组明显下降,P<0.05为差异具有统计学意义。（4）与模型组相比,米诺环素组磷脂酰肌醇3-激酶（PI3K）及磷酸化蛋白激酶B（p-AKT）蛋白表达水平明显升高,磷酸化糖原合酶激酶-3β（p-GSK-3β）蛋白表达却显著下降,P<0.05为差异具有统计学意义。 结论米诺环素通过激活PI3K/AKT信号通路,抑制该通路下游靶分子GSK-3β活性,减少海马神经细胞凋亡的发生,在神经细胞保护和改善认知功能障碍中发挥重要作用。     

Apocynin attenuate spatial learning deficits and oxidative responses to intermittent hypoxia

Rationale: The long-term intermittent hypoxia (LTIH) that characterizes sleep-disordered breathing impairs spatial learning and increases oxidative stress in rodents. We hypothesized that LTIH activated brain NADPH oxidase, which served as a critical source of superoxide in the oxidation injury, and that apocynin might attenuate LTIH-induced spatial learning deficits by reducing LTIH-induced NADPH oxidase expression. Objective: To investigate the effects of apocynin on spatial learning and oxidative responses to LTIH in rats. Methods: Forty healthy male Sprague–Dawley (SD) rats were randomly divided into four groups of 10 each: a LTIH group, an apocynin-treated LTIH group, a sham LTIH group and an apocynin-treated sham group. Spatial learning in each group was assessed with the Morris water maze test. RT-PCR and Western blot were used to examine mRNA and protein expression of NADPH oxidase subunit p47phox and p22phox in the hippocampus region. The level of MDA and SOD were detected by colorimetric method. The terminal deoxynucleotidyl transferase-mediated dUTP-nick end-labeling (TUNEL) method was used to display the apoptotic cells of the hippocampus tissue. Results: Apocynin treatment prevented LTIH-induced decreases in spatial learning during the Morris water maze as well as LTIH-induced decrease in SOD levels. In untreated animals, LTIH exposure was related to increase of MDA levels in comparison to sham LTIH animals, and apocynin-treated animal exposure to LTIH showed reduction in MDA levels. Increases in hippocampus NADPH oxidase subunit p47phox mRNA and protein expression were observed in LTIH-exposed animals; there was no statistical difference of p47phox mRNA and protein expression between LTIH group and apocynin treatment group. Treatment with apocynin significantly ameliorated cell apoptosis in LTIH-exposed animals. Conclusion: These results indicate that apocynin attenuates LTIH-induced spatial learning deficits and mitigates LTIH-induced oxidative stress through multiple beneficial effects on oxidant pathways. NADPH oxidase up-expression is closely associated with oxidative processes in LTIH rats, and inhibition of NADPH oxidase activity may hopefully serve as a useful strategy for cognitive function impairment from chronic intermittent hypoxia.     

海马锥体细胞的变化对血管性痴呆大鼠学习记忆能力的影响

目的研究海马锥体细胞的变化对血管性痴呆大鼠学习记忆能力的影响。方法将大鼠随机分成手术组及对照组,手术组制作血管性痴呆大鼠模型,30d后用Morris水迷宫检测两组大鼠学习记忆能力及HE染色检测海马锥体细胞数目的变化。结果手术组大鼠学习记忆能力明显下降,海马锥体细胞数目较对照组明显减少。结论血管性痴呆大鼠海马锥体细胞减少,学习记忆能力下降。     

γ-氨基丁酸对慢性脑缺血致血管性痴呆大鼠学习记忆能力的影响

目的观察γ-氨基丁酸（GABA）对慢性脑缺血致血管性痴呆（VD）大鼠学习记忆能力及海马CA1区神经元形态学的影响。方法将SD大鼠随机分为假手术组、模型组、GABA组,采用双侧颈总动脉永久性结扎法建立VD模型。GABA组术后腹腔注射GABA0.5g.kg-1.d-1,连续注射60d;用Morris水迷宫实验检测大鼠空间学习记忆能力;Nissl染色观察大鼠海马CA1区神经元形态学变化。结果 GABA能明显改善VD大鼠学习记忆能力,也能减轻海马CA1区神经元损伤。结论 GABA能改善慢性脑缺血致VD大鼠的学习记忆能力,减轻海马神经元损伤可能是其机制之一。     

