Electroacupuncture stimulation of the brachial plexus trunk on the healthy side promotes brain-derived neurotrophic factor mRNA expression in the ischemic cerebral cortex of a rat model of cerebral ischemia/reperfusion injury

A rat model of cerebral ischemia/reperfusion was established by suture occlusion of the left middle cerebral artery. In situ hybridization results showed that the number of brain-derived neurotrophic factor mRNA-positive cells in the ischemic rat cerebral cortex increased after cerebral ischemia/ reperfusion injury. Low frequency continuous wave electroacupuncture （frequency 2-6 Hz, current intensity 2 mA） stimulation of the brachial plexus trunk on the healthy （right） side increased the number of brain-derived neurotrophic factor mRNA-positive cells in the ischemic cerebral cortex 14 days after cerebral ischemia/reperfusion injury. At the same time, electroacupuncture stimulation of the healthy brachial plexus truck significantly decreased neurological function scores and alleviated neurological function deficits. These findings suggest that electroacupuncture stimulation of the brachial plexus trunk on the healthy （right） side can greatly increase brain-derived neurotrophic factor mRNA expression and improve neurological function.

Effects of “Nourishing Liver and Kidney” Acupuncture Therapy on Expression of Brain Derived Neurotrophic Factor and Synaptophysin after Cerebral Ischemia Reperfusion in Rats

The aim of the present study was to investigate the effect of ＂nourishing liver and kidney＂ acupuncture therapy on motor and cognitive deficits,and the underlying mechanism following cerebral ischemia-reperfusion（I/R） via increasing the expression of brain derived neurotrophic factor（BDNF） and synaptophysin（SYN） in the hippocampus.Healthy adult male SD rats were randomly divided into sham operation group（n=51）,model group（n=51）,acupuncture group（n=51） and acupuncture control group（n=51）.The middle cerebral I/R model was established.Acupunctures were performed in the acupuncture group and acupuncture control group at acupoints of Taixi（K103）,Taichong（ST09） of both sides,for 30 min once daily every morning.The animals in the sham operation group and model group were conventionally fed in the cage,without any intervention therapy.The rats of each group were assessed with modified neurological severity scores（m NSS）.The expression of BDNF and SYN in the hippocampus was detected by immunohistochemical SP method and the synaptic structure in hippocampus area was assessed morphologically and quantitatively at the 3rd,7th and 14 th day.The Morris water Maze（MWM） test was used to evaluate the rats＇ learning and memory abilities on the 15 th day after acupuncture.The animals in the acupuncture control group and sham operation group presented no neurological deficit.In the acupuncture group,the nerve functional recovery was significantly better than that in the model group at the 7th and 14 th day after modeling.The average MWM escape latency in the acupuncture group was shorter than that in the model group at the 3rd,4th and 5th day.The number of crossings of the platform quadrant in the acupuncture group was significantly more than that in the model group.At the each time point,the expression levels of BDNF and SYN in the hippocampal regions increased significantly in the model group as compared with the sham operation group and the acupuncture control group.In the acupuncture group,the expression levels of BDNF at the 7th and 14 th day increased more significantly than those in the model group.In the acupuncture group,the expression levels of SYN at the each time point increased more significantly than those in the model group.The post-synaptic density（PSD） was significantly increased and the synapse cleft width was narrowed in the acupuncture group as compared with other groups.The synaptic curvatures were improved obviously in the acupuncture group in contrast to the model group.It was concluded that the ＂nourishing liver and kidney＂ acupuncture therapy has positive effects on behavioral recovery,as well as learning and memory abilities,probably by promoting the expression of BDNF and SYN,and synaptic structure reconstruction in the ipsilateral hippocampus after I/R in rats.The ＂nourishing liver and kidney＂ acupuncture therapy can promote the functional recovery in rats after cerebral ischemia injury.

