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Piao Zhang1#, Chao-Hui Liang1#, Di-ke Qiu1, Yuan Jin1, Cheng-Fei Bi1, Yu-Shi1, Liu-Lin Xiong2, Jia Liu1*
Ibrain 2016;2(4):153-160 Download
Backgroud: Spinal cord and cortex with conditioning leison are a kind of neurological trauma which seriously jeopardized the health of human beings. They are devastating for society and individuals, in part owing to the high rates of disability and resulting medical costs. BDNF is a vital molecular, which play a critical roel in the progress of spinal cord or cortex repairment. Interestingly, we found ERK1 pathway was involving in the regulating process. But regretfully, the possible mechanism is ambiguous. Methods: Hence, in order to illuminate the theory, we established the model with sciatic nerve and spinal cord transection. And then spinal cords and cortexes were harvested from rats with sciatic nerve and spinal cord transection for performing RT-PCR and Western Blot, which aimed to detect the level of BDNF and ERK1. Resluts: The results manifested that the expression of BDNF and ERK1 was higher in sciatic nerve transection and spinal cord transection group (RSNTASCT/LD) than sciatic nerve transection one. Conclusion: Here, we may draw a conclusion that spinal cord will restrain the level of BDNF, and sciatic nerve transection can promote ERK1 expression. Moreover, sciatic nerve transection and spinal cord transection will promote ERK1 expression. Nevertheless, sciatic nerve transection and spinal cord transection will promote BDNF and ERK1 expression, whilst sciatic nerve transection can restrain ERK1 expression in cortex. In our data, we are the first time to expound the role of endogenous BDNF relating to the regeneration of spinal cord in the condition of peripheral nerve injury, and reveal the possible underlying mechanism of ERK1 pathway, which may provide certain theoretical basis and experimental basis for the treatment of spinal cord injury and prognosis in clinic.
Xiu-Juan Dong#, Zhi-Wei Chen#, Xu-yin Yang, Long-Wang Zhang, Rui-Shen Xie, Jian Liu1, Feng-Mei Yuan1, Long Hui Zhou*, Zhen-Wu Sun1*
Ibrain 2016;2(1):9-17 Download
Background: Reduction of neurotrophic support in the aging brain is one of the possible mechanisms leading to the development of Alzheimer’s disease (AD). Until now no disease-modifying therapy is available for AD. It is imperative to develop effective therapy for AD. The following paper presented results showing that the transplant of NT-4 gene modified fibroblasts improved cognitive functions in AD rats, likely through the upregulation of BDNF. Methods: Hippocampal umbrella was bilaterally transected to produce a AD model involving chlinergic neuronal degeneration in the basal forebrain of rats. The NT-4 cDNA fragment, cloned from human NT-4 mRNA, was inserted into pcDNA3, then transformed into fibroblats derived from a green fluorescence protein (GFP) transgenic mouse. Then NT-4 gene-modified fibroblasts were transplanted into AD rats, and the behavior was tested by Morris water maze 1 months after cell transplantation. Results: Transplantation of NT-4 gene modified fibroblasts improved cognitive functions and protected cholinergic neurons from the loss of acetylcholine esterase immunoreactivity and upregulated BDNF gene expression. The protective effect of the transplantation on cholinergic neurons was lost in BDNF-knock-down mice. Conclusions: Our results have provided evidence that transplantation of NT-4 gene modified fibroblasts may protect transected cholinergic neurons and improve the cognitive functions in AD via upregulation of BDNF expression.
Zhuo Zhang1,2, Yan Yan2, Bin Sun2, Jia Liu3, Yu-Hong Zhu2*
Ibrain 2016;2(1):1-8 Download
Background: Effective therapy for the treatment of Alzheimer’s disease is far from satisfaction. Bone marrow stromal cells (BMSC) and neurotrophin-4 (NT-4), well known for the protection of cholinergic neuronal survival, are crucial for the treatment of AD, respectively. Combination treatment may be an attractive method for neural repair in AD patients. This study therefore investigated the effects of NT-4 gene modified bone marrow stromal cells on the cognitive ability and memory of AD rats, and explored the protective mechanism. Methods: Human NT-4 RNA was obtained and subjected to reverse transcriptase polymerase chain reaction, followed by recombinant reconstruction. Then, NT-4 gene was transferred into BMSC derived from a green fluorescence protein transgenic mouse. BMSC and NT-4 gene modified BMSC were separately transplanted into the hippocampus of AD rats. Three months after cell transplantation, behaviors and electro-physiology of the rats were assessed. The fate of BMSC in vivo and neuroprotective effect of NT-4 gene modified BMSC for hippocampus neurons was determined, also. Results: NT-4 gene modified BMSC could express high level of NT-4 and showed positive biological activity in vitro. After transplantation, the cognitive ability and electrophysiological elements like p50 of AD rats in the NT-4 gene modified BMSC group exhibited better improvement than in the BMSC group. Transplanted BMSC could survive and migrate in host hippocampus till three months, and increase the ratio number of CHAT positive neurons. Conclusions: Engrafted BMSC expressing NT-4 can survive, migrate and increase ChAT immunopositive neurons for the last function improvement in AD rats. BMSC carrying NT-4 could be as an effective strategy for AD treatment in future clinic trial.
