Regeneration of the corticospinal tract (CST) is considered a therapeutic target to achieve improved recovery of motor function after spinal cord injury (SCI), which is an incurable CNS damage that affects millions of people. Exercise training is effective in improving multiple functions in spinal cord-injured patients. However, the effects of exercise training on axon regeneration have not been sufficiently reported. Osteopontin (OPN) has great potential application as a neuroprotective agent for the repair of the nervous system. Studies have shown that the extent of axon regeneration strongly correlates with the expression of OPN. Our previous studies demonstrated that treadmill exercise supplemented by OPN enhances motor function recovery, but axon regeneration is still limited. Extending the treadmill exercise for 12 weeks, we observed promoted axon regeneration, motor function improvement, and signaling pathway activation in mice with SCI after supplementing OPN. Axon regeneration was observed with an anterograde tracer, motor function recovery was evaluated by animal ethology and electrophysiology, and the levels of IGF-1R/Akt/mTOR signaling pathway were evaluated. The results showed that the CST of C5 crushed mice regenerated and formed synaptic connections with neurons after treadmill exercise supplemented by OPN, the horizontal ladder and cylinder rearing test of injured limbs were improved, motor evoked potential also suggested enhanced nerve conduction, and the expression of p-IR, p-Akt, and p-S6 were increased. And the improvements were more obvious than that of the exercise group. Collectively, our study found that treadmill exercise supplemented by OPN promote axon regeneration and motor function through the IGF-1R/Akt/mTOR signaling pathways, and these improvements can be inhibited by rapamycin and Methyl-beta-CD (M-B-CD).

Acute and chronic exposure to high altitude causes multiple negative neurological consequences. Further research has shown the efficacy of targeted drugs after acute hypoxia. However, the effects and mechanisms of physical therapy like exercise, on after exposed-induced myelin repair and functional improvements have remained unclear. Here, we explored the efficacy of treadmill training at different intensities on recovery in a rat model of acute hypobaric hypoxia (HH) injury. A 4-week treadmill training scheme was used at 30

Regulatory T (Treg) cells contribute to white matter repair following ischemic stroke, but their limited availability in circulation restricts their therapeutic potential. Exercise, as a non-invasive and effective rehabilitation method, has been shown to restore Treg balance in diseases. This study explores the effects of treadmill training on Treg upregulation and its influence on myelin repair and functional recovery in rats with middle cerebral artery occlusion (MCAO). After four weeks of treadmill training, we analyzed the proportion of Treg cells (Tregs), FOXP3 expression, and oligodendrocyte-related protein levels using flow cytometry, immunofluorescence, and Western blotting. Myelin structure was examined with transmission electron microscopy (TEM), while motor coordination and balance were assessed using the fatigue rotarod and CatWalk analysis systems. To further explore the role of Tregs, the FOXP3 inhibitor P60 was used to inhibit Treg activity. The findings of our study indicate that training on a treadmill supports the maturation of oligodendrocytes, leads to an increase in myelin-associated proteins and the thickness of myelin, and promotes the recovery of motor function. Inhibition of Treg activity diminished these benefits, highlighting Tregs’ key role in exercise-induced remyelination. These findings suggest that treadmill training facilitates myelin regeneration and functional recovery by upregulating Tregs, offering potential new strategies for stroke treatment.

Background and purpose Research to date has lacked definitive evidence to determine whether mirror therapy promotes the recovery of upper extremity function after stroke. Considering that previous studies did not stratify patients based on structural retention, this may be one of the reasons for the negative results obtained in many trials. The goal evaluates the efficacy of TBMT (utilizing an innovatively designed mirror) versus standard occupational therapy for stroke patient's upper limb functionality.Methods and analysis This single-center randomized controlled trial will involve 50 patients with stroke. All patients will be randomly assigned to either the task-based mirror therapy or the control group. The interventions will be performed 5 days per week for 4 weeks. The primary outcomes will be the mean change in scores on both the FMA-UE and modified Barthel Index (MBI) from baseline to 4 weeks intervention and at 12 weeks follow-up between the two groups and within groups. The other outcomes will include the Action Research Arm Test (ARAT), the Nine Hole Peg Test (9HPT), the Functional Independence Measure, and MRI.Discussion This trial will not only to establish that task-based mirror therapy (TBMT) could improve the recovery of hand function after stroke but also to explore the underlying mechanisms. We expect that this finding will clarify the brain activation and brain network mechanisms underlying the improvement of hand function with task-oriented mirror therapy and lead to new ideas for stroke hand function rehabilitation.Trial registration URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2300068855. Registered on March 1, 2023