Role of brain-derived neurotrophic factor during the regenerative response after traumatic brain injury in adult zebrafish

Several mammalian animal models of traumatic brain injury have been used, mostly rodents. However, reparative mechanisms in mammalian brain are very limited, and newly formed neurons do not survive for long time. The brain of adult zebrafish, a teleost fish widely used as vertebrate model, possesses high regenerative properties after injury due to the presence of numerous stem cells niches. The ventricular lining of the zebrafish dorsal telencephalon is the most studied neuronal stem cell niche because its dorso-lateral zone is considered the equivalent to the hippocampus of mammals which contains one of the two constitutive neurogenic niches of mammals. To mimic TBI, stab wound in the dorso-lateral telencephalon of zebrafish was used in studies devoted to fish regenerative properties. Brain-derived neurotrophic factor, which is known to play key roles in the repair process after traumatic brain lesions, persists around the lesioned area of injured telencephalon of adult zebrafish. These results are extensively compared to reparative processes in rodent brain. Considering the complete repair of the damaged area in fish, it could be tempting to consider brain-derived neurotrophic factor as a factor contributing to create a permissive environment that enables the establishment of new neuronal population in damaged brain.

Therapeutic potential of brain-derived neurotrophic factor(BDNF)and a small molecular mimics of BDNF for traumatic brain injury

Traumatic brain injury（TBI） is a major health problem worldwide.Following primary mechanical insults,a cascade of secondary injuries often leads to further neural tissue loss.Thus far there is no cure to rescue the damaged neural tissue.Current therapeutic strategies primarily target the secondary injuries focusing on neuroprotection and neuroregeneration.The neurotrophin brain-derived neurotrophic factor（BDNF） has significant effect in both aspects,promoting neuronal survival,synaptic plasticity and neurogenesis.Recently,the flavonoid 7,8-dihydroxyflavone（7,8-DHF）,a small Trk B agonist that mimics BDNF function,has shown similar effects as BDNF in promoting neuronal survival and regeneration following TBI.Compared to BDNF,7,8-DHF has a longer half-life and much smaller molecular size,capable of penetrating the blood-brain barrier,which makes it possible for non-invasive clinical application.In this review,we summarize functions of the BDNF/Trk B signaling pathway and studies examining the potential of BDNF and 7,8-DHF as a therapy for TBI.

Neural stem cells over-expressing brain-derived neurotrophic factor promote neuronal survival and cytoskeletal protein expression in traumatic brain injury sites

Cytoskeletal proteins are involved in neuronal survival.Brain-derived neurotrophic factor can increase expression of cytoskeletal proteins during regeneration after axonal injury.However,the effect of neural stem cells genetically modified by brain-derived neurotrophic factor transplantation on neuronal survival in the injury site still remains unclear.To examine this,we established a rat model of traumatic brain injury by controlled cortical impact.At 72 hours after injury,2 × 10~7 cells/m L neural stem cells overexpressing brain-derived neurotrophic factor or naive neural stem cells（3 m L） were injected into the injured cortex.At 1–3 weeks after transplantation,expression of neurofilament 200,microtubule-associated protein 2,actin,calmodulin,and beta-catenin were remarkably increased in the injury sites.These findings confirm that brain-derived neurotrophic factor-transfected neural stem cells contribute to neuronal survival,growth,and differentiation in the injury sites.The underlying mechanisms may be associated with increased expression of cytoskeletal proteins and the Wnt/β-catenin signaling pathway.

Repair of spinal cord injury by neural stem cells transfected with brain-derived neurotrophic factor-green fluorescent protein in rats A double effect of stem cells and growth factors?

Brain-derived neurotrophic factor（BDNF）can significantly promote nerve regeneration and repair.High expression of the BDNF-green fluorescent protein（GFP）gene persists for a long time after transfection into neural stem cells.Nevertheless,little is known about the biological characteristics of BDNF-GFP modified nerve stem cells in vivo and their ability to induce BDNF expression or repair spinal cord injury.In the present study,we transplanted BDNF-GFP transgenic neural stem cells into a hemisection model of rats.Rats with BDNF-GFP stem cells exhibited significantly increased BDNF expression and better locomotor function compared with stem cells alone.Cellular therapy with BDNF-GFP transgenic stem cells can improve outcomes better than stem cells alone and may have therapeutic potential for spinal cord injury.