Cerebrolysin improves memory and ameliorates neuronal atrophy in spontaneously hypertensive,aged rats

The spontaneously hypertensive (SH) rat has been used as an animal model of vascular dementia (VD). Our previous report showed that, SH rats exhibited dendritic atrophy of pyramidal neurons of the CA1 dorsal hippocampus and layers 3 and 5 of the prefrontal cortex (PFC) at 8 months of age. In addition, we showed that cerebrolysin (Cbl), a neurotrophic peptide mixture, reduces the dendritic atrophy in aged animal models. This study aimed to determine whether Cbl was capable of reducing behavioral and neuronal alterations, in old female SH rats. The level of diastolic and systolic pressure was measured every month for the 6 first months and only animals with more than 160 mm Hg of systolic pressure were used. Female SH rats (6 months old) received 6 months of Cbl treatment. Immediately after the Cbl treatment, two behavioral tests were applied, the Morris water maze test for memory and learning and locomotor activity in novel environments. Immediately after the last behavioral test, dendritic morphology was studied with the Golgi‐Cox stain procedure followed by a Sholl analysis. Clearly, SH rats with Cbl showed an increase in the dendritic length and dendritic spine density of pyramidal neurons in the CA1 in the dorsal hippocampus and layers 3 and 5 of the PFC. Interestingly, Cbl improved memory of the old SH rats. Our results support the possibility that Cbl may have beneficial effects on the management of brain alterations in an animal model with VD. Synapse 70:378–389, 2016 . © 2016 Wiley Periodicals, Inc.     

Juvenile Taiep rats have shorter dendritic trees in the dorsal field of the hippocampus without spatial learning disabilities

Myelin mutant taiep rats show a progressive demyelination in the central nervous system due to an abnormal accumulation of microtubules in the cytoplasm and the processes on their oligodendrocytes. Demyelination is associated with electrophysiological alterations and the mutant had a progressive astrocytosis. The illness is associated with change in cytokine levels and in the expression of different nitric oxide synthase and concomitantly lipoperoxidation in several areas of the brain. However, until now there has been no detailed anatomical analysis of neurons in this mutant. The aim of this study was to analyze the dendritic morphology in the hippocampus using Golgi‐Cox staining and spatial memory through Morris water maze test in young adult (3 months old) taiep rats and compare them with normal Sprague‐Dawley. Our results showed that taiep rats have altered dendritic tree morphology in pyramidal neurons in the CA1 field of the hippocampus, but not in the CA3 region. These morphological changes did not produce a concomitant deficit in spatial memory acquisition or recall at this early stage of the disease. Our results suggest that impairment of dendritic morphology in the CA1 field of the hippocampus is a landmark of the pathology of this progressive multiple sclerosis model.     

金纳多对血管性痴呆大鼠认知功能及生长抑素表达的影响

目的研究金纳多对血管性痴呆(vascular dementia,VD)大鼠认知功能及生长抑素(SS)表达的影响。方法采用结扎双侧颈总动脉方法制备慢性前脑缺血动物模型。将100只老龄大鼠随机分为假手术组、模型组和金纳多组。应用水迷宫及免疫组化方法对各组大鼠学习记忆及SS表达进行观察。结果模型组与假手术组学习记忆能力差异有统计学意义(P<0.05);与模型组比较,金纳多治疗30 d后大鼠学习记忆能力明显改善(P<0.05),SS阳性神经元表达增加(P<0.05)。结论金纳多可增加SS阳性神经元表达,改善VD大鼠学习记忆能力。     

Hippocampal function in the rat: Cognitive mapping or vicarious trial and error?