Spinal cord injury (SCI) results in stalled motor function recovery under the chronic phase. One of the reasons due to the presence of ongoing inflammation. Therefore, regulating the status of immune cells may help reopen the window for neural repair, which represents a potential therapeutic target. In this study, we aimed to investigate whether this could be achieved in mice with cervical 5 crush CSCI (4 W) by utilizing a concentration of 0.5 mg/kg of lipopolysaccharide (LPS) to stimulate microglia/macrophages. Additionally, the mice underwent rehabilitation training for another 6 weeks. Our results showed that systemic injection of LPS enhanced the effects of forelimb rehabilitation training, as evaluated through single pellet grasping (SPG). Electrophysiological studies revealed the restoration of cortical drive to the injured side’s forelimb muscles in the training combined with LPS group. Tract tracing studies demonstrated the reconstruction of cortical innervation to the cervical spinal cord. Furthermore, the levels of pro-inflammatory phenotype markers, such as inducible nitric oxide synthase (INOS) and CD68, decreased, while the expression of anti-inflammatory phenotype markers, including arginase 1 (ARG-1) and CD206, increased. Importantly, this phenotypic switch in microglia/macrophages was accompanied by an increase in phagocytic activity markers as indicated by BODIPY + IBA1 + staining. Collectively, our data suggests that low-dose LPS improves the effects of rehabilitation training by regulating the phenotypic transformation of microglia/macrophages in CSCI. This study provides a fresh perspective and intervention direction for the clinical treatment of chronic spinal cord injuries.

Objective To investigate the effects of treadmill training on the repair of myelin structure of dorsal corticospinal tract (dCST) in mice with T10 spinal cord mild contusion. Methods Twelve adult C57/BL female mice were used to construct and verify the model of spinal cord mild contusion, and another 30 mice were randomly divided into 3 groups (n=10): sham group, spinal cord injury (SCI) group, and treadmill training group.The mice of SCI and treadmill training groups were given unilateral (left) spinal cord contusion, while the sham group was given laminectomy only.A 4-week training scheme was conducted for the treadmill training group 1 week after SCI surgery (parameters: 12 m/min, 30 min/session, 1 time/day, 5 d/week).The primary motor cortex (M1) of mice in each group was injected with biotinylated dextran amine (BDA) to trace dCST 2 weeks before sampling, followed by the collection of tissue samples when the 4-week training finished.Then the expression levels of platelet-derived growth factor receptor α(PDGFRα), Ki67 protein, oligodendrocyte transcription factor 2(Olig2), adenomatous polyposis coli protein (APC/CC1) and myelin basic protein (MBP) were detected by immunofluorescence assay.Transmission electron microscopy (TEM) was also used to observe the myelination in the left dCST area.Moreover, Basso Mouse Scale (BMS) was performed in each group to evaluate the motor function of left hindlimb before injury, 1 week after injury and 1, 2, and 4 weeks after training. Results Immunofluorescent labeling showed that the ratio of PDGFRα/Ki67 double positive cells to the total number of PDGFRα positive cells, the ratio of Olig2/APC/CC1 double positive cells to the total number of Olig2 positive cells, as well as the mean fluorescence intensity of MBP in the left dCST area of the SCI group were significantly lower than those of the sham group (P < 0.01), while these indexes were higher in the treadmill training group than in the SCI group (P < 0.01).TEM results indicated that the G-ratio of the left dCST area was elevated in the SCI group (P < 0.01), but was reduced greatly in the treadmill training group (P < 0.01).Finally, the BMS scores were improved in the treadmill group at each detection time point after injury, but there was no significant difference as compared with the SCI group (P>0.05). Conclusion Treadmill training can facilitate the proliferation and differentiation of oligodendrocytes precursor cells (OPCs), improve the maturation of oligodendrocytes (OLs) in the left dCST region, and increase the expression of myelin related proteins, thus promoting the repair of myelin structure after SCI in adult mice.