Combination of bone marrow mesenchymal stem cells and brain-derived neurotrophic factor for treating spinal cord injury

BACKGROUND： Because bone marrow mesenchymal stem cells （BMSCs） do not secrete sufficient brain-derived neurotrophic factor （BDNF）, the use of exogenous BDNF could improve microenvironments in injured regions for BMSCs differentiation. OBJECTIVE： To analyze recovery of the injured spinal cord following BMSCs venous transplantation in combination with consecutive injections of BDNF. DESIGN, TIME AND SETTING： A randomized, controlled animal experiment was performed at the Central Laboratory of First Hospital and Anatomical Laboratory, Fujian Medical University from October 2004 to May 2006. MATERIALS： Human BDNF was purchased from Sigma, USA. METHODS： A total of 44 New Zealand rabbits were randomly assigned to model （n = 8）, BDNF （n = 12）, BMSC （n= 12）, and BMSC＋BDNF （n= 12） groups. Spinal cord （I-2）injury was established with the dropping method. The model group rabbits were injected with 1 mL normal saline via the ear margin vein; the BDNF group was subdurally injected with 100 μg/d human BDNF for 1 week; the BMSC group was injected with 1 mL BMSCs suspension （2 × 10^6/mL） via the ear margin vein; and the BMSC＋BDNF group rabbits were subdurally injected with 100 μg/d BDNF for 1 week, in addition to BMSCs suspension via the ear margin vein. MAIN OUTCOME MEASURES： BMSCs surface markers were detected by flow cytometry. BMSCs differentiation in the injured spinal cord was detected by immunofluorescence histochemistry. Functional and structural recovery, as well as morphological changes, in the injured spinal cord were respectively detected by Tarlov score, horseradish peroxidase retrograde tracing, and hematoxylin ＆ eosin staining methods at 1, 3, and 5 weeks following transplantation. RESULTS： Transplanted BMSCs differentiated into neuronal-like cells in the injured spinal cord at 3 and 5 weeks following transplantation. Neurological function and pathological damage improved following BMSC ＋ BDNF treatment compared with BDNF or BMSC alone （P 〈 0.01 or P 〈 0.05）. CONCLUSION： BMSCs venous transplantation in combination with BDNF subdural injection benefits neuronal-like cell differentiation and significantly improves structural and function of injured spinal cord compared with BMSCs or BDNF alone.

Adenovirus-mediated human brain-derived neurotrophic factor gene-modified bone marrow mesenchymal stem cell transplantation for spinal cord injury

Rat bone marrow mesenchymal stem cells expressing brain-derived neurotrophic factor were successfully obtained using a gene transfection method, then intravenously transplanted into rats with spinal cord injury. At 1,3, and 5 weeks after transplantation, the expression of brain-derived neurotrophic factor and neurofilament-200 was upregulated in the injured spinal cord, spinal cord injury was alleviated, and Basso-Beattie-Bresnahan scores of hindlimb motor function were significantly increased. This evidence suggested that intravenous transplantation of adenovirus- mediated brain-derived neurotrophic factor gene-modified rat bone marrow mesenchymal stem cells could play a dual role, simultaneously providing neural stem cells and neurotrophic factors.

Agmatine promotes expression of brain-derived neurotrophic factor in brainstem facial nucleus in the rat facial nerve injury model