Ping Dai1#, Lin Qin2,3#, Yuan Jin1, Yu Zhao1, Rong-Ping Zhang2*, Jin-Tao Li1*
Ibrain 2015;1(6):172-178 Download
Objective: Traumatic brain injury (TBI), a common neurosurgical disease, usually induces cognitive impairments, motor deficits, and neuropsychiatric deficits. Effective treatments are still lacking.  breviscapine shows broad pharmacological effects and facilitates functional recovery from cardiovascular and cerebrovascular insults, such as brain ischemia and myocardial ischemia. However,  the role of breviscapine in TBI remains vague. In this study, . we aimed to investigate whether breviscapine can improve functional deficits in rats with TBI. Method: Thirty adult female Sprague–Dawley (SD) rats were employed and randomly divided into three groups: sham group, TBI group, Breviscapine treatment group (Breviscapine+TBI). TBI was initiated using an electromagnetic-controlled cortical impact device. Breviscapine (0.375mg/kg) were administrated into lateral ventricles one time after TBI induction. Behavioral evaluation was conducted on days 2, 4, 6, 8,10, 12and 14 after TBI using mNSS tests,. At 14 days after operation, western blotting analysis, immunofluorescent staining and real-time RT-PCR were performed to evaluate the protein and mRNA level of netrin-1 in the brain tissues, respectively. Results: Compared with the sham rats, TBI deteriorated behavioral function indicated by increased mNSS (P<0.05). Breviscapine administration showed a significant decrease in mNSS compared to TBI group (P<0.05). Quantitative Real-time PCR showed the mRNA levels of netrin-1 in the TBI group were significantly decreased compared with the sham group, moreover, breviscapine treatment up-regulated netrin-1 mRNA in the brain when compared with the TBI group at day 8 post-injury (P<0.05). In addition,western blot analyses also showed breviscapine treatment up-regulated the protein level of netrin-1 in the brain when compared with the TBI group at day 8 post-injury (P<0.05).. Immunofluorescent staining of netrin-1 showed the same variation trend as the western blot. Conclusion: Breviscapine improves neurological function in rats with TBI probably by up-regulating netrin expression. This study would provide a potential therapeutical target for clinical therapy of TBI.
Ru-Xin Xing1#, Jing Liu2#, Liang-Liang Zhu1, Min Yang1, Liu-Lin Xiong2*, Yong-Jian Zhu1*
Ibrain 2015;1(5):141-149 Download
Background/aim: spinal cord injury (SCI), as leading causes of death and disability in worldwide, commonly threatens human health, and brings heavy burden to the family and the society, which is needing to develop new technique for the treatment of this diseases. Gene therapy, as conventional approaches to target certain pathophysiological process, has well been considered for biological therapy, but the efficiency is waiting to be improved. Here, we explore the effect of HSV BDNF releasing in local region in spinal cord injury condition. Methods: Adult Sprague–Dawley rats were randomly divided into sham group, SCT group, SCT-BDNF administrated group and SCT empty-vector group. After constructed the HSV-BDNF recombinant, they were transfected the motor neurons in the injured site of spinal cord. Moreover, stereology was used to determine the expression of BDNF in motor neurons. Meanwhile, the number of CD68 positive staining was detected to evaluate the inflammatory reaction in injected area. Lastly, BBB scores were utilized for assessing the motor function of hindlimbs. Results: HSV-BDNF recombinant was successfully constructed and transfected into neurons. BBB scores showed that HSV-BDNF administration could promote the improvement of hindlimb function, and HSV-BDNF injection can induce an inflammatory reaction, partly. These suggested that HSV-BDNF administration improve motor function and induce inflammation in injured spinal cord. Conclusions: The present results indicate that HSV-BDNF injection can promote the recovery of motor function and induce a slight inflammatory reaction in SCT rats. The mechanism may relate to the improvement of neuronal activity. The present findings therefore provides a novel therapeutic strategy for clinical treatment of SCI by releasing BDNF in local region.
