Spinal cord injury drives chronic brain changes

Only a few studies have considered changes in brain structures other than sensory and motor cortex after spinal cord injury,although cognitive impairments have been reported in these patients.Spinal cord injury results in chronic brain neuroinflammation with consequent neurodegeneration and cognitive decline in rodents.Regarding the hippocampus,neurogenesis is reduced and reactive gliosis increased.These longterm abnormalities could explain behavioral impairments exhibited in humans patients suffering from spinal cord trauma.

Non-invasive brain stimulation to promote motor and functional recovery following spinal cord injury

We conducted a systematic review of studies using non-invasive brain stimulation（NIBS： repetitive transcranial magnetic stimulation（r TMS） and transcranial direct current stimulation（t DCS）） as a research and clinical tool aimed at improving motor and functional recovery or spasticity in patients following spinal cord injury（SCI） under the assumption that if the residual corticospinal circuits could be stimulated appropriately, the changes might be accompanied by functional recovery or an improvement in spasticity. This review summarizes the literature on the changes induced by NIBS in the motor and functional recovery and spasticity control of the upper and lower extremities following SCI.

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.

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.

Effects of brain-derived neurotrophic factor on synapsin expression in rat spinal cord anterior horn neurons cultured in vitro

Brain-derived neurotrophic factor （BDNF） promotes synaptic formation and functional maturation by upregulating synapsin expression in cortical and hippocampal neurons. However, it remains controversial whether BDNF affects synapsin expression in spinal cord anterior horn neurons. Wistar rat spinal cord anterior horn neurons were cultured in serum-supplemented medium containing BDNF, BDNF antibody, and Hank＇s solution for 3 days, and then synapsin I and synaptophysin protein and mRNA expression was detected. Under serum-supplemented conditions the number of surviving neurons in the spinal cord anterior horn was similar among BDNF, anti-BDNF, and control groups （P 〉 0.05）. Synapsin I and synaptophysin protein and mRNA expressions were increased in BDNF-treated neurons, but decreased in BDNF antibody-treated neurons （P 〈 0.01）. These results indicated that BDNF significantly promotes synapsin I and synaptophysin expression in in vitro-cultured rat spinal cord anterior horn neurons.

Transactivating-transduction protein-polyethylene glycol modified liposomes traverse the blood-spinal cord and blood-brain barriers

Naive liposomes can cross the blood-brain barrier and blood-spinal cord barrier in small amounts. Liposomes modified by a transactivating-transduction protein can deliver antibiotics for the treatment of acute bacterial infection-induced brain inflammation. Liposomes conjugated with polyethylene glycol have the capability of long-term circulation. In this study we prepared transactivating-transduction protein-polyethylene glycol-modified liposomes labeled with fiuorescein isothiocyanate. Thus, liposomes were characterized by transmembrane, long-term circulation and fluorescence tracing. Uptake, cytotoxicity, and the ability of traversing blood-spinal cord and blood-brain barriers were observed following coculture with human breast adenocarcinoma cells （MCF-7）. Results demonstrated that the liposomes had good biocompatibility, and low cytotoxicity when cocultured with human breast adenocarcinoma cells. Liposomes could traverse cell membranes and entered the central nervous system and neurocytes through the blood-spinal cord and blood-brain barriers of rats via the systemic circulation. These results verified that fluorescein isothiocyanate-modified transactivating-transduction protein-polyethylene glycol liposomes have the ability to traverse the blood-spinal cord and blood-brain barriers.

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.

Intranasal nerve growth factor bypasses the blood-brain barrier and affects spinal cord neurons in spinal cord injury

The purpose of this work was to investigate whether, by intranasal administration, the nerve growth factor bypasses the blood-brain barrier and turns over the spinal cord neurons and if such therapeutic approach could be of value in the treatment of spinal cord injury. Adult Sprague-Dawley rats with intact and injured spinal cord received daily intranasal nerve growth factor administration in both nostrils for 1 day or for 3 consecutive weeks. We found an in-creased content of nerve growth factor and enhanced expression of nerve growth factor receptor in the spinal cord 24 hours after a single intranasal administration of nerve growth factor in healthy rats, while daily treatment for 3 weeks in a model of spinal cord injury improved the deifcits in locomotor behaviour and increased spinal content of both nerve growth factor and nerve growth factor receptors. These outcomes suggest that the intranasal nerve growth factor bypasses blood-brain barrier and affects spinal cord neurons in spinal cord injury. They also suggest exploiting the possible therapeutic role of intranasally delivered nerve growth factor for the neuroprotection of damaged spinal nerve cells.