BACKGROUND： Studies have shown that agmatine can reduce inhibition of neuronal regeneration by increasing cyclic adenosine monophosphate and brain-derived neurotrophic factor （BDNF） in the hippocampus of morphine-dependent rats. The hypothesis that agmatine exerts similar effects on facial nerve injury deserves further analysis. OBJECTIVE： To study the effects of peritoneal agmatine injection on BDNF levels in the rat brainstem after facial nerve injury. DESIGN, TIME AND SETTING： A controlled animal experiment was performed at the Department of Otolaryngology-Head and Neck Surgery at the Second Affiliated Hospital, Chongqing University of Medical Sciences （Chongqing, China）, between October and December in 2007. MATERIALS： Twenty-four male Sprague-Dawley rats were randomly divided into a control, a lesion, and an agmatine treatment group, with eight rats in each group. Bilateral facial nerve anastomosis was induced in the lesion and agmatine treatment groups, while the control group remained untreated. A rat BDNF Enzyme-linked immunosorbent assay kit was used to measure BDNF levels in the brainstem facial nucleus. METHODS： Starting on the day of lesion, the agmatine group received a peritoneal injection of 100 mg/kg agmatine, once per day, for a week, whereas rats in the lesion group received saline injections. MAIN OUTCOME MEASURES： BDNF levels in the brainstem containing facial nucleus were measured by ELISA. RESULTS： Twenty-four rats were included in the final analysis without any loss. Two weeks after lesion, BDNF levels were significantly higher in the lesion group than in the control group （P 〈 0.01）. A significant increase was noted in the agmatine group compared to the lesion group （P 〈 0.01）. CONCLUSION： Agmatine can substantially increase BDNF levels in the rat brainstem after facial nerve injury.

Neuronal injury and brain-derived neurotrophic factor expression in a rat model of amygdala kindling seizures Differences in brain regions and kindling courses

BACKGROUND：Studies have demonstrated that brain-derived neurotrophic factor （BDNF） has a dual effect on epilepsy. However, the relationship between epilepsy-induced brain injury and BDNF remains poorly understood.OBJECTIVE：According to ultrastructural and molecular parameters, to detect the degree of neuronal injury and BDNF expression changes at different brain regions and different kindling times to determine the effects of BDNF on epilepsy-induced brain injury.DESIGN, TIME AND SETTING：A randomized, controlled, animal experiment based on neuropathology and molecular biology was performed at the Department of Physiology and Department of Pathology, Basic Medical College of Jilin University in 2003.MATERIALS：UltraSensitiveTM SP kit for immunohistochemistry （Fuzhou Maxim Biotechnology, China）, BDNF antibody （concentrated type, Wuhan Boster Biological Technology, China）, JEM-1000SX transmission electron microscopy （JEOL, Japan）, and BH-2 light microscope （Olympus, Japan） were used in the present study.METHODS：Wistar rats were randomly assigned to control （n = 6）, sham-surgery （n = 6）, and model （n = 60） groups. The control group rats were not treated; an electrode was embedded into the amygdala in rats from the sham-surgery and model groups; an amygdala kindling epilepsy model was established in the model group.MAIN OUTCOME MEASURES：Pathological changes in the temporal lobe and hippocampus were observed by light and electron microscopy at 1, 3, 7, 14, and 21 days following kindling, and BDNF expression in the various brain regions was determined by immunohistochemistry.RESULTS：In the model group, temporal lobe cortical and hippocampal neurons were swollen and the nuclei were laterally deviated. There were also some apoptotic neurons 3 days after kindling. The nucleoli disappeared and the nuclei appeared broken or lysed, as well as slight microglia hyperplasia, at 7 days. Electron microscopic observation displayed chromatin aggregation in the nuclei and slight mitochondrion swelling 3 days after kindling. Injury changes were aggravated at 7 days, characterized by broken cytoplasmic membrane and pyknosis. With the development of seizure, the number of BDNF-positive neurons in the hippocampus and temporal lobe increased and peaked at 7 days. Moreover, hippocampal and cortical temporal lobe injury continued. Following termination of electrical stimulation after 7 days of kindling, BDNF expression decreased, but continued to be expressed, up to 21 days of kindling. In addition, the number of temporal and hippocampal BDNF-positive neurons was greater than the control group.CONCLUSION：Brain injury and BDNF expression peaked at 7 days after kindling, and hippocampal changes were significant.