The most prominent hypothesis of hippocampal function likens the hippocampus to a “cognitive map,” a term used by a famous learning theorist, E. C. Tolman, to explain maze learning. The usual application of this concept of cognitive map, as it applies to the hippocampus, is to what is called spatial learning, mainly in the radial-arm maze of Olton and the Morris water maze. In a recent Hippocampus Forum, evidence for the cognitive map hypothesis was reviewed in a lead article by Nadel, followed by a series of commentaries by leading investigators of hippocampal function. This speculative commentary offers an alternative not represented in the forum—that the function of the hippocampus in spatial learning is not as a cognitive map, but that it subserves another function proposed by Tolman in his work on simple discrimination learning, vicarious trial and error, based on incipient, conflicting dispositions to approach and avoid.     

高剂量灵芝孢子粉干预戊四氮致痫模型大鼠海马及皮质区神经细胞Bcl-2、Bax的表达

采用中药灵芝孢子粉低、中、高剂量（150, 300, 450 mg/kg）干预戊四氮致癫痫模型28 d，并设空白对照组。经免疫组织化学染色和TUNEL检测后发现，与模型相比，灵芝孢子粉高剂量组大鼠海马和皮质区神经细胞TUNEL阳性细胞数及Bax阳性细胞数均减少，而Bcl-2阳性表达细胞数增加。Morris水迷宫实验检测结果显示，灵芝孢子粉高剂量组大鼠逃避潜伏期缩短，跨过原平台次数增加。说明高剂量灵芝孢子粉上调癫痫模型大鼠海马和皮质区神经细胞Bcl-2蛋白的表达，抑制Bax免疫反应及癫痫所致的神经细胞凋亡，明显改善其学习记忆功能。     

慢性应激对大鼠学习记忆功能和海马神经细胞粘附分子表达的影响

目的观察慢性应激对大鼠学习记忆功能和海马神经细胞粘附分子（NCAM）表达的影响，探讨海马NCAM表达在慢性应激影响学习记忆机制的作用。方法20只SD大鼠随机被分为对照组（10只）和慢性应激组（10只），后者以束缚浸水应激方式连续应激21天，三周后行水迷宫实验，并用免疫组化法测定大鼠的脑海马区NCAM的表达。结果应激组在水迷宫测试中寻找水中隐藏平台的潜伏期为（7．1±8．9）秒，对照组为（12．3±4．2）秒，差异有统计学意义；穿越平台次数：应激组为（8．4±1．1）次，对照组为（12．5±1．9）次，差异有统计学意义。应激组海马CA3区NCAM的表达：25．2％±3．6％，对照组为37．9％±5．1％，差异有统计学意义。结论慢性应激对大鼠的学习记忆功能有抑制作用。其机制可能与应激抑制海马CA3区NCAM表达有关。     

癫痫持续状态对发育期大鼠认知功能的影响及cAMP/PKA信号通路所起作用

目的 探讨癫痫持续状态(SE)对发育期大鼠认知功能的影响及环磷酸腺苷/蛋白激酶A(cAMP/PKA)信号转导通路在其中所起的作用.方法 SD大鼠32只按照完全随机数字表法分为SE组、生理盐水(NS)组,每组16只.戊四氮(PTZ)诱导大鼠SE,Morris水迷宫和Y迷宫实验观察大鼠学习记忆功能的改变,放射免疫分析法测定海马组织cAMP的含量,免疫组织化学方法检测海马各区PKA的表达.结果 SE组大鼠在Morris水迷宫中平均逃避潜伏期延长,原平台所在象限的游泳时间缩短,与NS组比较差异有统计学意义(P<0.05).在Y迷宫中达标所需的训练次数增多,24 h记忆保持率下降,与NS组比较差异有统计学意义(P<0.05).NS组大鼠海马cAMP的含量为(280.38±22.66)pmol/g,SE组为(147.25±16.83)pmol/g,差异有统计学意义(P<0.05).SE组CA3区和CA1区PKA的表达较NS组明显减少.结论 SE可以导致发育期大鼠认知功能障碍,其机制可能与cAMP/PKA信号转导通路的功能受损有关.