Ru-Xin Xing1*, Liang-Liang Zhu1, Min Yang1, Fei Liu2*
Ibrain 2015;1(5):136-140 Download
Spinal cord injury is a prevalent disease in surgical clinic with a high morbidity and mortality. Due to its complex pathological process, there is no satisfied strategies for its repair. BDNF, an important member of neurotrophin family, is crucial in supporting survival and differentiation of neurons. However, the concentration of BDNF in CNS is very low, so as to not reach an effective level for the treatment. It therefore needs to develop new strategy to increase BDNF release in injury region. Human simple herpes virus(HSV), a neural invasion virus, has been developed as a vector to carry bio-factors into organism. Here, adult SD rats are divided into sham, SCT, and SCT with HSV-BDNF administrated group. The effect of HSV-BDNF recombinant infection on motor function recovery evaluated by BBB scale was detected, and labeled cells of HSV is observed under fluorescence microscope, as well as the BDNF expression level is evaluated using Western Blot and IHC. As the result, HSV-BDNF recombinant is detected in motor neurons from spinal cord tissue, and the level of BDNF substantially is increased. Finally, motor function recovery of rats in HSV-BDNF group is significantly improved, compared with the SCT group, which confirmed HSV-BDNF releasing in skeleton muscle could be as an effective strategy for the treatment of SCI.
Zhi-Wei Chen#, Xiu-Juan Dong#, Rui-Shen Xie, Xu-yin Yang, Long-Wang Zhang, Long-Hui Zhou, Feng-Mei Yuan, Hang-Ping Wang, Shu-Hua Song*, Jian Liu*
Ibrain 2015;1(3):75-83 Download
Background/aim: To construct recombinant vector of over expression and siRNA of Homo sapiens dihydropyrimidine 2 (Dpysl2) gene. Methods: Fragment containing Dpysl2 ORF gene or Dpysl2-siRNA was inserted into recombinant plasmid HIV, then the recombinant of over expression vector was identified by digestion with Xhol and EcoR1, and sequencing of ORF cloning. Pseudovirion containing the recombinants were produced by virus packaging with 293Tα cell, and then the pseudovirion was transfected into HT1299 cell to detect the virus titer.  PC12 were divided into two groups: transfected pseudo virus particles and the control. RT-PCR and WB analysis were performed to observe the changes of Dpysl2 expression after transfection. Results: Successful recombinant vector of over expression and siRNA were identified by digestion with Xhol and EcoR1 and sequencing results. At 48h post-transfection, both of the mRNA and protein level of PC12 were up-regulated in transfected group compared to control group, P<0.05 and P<0.01, respectively. Conclusion: Recombinant vectors of Dpysl2 could effectively regulate the expression of Dpysl2.
Ling Jiang1, Yan Tan2, JieTian1, Hong-Yu Ma2, Jin-Tao Li3*, Chao-Zhi Luo1*
Ibrain 2015;1(1):1-8 Download
Backround: Stroke-associated pneumonia (SAP) is the most common complication after stroke, which increases the long-term mortality. In the acute phase of brain ischemia, obvious pathological injury is observed, which act as a main inducer for SAP. In this study, we sought to investigate the pathological changes following brain ischemia at each pulmonary lobe. Methods: Transient middle cerebral artery occlusion (tMCAO) was applied as a model of cerebral ischemia/reperfusion (I/R) injury (CIRI). Zea-Longa neurological deficit score was assessed at 24h post-injury and TTC staining was used to confirm the successful establishment of model. Histology and lung water content of each pulmonary lobe were conducted to evaluated the degree of lung injury. Results: Anatomy revealed that pulmonary lobes were divided into five single lobes. The posterior lobe of right lung gained the lowest histopathologic score while the highest water content was observed in left single lobe. Conclusions: Therefore, different pulmonary lobes may differ in the degree of lung injury induced by brain ischemia. This provide a novel and rigorous method for the study of lung injury.
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