Brain-derived neurotrophic factor gene transfection promotes neuronal repair and neurite regeneration after diffuse axonal injury

This study sought to assess the potential of brain-derived neurotrophic factor （BDNF） to promote neuronal repair and regeneration in rats with diffuse axonal injury, and to examine the accompanying neurobiological changes. BDNF gene transfection reduced the severity of the pathological changes associated with diffuse axonal injury in cortical neurons of the frontal lobe and increased neurofilament protein expression. These findings demonstrate that BDNF can effectively promote neuronal repair and neurite regeneration after diffuse axonal injury.

Correlation of brain-derived neurotrophic factor to cognitive impairment following traumatic brain injury in rats

BACKGROUND： In vitro and in vivo studies have confirmed that brain-derived neurotrophic factor （BDNF） can promote survival and differentiation of cholinergic, dopaminergic and motor neurons, and axonal regeneration. BDNF has neuroprotective effects on the nervous system. OBJECTIVE： To explore changes in BDNF expression and cognitive function in rats after brain injury. DESIGN, TIME AND SETTING： The neuropathology experiment was performed at the Second Research Room, Department of Neurosurgery, Fujian Medical University （China） from July 2007 to July 2008. MATERIALS： A total of 72 healthy, male, Sprague Dawley, rats were selected for this study. METHODS： Rat models of mild and moderate traumatic brain injury were created by percussion, according to Feeney＇s method （n = 24, each group）. A bone window was made in rats from the sham operation group （n = 24）, but no attack was conducted. MAIN OUTCOME MEASURES： At days 1, 2, 4 and 7 following injury, BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain was examined by immunohistochemistry （streptavidin-biotin-peroxidase complex method）. Changes in rat cognitive function were assessed by the walking test, balance-beam test and memory function detection. RESULTS： Cognitive impairment was aggravated at day 2, and recovered to normal at days 3 and 7 in rats from the mild and moderate traumatic brain injury groups. BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain was increased at 1 day, decreased at day 2, and then gradually increased in the mild and moderate traumatic brain injury groups. BDNF expression was greater in rats from the moderate traumatic brain injury group than in the sham operation and mild traumatic brain injury groups （P 〈 0.05）. CONCLUSION： BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain is correlated to cognitive impairment after traumatic brain injury. BDNF has a protective effect on cognitive function in rats following injury.

Interventional effect of laser acupoint radiation on the expression of Nissl body and brain-derived neurotrophic factor in newborn rat models with ischemic/hypoxic cerebral injury

BACKGROUND： Some researches report that He-Ne laser can activate function of erythrocytes and increase content of blood and oxygen via bio-stimulating effect; therefore, it suspects that laser radiation at Baihui and Dazhui can partially increase blood circulation for oxygen-supplying content of brain and improve functional status of neurons. OBJECTIVE： To verify the effects of laser radiation at Baihui and Dazhui on the expression of Nissl body of brain tissue neurons and brain-derived neurotrophic factor （BDNF） in newborn rats with ischemic/hypoxic cerebral injury. DESIGN： Randomized controlled animal study. SETTING： Department of Neurological Histochemistry, Xianning University. MATERIALS： Forty Wistar rats of 7 - 8 days old, weighing 15 - 20 g and of both genders, were selected from Wuhan Experimental Animal Center. All the rats were randomly divided into sham operation group （n =8）, model group （n =16） and radiation group （n = 16）. The experimental animals were disposed according to ethical criteria. BDNF kit was provided by Wuhan Boster Bioengineering Co., Ltd. METHODS： The experiment was carried out in the Department of Neurological Histochemistry, Xianning University from April 2005 to October 2006. Rats in the radiation group and model group were performed with ligation of left common carotid artery, recovered at room temperature for 1 - 6 days, maintained in self-made hypoxic cabin under normal pressure and injected mixture gas （0.05 volume fraction of 02 and 0.92 volume fraction of N2） for 2 hours. In addition, rats in the sham operation group were treated with separation of left common carotid artery but not ligation and hypoxia. Rats in the model group were not given any treatment; while, rats in the radiation group were exposed with He-Ne laser of 63.28 nm in the wave length at Baihui and Dazhui acupoints on the second day after ischemia-hypoxia. The radiation was given for 10 minutes per day and once a day. Ten days were regarded as a course and the rats were exposed for 2 courses in total. At 20 days after routine breeding, left hemisphere tissues of rats in the three groups were collected for staining of Nissl body and immunohistochemistry of BDNF. MAIN OUTCOME MEASURES： Nissl body staining in left hemisphere tissue and expression of immune positive cells of BDNF. RESULTS： All 40 rats were involved in the final analysis. （1） Nissl body staining： Neuronal cytoplasm of brain tissue was full of blue granule Nissl bodies in the sham operation group; while, Nissl body in neuronal cytoplasm in the model group was stained slightly and had a certain degree of degeneration; meanwhile, there were a lot of blank area in ischemic region. Nissl body in neuron cytoplasm was gradually recovered in the radiation group and relieved as compared with that in the model group. （2） Positive cells of BDNF： Number of immune positive cells of BDNF which were ligated in lateral cerebral hemisphere of rats in the model group was higher than that in the sham operation group （P 〈 0.05）; while, BDNF expression in the radiation group was increased as compared with that in the model group （P 〈 0.05）. CONCLUSION： After laser acupoint radiation, Nissl body is increased and BDNF expression is also increased. This suggests that laser acupoint radiation has neuroprotective effect on brain tissue after ischemia-hypoxia injury.