Abstract：

Objective To observe the influence of status epilepticus (SE) on cognitive function of immature rats and explore the role of hippocampal cAMP/PKA signaling pathway in cognitive function impairment of immature rats. Methods Immature male SD rats were assigned randomly to 2 groups: SE group, induced by intraperitoneal injection of pentylenetetrazole (PTZ, n=16), and normal saline control group (n=16). Learning and memory tests using the Morris water maze and Y-maze were performed 7 d after SE. After testing, alterations of content of cAMP were detected by radioimmunoassay,and the expression of PKA in the hippocampus was examined by immunohistochemistry. Results SE rats exhibited learning and memory deficits in the Morris water maze and Y-maze tests: as compared with those in the controls in Morris water maze, the mean escape latency of searching the platform obviously prolonged and the swimming time in the original platform region significantly shortened in SE rats (P<0.05); as compared with those in the controls in Y maze, the number of standard training times obviously increased and the rate of retention of memory significantly decreased in SE rats (P<0.05). At the same time, the cAMP content in hippocampus of SE rats ([147.25±16.83] pmol/g) was significantly lower as compared with that in controls ([280.38±22.66] pmol/g), and the expression of PKA in the CA3 and CA1 areas within hippocampal area of SE rats was obviously decreased as compared with that in controls (P<0.05). Conclusion SE could result in learning and memory deficits in immature rats, which may be related to the impairment of hippocampal cAMP/PKA signaling pathway.     

Immunocytochemical study on the distribution of p53 in the hippocampus and cerebellum of the aged rat

A role for p53-mediated modulation of neuronal viability has been suggested by the finding that p53 expression is increased in damaged neurons in models of ischemia and epilepsy. P53 gene upregulation precedes apoptosis in many cell types, and a potential role for this molecule in apoptosis of neurons has already been demonstrated in Alzheimer's disease. Recent studies suggest that p53-associated apoptosis may be a common mechanism of cell loss in several important neurodegenerative diseases. In the present study, we examined changes in p53-immunoreactive (IR) neurons in the brains of aged rats for the first time employing immunocytochemical and in situ hybridization methods. P53-IR neurons were found in the CA1 region of hippocampus, septal region and cerebellum in the aged rats, but there was no p53-IR cell in the brains of adult rats. In the hippocampus of the aged rat, p53-IR cells predominated in the stratum oriens and pyramidal layers, while the molecular layer contained relatively few p53-IR cells. The most prominent population of immunoreactive labeling in cerebellar cortex was localised within the cell bodies of Purkinje cells and dendrites in molecular layers. Upregulation of p53 in the Purkinje cells observed in this study suggests that significant loss of Purkinje cells with aging may be regulated with several apoptosis-controlling factors including p53 and oxidative stress mechanism. Further investigations are required to establish whether direct functional relations exist between p53 and the apoptotic neuronal death in normal aging or Alzheimer brains.     

血管性痴呆小鼠海马组织学改变及乙酰胆碱酯酶活性变化特征

目的:探讨血管性痴呆(VD)小鼠海马组织病理学改变及乙酰胆碱酯酶病理(AchE)活性的变化特征.方法:将50只小鼠随机分为假手术组和模型组。模型组采用双侧颈总动脉反复缺血再灌注法制备VD模型,术后第29天和第30天测试学习记忆成绩,术后第30天检测海马CA1区组织学变化及AchE含量。结果:VD模型组小鼠学习记忆成绩较假手术组明显下降;海马CA1区锥体细胞数目减少,细胞核体积变小;且模型组小鼠海马AchE活性明显低于假手术组(P<0.01)。结论:小鼠海马组织内的AchE活性下降参与了VD的形成,进一步导致VD小鼠的学习和记忆障碍。     

Genistein attenuates cognitive deficits and neuroapoptosis in hippocampus induced by ketamine exposure in neonatal rats