Previous studies reported that the codeletion of PTEN and SOCS3 can greatly enhance the capacity of axon regeneration after central nervous system (CNS) injury. Moreover, the promotion of functional recovery can be improved by rehabilitative training under a use-dependent plasticity mechanism after CNS injury. However, few studies have reported the interaction between these mechanisms after spinal cord injury (SCI). Therefore, we investigated the combined effects of PTEN/SOCS3 coinhibition and rehabilitative training on axon regeneration and upper extremity motor functional improvement after cervical SCI in mice. In this study, we used RNA interference viruses to coinhibit PTEN and SOCS3 and induced a C5 crush injury on the side of preference. The injured upper extremity was trained by single pellet grasping for 4 weeks. We found that the coinjection of viruses significantly increased the expression of p-S6 and p-STAT in the cortex, reduced the dieback pattern of injured axons and promoted traced axon regeneration. More importantly, combination therapy further enhanced axon regeneration compared with PTEN/SOCS3 coinhibition alone. In behavioral tests, the motor performance of the mice in the PTEN/SOCS3 + Training group was better than that of the mice in the other groups. These results indicate that combining task-based rehabilitative training with PTEN/SOCS3 coinhibition further promotes axon regeneration and significant improvement in forelimb skilled motor function after cervical SCI. Our findings provide new therapeutic insights into SCI treatment.

Growing evidence has proven the efficacy of physical exercise in remyelination and motor function performance after spinal cord injury (SCI). However, the molecular mechanisms of treadmill training on myelin repair and functional recovery after SCI have not yet been fully studied. Here, we explored the effect of treadmill training on upregulating peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α)-mediated myelin repair and functional recovery in a mouse model of thoracic T10 contusion injury. A 4-week treadmill training scheme was conducted on mice with SCI. The expression levels of oligodendrogenesis-related protein and PGC1α were detected by immunofluorescence, RNA fluorescence in situ hybridization and western blotting. Transmission electron microscopy (TEM) was used to observe myelin structure. The Basso Mouse Scale (BMS) and CatWalk automated gait analysis system were used for motor function recovery evaluation. Motor evoked potentials (MEPs) were also identified. In addition, adeno-associated virus (AAV)-mediated PGC1α knockdown in OLs was used to further unravel the role of PGC1α in exercise-induced remyelination. We found that treadmill training boosts oligodendrocyte precursor cells (OPCs) proliferation, potentiates oligodendrocytes (OLs) maturation, and increases myelin-related protein and myelin sheath thickness, thus impelling myelin repair and hindlimb functional performance as well as the speed and amplitude of nerve conduction after SCI. Additionally, downregulating PGC1α through AAV attenuated these positive effects of treadmill training. Collectively, our results suggest that treadmill training enhances remyelination and functional recovery by upregulating PGC1α, which should provide a step forward in the understanding of the effects of physical exercise on myelin repair.

This study aims to investigate the effect of insulin-like growth factor 1 (IGF-1) combined with osteopontin (OPN) on the protein expression levels and growth of neuronal axons and its possible mechanism. In this study, IGF-1 combined with OPN promoted neuronal axon growth through the IGF-1R/Akt/mTOR signaling pathway in lipid rafts, and the effect was better than that of either agent alone. This effect was suppressed when given the mTOR inhibitor rapamycin or the lipid raft cholesterol extraction agent methyl-β-cyclodextrin (M-β-CD). Rapamycin could inhibit the expression of phosphorylated ribosomal S6 protein (p-S6) and phosphorylated protein kinase B (p-Akt) and limit axon growth. In addition to the above effects, M-β-CD significantly downregulated the expression of phosphorylated insulin-like growth factor 1 receptor (p-IR). To further investigate the changes in lipid rafts when stimulated by different recombinant proteins, membrane lipid rafts were isolated to observe the changes by western blot. The expression levels of insulin-like growth factor 1 receptor (IR) and P-IR in the IGF-1 combined with OPN group were the highest. When M-β-CD was administered to the lipid rafts of neurons, the enrichment of IR by IGF-1 combined with OPN was weakened, and the p-IR was decreased. Our study found that IGF-1 combined with OPN could promote axon growth by activating the IGF-1R/Akt/mTOR signaling pathway in neuronal lipid rafts.