Brain-derived neurotrophic factor inhibits glucose intolerance after cerebral ischemia

Brain-derived neurotrophic factor is associated with the insulin signaling pathway and glucose me- tabolism. We hypothesized that expression of brain-derived neurotrophic factor and its receptor may be involved in glucose intolerance following ischemic stress. To verify this hypothesis, this study aimed to observe the changes in brain-derived neurotrophic factor and tyrosine kinase B receptor expression in glucose metabolism-associated regions following cerebral ischemic stress in mice. At day 1 after middle cerebral artery occlusion, the expression levels of brain-derived neurotrophic factor were significantly decreased in the ischemic cortex, hypothalamus, liver, skeletal muscle, and pancreas. The expression levels of tyrosine kinase B receptor were decreased in the hypothalamus and liver, and increased in the skeletal muscle and pancreas, but remained unchanged in the cortex Intrahypothalamic administration of brain-derived neurotrophic factor （40 ng） suppressed the de- crease in insulin receptor and tyrosine-phosphorylated insulin receptor expression in the liver and skeletal muscle, and inhibited the overexpression of gluconeogenesis-associated phosphoenolpy- ruvate carboxykinase and glucose-6-phosphatase in the liver of cerebral ischemic mice. However, serum insulin levels remained unchanged. Our experimental findings indicate that brain-derived neurotrophic factor can promote glucose metabolism, reduce gluconeogenesis, and decrease blood glucose levels after cerebral ischemic stress. The low expression of brain-derived neurotrophic factor following cerebral ischemia may be involved in the development of glucose intolerance.

Brain-derived neurotrophic factor mediates macrophage migration inhibitory factor to protect neurons against oxygen-glucose deprivation

Macrophage migration inhibitory factor(MIF)is a chemokine that plays an essential role in immune system function.Previous studies suggested that MIF protects neurons in ischemic conditions.However,few studies are reported on the role of MIF in neurological recovery after ischemic stroke.The purpose of this study is to identify the molecular mechanism of neuroprotection mediated by MIF.Human neuroblastoma cells were incubated in Dulbecco’s modified Eagle’s medium under oxygen-glucose deprivation(OGD)for 4 hours and then returned to normal aerobic environment for reperfusion(OGD/R).30 ng/mL MIF recombinant(30 ng/mL)or ISO-1(MIF antagonist;50μM)was administered to human neuroblastoma cells.Then cell cultures were assigned to one of four groups:control,OGD/R,OGD/R with MIF,OGD/R with ISO-1.Cell viability was analyzed using WST-1 assay.Expression levels of brain-derived neurotrophic factor(BDNF),microtubule-associated protein 2(MAP2),Caspase-3,Bcl2,and Bax were detected by western blot assay and immunocytochemistry in each group to measure apoptotic activity.WST-1 assay results revealed that compared to the OGD/R group,cell survival rate was significantly higher in the OGD/R with MIF group and lower in the OGD/R with ISO-1 group.Western blot assay and immunocytochemistry results revealed that expression levels of BDNF,Bcl2,and MAP2 were significantly higher,and expression levels of Caspase-3 and Bax were significantly lower in the MIF group than in the OGD/R group.Expression levels of BDNF,Bcl2,and MAP2 were significantly lower,and expression levels of Caspase-3 and Bax were significantly higher in the ISO-1 group than in the OGD/R group.MIF administration promoted neuronal cell survival and induced high expression levels of BDNF,MAP2,and Bcl2(anti-apoptosis)and low expression levels of Caspase-3 and Bax(pro-apoptosis)in an OGD/R model.These results suggest that MIF administration is effective for inducing expression of BDNF and leads to neuroprotection of neuronal cells against hypoxic injury.