Ketamine is a frequently used anesthetic in pediatric patients that can cause cognitive impairment. Genistein, a bioactive component of soy products, has been shown to suppress neuronal death through regulating the expression of apoptosis related genes. In this study, we hypothesized that genistein could alleviate ketamine‐induced cognitive impairment by ameliorating hippocampal neuronal loss and tested this hypothesis in rats. Neonatal rats were treated with ketamine and genistein. Hippocampal tissue was harvested for histological and biochemical analysis to determine neuronal apoptosis and proteins involved in the apoptotic pathways. Behavioral assays including contextual fear conditioning test and Morris water maze test were performed to assess cognitive functions, including learning and memory. We found that in fear conditioning test, genistein restored freezing time in ketamine treated rats in a dose dependent manner. Similarly, genistein attenuated impaired learning and memory in Morris water maze test in rats treated with ketamine. Additionally, ketamine‐induced neuronal apoptosis in rat hippocampus was attenuated by genistein treatment. Finally, we found that genistein partially restored proteins associated with apoptosis, including Bax, Bcl‐2, cleaved caspase 3, and phosphorylated GSK‐3ß and Akt. Genistein suppresses hippocampal neuronal loss and cognitive disruption induced by ketamine in rats.     

咖啡因对慢性低O2高CO2大鼠学习记忆及N-甲基-D-天冬氨酸受体亚基1 mRNA表达的影响

目的：探讨咖啡因对慢性低O2高CO2处理的大鼠空间学习记忆、皮质和海马N-甲基-D-天冬氨酸受体（NMDAR）亚基1mRNA（NR1 mRNA）表达的影响。方法：SD大鼠48只分为4组,正常对照组;低O2高CO24周（HH）组,处理组：低O2高CO2＋咖啡因0．1mg·mL^-14周（HCl组）,低O2高CO2＋咖啡因0．3mg·mL^-14周（HC2组）。处理组以咖啡因水溶液干预4周后行Morris水迷宫实验,观察大鼠寻找站台的平均逃避潜伏期和游泳总距离;采用原位杂交法观察大鼠海马及皮质区NRImRNA的表达与分布情况。结果：①Morris水迷宫实验显示,HH组与对照组相比大鼠寻找站台的平均逃避潜伏期延长、游泳总距离增加（P〈0．05）,HC2组有显著性降低（P〈0．05）;②原位杂交显示NR1 mRNA阳性细胞广泛分布于海马和皮质区;模型组与对照组比较大鼠海马锥体细胞层NR1 mRNA表达的平均吸光度值降低（P〈0．05）,而咖啡因处理组平均吸光度值升高。结论：咖啡因可改善慢性低O2高CO2大鼠的空间学习记忆能力并增加海马和皮质区NR1 mRNA的表达。     

Positive and negative modulation of the GABAA receptor and outcome after traumatic brain injury in rats

Glutamate-mediated excitotoxicity has been shown to contribute to cellular dysfunction following traumatic brain injury (TBI). Increasing inhibitory function through stimulation of γ-aminobutyric acid (GABA_A) receptors may attenuate excitotoxic effects and improve outcome. The present experiment examined the effects of diazepam, a positive modulator at the GABA_A receptor, on survival and cognitive performance in traumatically brain-injured animals. In experiment 1, 15 min prior to central fluid percussion brain injury, rats (n=8 per group) were injected (i.p.) with saline or diazepam (5 mg/kg or 10 mg/kg). Additional rats (n=8) were surgically prepared but not injured (sham-injury). Rats pre-treated with the 5 mg/kg dose of diazepam had significantly lower mortality (0%) than injured, saline-treated rats (53%). Also, diazepam-treated (5 mg/kg) rats had significantly shorter latencies to reach the goal platform in the Morris water maze test performed 11–15 days post-injury. In experiment 2, at 15 min post-injury, rats were given either saline (n=5) or 5 mg/kg diazepam (n=6). Rats treated with diazepam did not differ in mortality from injured rats treated with vehicle. However, rats treated with diazepam at 15 min post-injury had significantly shorter latencies to reach the goal platform in the Morris water maze than injured, vehicle-treated rats. In experiment 3, the post-injury administration of bicuculline (1.5 mg/kg, n=8), a GABA_A antagonist, increased Morris water maze goal latencies compared to injured animals treated with saline (n=8). These results suggest that enhancing inhibitory function during the acute post-injury period produces beneficial effects on both survival and outcome following experimental TBI.