Abstract Treadmill exercise is beneficial for spinal cord injury (SCI) both in bench and in bedside, but the most effective treadmill exercise intensity and mechanisms underlying the treadmill exercise on skilled motor function recovery remain elusive. Here, the improved skilled motor function recovery, enhanced nerve conduction capability, neuroplasticity, and axonal sprouting were observed in the SCI mice after training for 4 weeks. However, high exercise intensity (HEI) leads to vulnerability and impaired exercise tolerance during training. We further found that in the moderate exercise intensity (MEI) and HEI groups showed elevated expression of brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1). Meanwhile, elevated phosphorylated levels of ribosomal protein S6 (p-S6) and protein kinase B (p-AKT) in mouse motor cortex were also observed, indicating the cortical mechanistic target of rapamycin (mTOR) pathway activation. To investigate the role of the cortical mTOR activation, we performed a rapamycin assay. After using rapamycin, the exercise-induced activation of the cortical mTOR pathway and the exercise-enhanced effects were inhibited. Together, the expression of neurotrophic factors and the activation of the cortical mTOR pathway are in an intensity-dependent manner. And the MEI is safer and more beneficial than the LEI and HEI. Based on the rapamycin assay, the exercise-induced activation of mTOR pathway is necessary for the enhanced motor cortex and spine remodeling, all of which further contribute to better-skilled motor function recovery. These dates may provide a new window to further understand the mechanisms underlying exercise training effects on the skilled motor function recovery following SCI.

Treadmill exercise is widely considered an effective strategy for restoration of skilled motor function after spinal cord injury (SCI). However, the specific exercise intensity that optimizes recovery and the underlying mechanistic basis of this recovery remain unclear. To that end, we sought to investigate the effect of different treadmill exercise intensities on cortical mTOR activity, a key regulator of functional recovery following CNS trauma, in an animal model of C5 crush spinal cord injury (SCI). Following injury, animals were subjected to treadmill exercise for 4 consecutive weeks at three different intensities (low intensity [LEI]; moderate intensity [MEI]; and high intensity [HEI]). Motor function recovery was assessed by horizontal ladder test, cylinder rearing test, and electrophysiology, while neurotrophic factors and cortical mechanistic target of rapamycin (mTOR) pathway–related proteins were assessed by Western blotting. The activation of the cortical mTOR pathway and axonal sprouting was evaluated by immunofluorescence and the changes of plasticity in motor cortex neurons were assessed by Golgi staining. In keeping with previous studies, we found that 4 weeks of treadmill training resulted in improved skilled motor function, enhanced nerve conduction capability, increased neuroplasticity, and axonal sprouting. Importantly, we also demonstrated that when compared with the LEI group, MEI and HEI groups demonstrated elevated expression of brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), phosphorylated ribosomal S6 protein (p-S6), and protein kinase B (p-Akt), consistent with an intensity-dependent activation of the mTOR pathway and neurotrophic factor expression in the motor cortex. We also observed impaired exercise endurance and higher mortality during training in the HEI group than in the LEI and MEI groups. Collectively, our findings suggest that treadmill exercise following SCI is an effective means of promoting recovery and highlight the importance of the cortical mTOR pathway and neurotrophic factors as mediators of this effect. Importantly, our findings also demonstrate that excessive exercise can be detrimental, suggesting that moderation may be the optimal strategy. These findings provide an important foundation for further investigation of treadmill training as a modality for recovery following spinal cord injury and of the underlying mechanisms.

髓鞘是包裹在轴突周围的多层绝缘膜.从少突胶质前体细胞的迁移和增殖,到有丝分裂后分化成未成熟的少突胶质细胞,再到成熟的少突胶质细胞髓鞘化是一个有规划的程序;而在许多髓鞘损伤疾病中,这一过程往往存在变异或进程受阻.过氧化物酶体增殖物激活受体γ亚型共激活因子1α(PGC-1α)属于核受体家族中的一员,主要调节机体能量代谢.PGC-1α在髓鞘形成和修复中发挥关键作用,其通过影响髓鞘基因和蛋白的表达,从而影响少突胶质谱系细胞的分化与成熟.本文就PGC-1α概述以及其在髓鞘发育和修复中的作用作简要综述,以期为治疗髓鞘损伤相关疾病提供研究思路.