Electroacupuncture promotes peripheral nerve regeneration after facial nerve crush injury and upregulates the expression of glial cell-derived neurotrophic factor

The efficacy of electroacupuncture in the treatment of peripheral facial paralysis is known, but the specific mechanism has not been clarified. Glial cell-derived neurotrophic factor(GDNF) has been shown to protect neurons by binding to N-cadherin. Our previous results have shown that electroacupuncture could increase the expression of N-cadherin mRNA in facial neurons and promote facial nerve regeneration. In this study, the potential mechanisms by which electroacupuncture promotes nerve regeneration were elucidated through assessing the effects of electroacupuncture on GDNF and N-cadherin expression in facial motoneurons of rabbits with peripheral facial nerve crush injury. New Zealand rabbits were randomly divided into a normal group(normal control, n = 21), injury group(n = 45) and electroacupuncture group(n = 45). Model rabbits underwent facial nerve crush injury only. Rabbits in the electroacupuncture group received facial nerve injury, and then underwent electroacupuncture at Yifeng(TE17), Jiache(ST6), Sibai(ST2), Dicang(ST4), Yangbai(GB14), Quanliao(SI18), and Hegu(LI4; only acupuncture, no electrical stimulation). The results showed that in behavioral assessments, the total scores of blink reflex, vibrissae movement, and position of apex nasi, were markedly lower in the EA group than those in the injury group. Hematoxylin-eosin staining of the right buccinator muscle of each group showed that the cross-sectional area of buccinator was larger in the electroacupuncture group than in the injury group on days 1, 14 and 21 post-surgery. Toluidine blue staining of the right facial nerve tissue of each group revealed that on day 14 post-surgery, there was less axonal demyelination and fewer inflammatory cells in the electroacupuncture group compared with the injury group. Quantitative real time-polymerase chain reaction showed that compared with the injury group, N-cadherin mRNA levels on days 4, 7, 14 and 21 and GDNF mRNA levels on days 4, 7 and 14 were significantly higher in the electroacupuncture group. Western blot assay displayed that compared with the injury group, the expression of GDNF protein levels on days 7, 14 and 21 were significantly upregulated in the electroacupuncture group. The histology with hematoxylin-eosin staining and Nissl staining of brainstem tissues containing facial neurons in the middle and lower part of the pons exhibited that on day 7 post-surgery, there were significantly fewer apoptotic neurons in the electroacupuncture group than in the injury group. By day 21, there was no significantly difference in the number of neurons between the electroacupuncture and normal groups. Taken together, these results have confirmed that electroacupuncture promotes regeneration of peripheral facial nerve injury in rabbits, inhibits neuronal apoptosis, and reduces peripheral inflammatory response, resulting in the recovery of facial muscle function. This is achieved by up-regulating the expression of GDNF and N-cadherin in central facial neurons.