目的 观察利用特定药物激活特定受体(DREADDs)技术提高大脑皮质神经元电活动对轻度脊髓损伤(SCI)小鼠轴突髓鞘再生及运动功能恢复的影响.方法 成年雄性C57/BL小鼠33只,皮质定向注射携带激活型DREADDs受体的腺相关病毒[AAV-hM3D(Gq)-mCitrine].随机分为假手术组、SCI组与激活组,每组11只.假手术组不损伤脊髓,SCI组与激活组制备SCI脊髓损伤模型,2周后,激活组腹腔注射1 mg/(kg·d)N-氧化氯氮平(CNO)以激活皮质神经元电活动,假手术组与SCI组腹腔注射等量生理盐水,1次/d,持续4周后灌注取材.采用免疫组织化学方法检测病毒感染情况以及神经元原癌基因(cFos)和髓鞘碱性蛋白(MBP)的表达;采用透射电镜观察背侧皮质脊髓束髓鞘化的程度;采用旷场试验BMS评分及不规则水平楼梯评估小鼠运动功能恢复情况.结果 免疫荧光染色证实腺相关病毒成功感染皮质锥体神经元,三组GFP标记的腺相关病毒转染神经元细胞数量差异无统计学意义(P>0.05).激活组小鼠皮质神经元cFos表达量明显增加,与SCI组和假手术组相比,差异有统计学意义(P<0.001);在脊髓损伤中心,激活组与假手术组轴突的MBP表达量明显高于SCI组,差异有统计学意义(P<0.001);透射电镜观察显示,激活组G-ratio值明显低于SCI组,差异有统计学意义(P<0.001);BMS评分结果显示,腹腔注射1、2、4周,三组BMS评分差异无统计学意义(P>0.05);不规则水平楼梯试验评估发现,腹腔注射2周,激活组与SCI组的错误率降低,且激活组的错误率明显低于SCI组(P<0.001);腹腔注射4周,激活组与SCI组的错误率持续下降,且激活组的错误率明显低于SCI组(P<0.001).结论 利用DREADDs技术提高大脑皮质神经元电活动能有效促进轻度脊髓挫裂伤后小鼠轴突的髓鞘再生及其技巧性运动功能的恢复.

Myocardial ischemia/reperfusion injury (MIRI) is the major cause of myocardial cell damage in acute myocardial infarction, and its treatment remains a clinical challenge. Ginsenoside Rb1 showed protective effects on the cardiovascular system; however, the underlying mechanism remains largely unclear. Effects of Ginsenoside Rb1 on rat MIRI-induced myocardial infarct size were evaluated through TTC staining. TUNEL assay and flow cytometry analysis were employed to estimate cell apoptosis. Apoptosis, autophagy and PI3K/Akt/mTOR pathway-related proteins were estimated via western blot. Expression of Beclin1 in myocardial tissues were examined by immunohistochemical analysis. Expression levels of IL-1[Formula: see text], TNF-[Formula: see text] and IL-6 were tested by enzyme-linked immunosorbent assay (ELISA). Here, we found that Ginsenoside Rb1 treatment not only alleviated MIRI in rats but also protected H9C2 cells against hypoxia/reoxygenation induced damage. Ginsenoside Rb1 abolished the MIRI-induced activation of autophagy. Meanwhile, we found that treatment of 3-MA (autophagy inhibitor) could enhance the protective effects of Ginsenoside Rb1 on H9C2 cells during H/R. Moreover, Ginsenoside Rb1 treatment resulted in the activation of the PI3K/Akt/mTOR pathway, and treatment of LY294002 (PI3K/Akt pathway repressor) abolished the protective effects of Ginsenoside Rb1 on myocardial in vitro and in vivo. Our results suggest that Ginsenoside Rb1 functions as a protector against MIRI by repressing cardiomyocyte autophagy through the PI3K/Akt/mTOR signaling pathway.

目的 探讨任务导向性康复训练对小鼠C5脊髓损伤后神经回路可塑性及前肢运动功能恢复的影响.方法 健康成年C75/BL小鼠21只随机数字表法分为假手术组、模型组、训练组,每组7只.模型组和训练组对C5脊髓进行左背侧及背外侧束钳夹损伤,假手术组仅剔除椎板.术后4周,训练组接受左侧前肢任务导向性康复训练4周.术前,术后3d、2周、4周、6周和8周行水平楼梯和圆筒攀爬探索测试.术后6周,采用生物素化葡聚糖胺(BDA)顺行示踪观察皮质脊髓束的轴突.术后8周,运动诱发电位检测左前肢的神经传导情况;免疫荧光双标BDA/神经元核特异蛋白(NeuN),观察病灶上段灰质前角内轴突出芽及与神经元的结构关系;免疫荧光双标NeuN/突触素I(Synapsin I),观察病灶处灰质前角内突触素的表达情况.结果 术后8周,模型组P1、N1潜伏期长于假手术组(P<0.05),训练组短于模型组(P<0.05).术后各时间点,与假手术组比较,模型组和训练组左前肢错误率升高,使用率下降(P<0.05);与模型组比较,术后6周和8周,训练组左前肢错误率降低(P<0.05),术后8周,训练组左前肢使用率升高(P<0.05).与模型组比较,训练组病灶上段灰质前角内轴突出芽增加,出芽轴突多与神经元共区域,Synapsin I表达增加(P<0.05).结论 任务导向性康复训练能促进脊髓损伤后局部神经回路可塑性变化,改善前肢运动功能.