Gastrodin promotes the secretion of brain-derived neurotrophic factor in the injured spinal cord

Gastrodin, an active component of tall gastrodia tuber, is widely used in the treatment of dizziness, paralysis, epilepsy, stroke and dementia, and exhibits a neuroprotective effect. A rat model of spinal cord injury was established using Allen＇s method, and gastrodin was administered via the subarachnoid cavity and by intraperitoneal injection for 7 days. Results show that gastrodin promoted the secretion of brain-derived neurotrophic factor in rats with spinal cord injury. After gastrodin treatment, the maximum angle of the inclined plane test, and the Basso, Beattie and Bresnahan scores increased. Moreover, gastrodin improved neural tissue recovery in the injured spinal cord. These results demonstrate that gastrodin promotes the secretion of brain-derived neurotrophic factor, contributes to the recovery of neurological function, and protects neural cells against injury.

Intraspinal transplantation of motoneuron-like cell combined with delivery of polymer-based glial cell line-derived neurotrophic factor for repair of spinal cord contusion injury

To evaluate the effects of glial cell line-derived neurotrophic factor transplantation combined with adipose-derived stem cells-transdifferentiated motoneuron delivery on spinal cord con-tusion injury, we developed rat models of spinal cord contusion injury, 7 days later, injected adipose-derived stem cells-transdifferentiated motoneurons into the epicenter, rostral and caudal regions of the impact site and simultaneously transplanted glial cell line-derived neuro-trophic factor-gelfoam complex into the myelin sheath. Motoneuron-like cell transplantation combined with glial cell line-derived neurotrophic factor delivery reduced cavity formations and increased cell density in the transplantation site. The combined therapy exhibited superior promoting effects on recovery of motor function to transplantation of glial cell line-derived neurotrophic factor, adipose-derived stem cells or motoneurons alone. These ifndings suggest that motoneuron-like cell transplantation combined with glial cell line-derived neurotrophic factor delivery holds a great promise for repair of spinal cord injury.

Overexpression of brain-derived neurotrophic factor in the hippocampus protects against post-stroke depression

Post-stroke depression is associated with reduced expression of brain-derived neurotrophic factor （BDNF）. In this study, we evaluated whether BDNF overexpression affects depression-like behavior in a rat model of post-stroke depression. The middle cerebral artery was occluded to produce a model of focal cerebral ischemia. These rats were then subjected to isolation-housing combined with chronic unpredictable mild stress to generate a model of post-stroke depression. A BDNF gene lentiviral vector was injected into the hippocampus. At 7 days after injection, western blot assay and real-time quantitative PCR revealed that BDNF expression in the hippo- campus was increased in depressive rats injected with BDNF lentivirus compared with depressive rats injected with control vector. Furthermore, sucrose solution consumption was higher, and horizontal and vertical movement scores were increased in the open field test in these rats as well. These findings suggest that BDNF overexpression in the hippocampus of post-stroke depressive rats alleviates depression-like behaviors.

Combining acellular nerve allografts with brainderived neurotrophic factor transfected bone marrow mesenchymal stem cells restores sciatic nerve injury better than either intervention alone

In this study, we chemically extracted acellular nerve allografts from bilateral sciatic nerves, and repaired 10-mm sciatic nerve defects in rats using these grafts and brain-derived neurotrophic factor transfected bone marrow mesenchymal stem cells. Experiments were performed in three groups： the acellular nerve allograft bridging group, acellular nerve allograft ＋ bone marrow mesenchymal stem cells group, and the acellular nerve allograft ＋ brain-derived neurotrophic factor transfected bone marrow mesenchyrnal stem cells group. Results showed that at 8 weeks after bridging, sciatic functional index, triceps wet weight recovery rate, myelin thickness, and number of myelinated nerve fibers were significantly changed in the three groups. Variations were the largest in the acellular nerve allograft ＋ brain-derived neurotrophic factor transfected bone marrow mesenchymal stem cells group compared with the other two groups. Experimental findings suggest that chemically extracted acellular nerve allograft combined nerve factor and mesenchymal stem cells can promote the restoration of sciatic nerve defects. The repair effect seen is better than the single application of acellular nerve allograft or acellular nerve allograft combined mesenchymal stem cell transplantation.