脊髓损伤(spinal cord injury, SCI)是全球高发的中枢神经损伤性疾病,每年新增病例近80万[1].在其他治疗手段均未获得确切满意疗效的情况下,康复训练似乎是目前脊髓损伤患者的唯一选择.常用的康复训练(运动训练)方式有强制性运动训练、游泳训练、减重步行训练等.尽管在基础研究和临床应用方面进行了较多的研究,但其促进功能恢复的机制尚不完全清楚.本文拟总结近几年有关的最新进展,为今后研究提供参考.

An increasing number of studies connect neuronal activity with developmental myelination but how neuronal activity regulates remyelination has not been clarified. In this study, we induced the demyelination of the dorsal corticospinal tract (dCST) by a mild contusion spinal cord injury (SCI) on the T10 segment, and manipulated the neuronal activity of the primary motor cortex (M1) using chemogenetic viruses to induce activity and to suppress it. We found that oligodendrocyte precursor cell (OPC) proliferation and oligodendrocyte maturity following remyelination was strengthened after 4-week of neuronal activity stimulation. Furthermore, hindlimb motor function was also found to be improved. Vice versa, suppression of neuronal activity attenuated these effects. These results indicate that bidirectional regulation of neuronal activity can effectively modulate the development of oligodendrocyte lineage cells and the remyelination process. Neuronal activity supports the proliferation of OPCs, improves oligodendrocyte maturation and amplifies the axonal remyelination process, even though leads to better motor function recovery. Manipulation of neuronal activity in a non-invasive manner is therefore a promising avenue for exploration towards the treatment of central nervous system (CNS) demyelination diseases.

Transplantation of neural stem cells (NSCs) may be a potential strategy for traumatic brain injury treatment (TBI) due to their intrinsic advantages, such as cell replacement, secretion of neurotrophins and formation of functional synapses with host. However the underlying effects of transplanted NSCs on host micro-environment still need to be further elucidated. In this manuscript the effects of NSCs on release of neurotransmitter, survival of hippocampal neurons, reactivity of astrocytes and recovery of cognitive function after TBI were observed. The NSCs were isolated from cortex of neonatal Sprague-Dawley rat and then transplanted into injured brain regions caused by free-weight drop. The proliferation of astrocytes around injured sites were examined by GFAP immunofluorescent staining on 3, 7, 14 days after injury. The survival of neurons at CA1 regions of hippocampus toward contused regions was observed by HE staining on 3 and 14 days post-injury. The content of glutamic acid (Glu) and GABA in hippocampal tissues was examined on 1, 3, 7, 14, 28 days after injury by ELISA. On third day post-injury, hippocampal-dependent spatial memory was measured for 5 days without intermittent. NSCs in culture have the ability to proliferate and differentiate into different phenotypes of neural cells. After transplantation of NSCs, the proliferation of astrocytes around injured site was significantly inhibited compared to the injured group. At the same time the survival of neurons in hippocampal CA1 region were much more than those in injured group on 14 days post-injury. Meanwhile, the cognitive functions in NSC transplanted group was remarkably improved compared with injured group (p < 0.05). Furthermore, NSCs transplantation dramatically inhibited the release of Glu and maintained the content of GABA in injured hippocampal tissues on 1, 3, 7, 14, 28 days post-injury, which was of difference in statistics (p < 0.05). NSCs transplantation can effectively alleviate the formation of glial scar, enhance the survival of hippocampal neurons and improve cognitive function defects in rats with TBI. The underlying mechanism may be related to their effects on inhibiting the release of Glu and maintaining the content of GABA, so as to down-regulate excitotoxicity of neurotransmitter and improve the micro-environment in injured sites.