Brain-derived neurotrophic factor and neural plasticity in a rat model of spinal cord transection

The present study employed a rat model of T10 spinal cord transection. Western blot analyses revealed increased brain-dedved neurotrophic factor （BDNF） expression in spinal cord segments caudal to the transection site following injection of replication incompetent herpes simplex virus vector （HSV-BDNF） into the subarachnoid space. In addition, hindlimb locomotor functions were improved. In contrast, BDNF levels decreased following treatment with replication defective herpes simplex virus vector construct small interference BDNF （HSV-siBDNF）. Moreover, hindlimb locomotor functions gradually worsened. Compared with the replication incompetent herpes simplex virus vector control group, extracellular signal regulated kinasel/2 expression increased in the HSV-BDNF group on days 14 and 28 after spinal cord transection, but expression was reduced in the HSV-siBDNF group. These results suggested that BDNF plays an important role in neural plasticity via extracellular signal regulated kinasel/2 signaling pathway in a rat model of adult spina cord transection.

Strategies to avoid a missed diagnosis of co-occurring concussion in post-acute patients having a spinal cord injury

Research scientists and clinicians should be aware that missed diagnoses of mild-moderate traumatic brain injuries in post-acute patients having spinal cord injuries may approach 60-74% with certain risk factors, potentially causing clinical consequences for patients, and confounding the results of clinical research studies. Factors leading to a missed diagnosis may include acute trauma-related life-threatening issues, sedation/intubation, subtle neuropathology on neuroimaging, failure to collect Glasgow Coma Scale scores or duration of posttraumatic amnesia, or lack of validity of this information, and overlap in neuro-cognitive symptoms with emotional responses to spinal cord injuries. Strategies for avoiding a missed diagnosis of mild-moderate traumatic brain injuries in patients having a spinal cord injuries are highlighted in this perspective.

ABC efflux transporters at blood-central nervous system barriers and their implications for treating spinal cord disorders

The barriers present in the interfaces between the blood and the central nervous system form a major hurdle for the pharmacological treatment of central nervous system injuries and diseases.The family of ATP-binding cassette(ABC)transporters has been widely studied regarding efflux of medications at blood-central nervous system barriers.These efflux transporters include P-glycoprotein(abcb1),‘breast cancer resistance protein'(abcg2)and the various‘multidrug resistance-associated proteins'(abccs).Understanding which efflux transporters are present at the blood-spinal cord,blood-cerebrospinal fluid and cerebrospinal fluid-spinal cord barriers is necessary to determine their involvement in limiting drug transfer from blood to the spinal cord tissue.Recent developments in the blood-brain barrier field have shown that barrier systems are dynamic and the profile of barrier defenses can alter due to conditions such as age,disease and environmental challenge.This means that a true understanding of ABC efflux transporter expression and localization should not be one static value but instead a range that represents the complex patient subpopulations that exist.In the present review,the blood-central nervous system barrier literature is discussed with a focus on the impact of ABC efflux transporters on:(i)protecting the spinal cord from adverse effects of systemically directed drugs,and(ii)limiting centrally directed drugs from accessing their active sites within the spinal cord.

Prevention against diffuse spinal cord astrocytoma: can the Notch pathway be a novel treatment target?

This study was designed to investigate whether the Notch pathway is involved in the develop-ment of diffuse spinal cord astrocytomas. BALB/c nude mice received injections of CD133＋and CD133？ cell suspensions prepared using human recurrent diffuse spinal cord astrocytoma tissue through administration into the right parietal lobe. After 7–11 weeks, magnetic resonance imaging was performed weekly. Xenografts were observed on the surfaces of the brains of mice receiving the CD133＋ cell suspension, and Notch-immunopositive expression was observed in the xenografts. By contrast, no xenografts appeared in the identical position on the surfaces of the brains of mice receiving the CD133？ cell suspension, and Notch-immunopositive expres-sion was hardly detected either. Hematoxylin-eosin staining and immunohistochemical staining revealed xenografts on the convex surfaces of the brains of mice that underwent CD133＋ astro-cytoma transplantation. Some sporadic astroglioma cells showed pseudopodium-like structures, which extended into the cerebral white matter. However,it should be emphasized that the sub-cortex xenograft with Notch-immunopositive expression was found in the fourth mouse received injection of CD133？ astrocytoma cells. However, these ifndings suggest that the Notch pathway plays an important role in the formation of astrocytomas, and can be considered a novel treat-ment target for diffuse spinal cord astrocytoma.

15 Years of Evolution of Non-Invasive EEG-Based Methods for Restoring Hand &Arm Function with Motor Neuroprosthetics in Individuals with High Spinal Cord Injury: A Review of Graz BCI Research

Patients who suffer from a high spinal cord injury have severe motor disabilities in the lower as well as in the upper extremities. Thus they rely on the help of other people in everyday life. Restoring the function of the upper limbs, especially the grasp function can help them to gain some independence. Using EEG-based neuroprosthetics is a way to help tetraplegic people restore different grasp types as well as moving the arm and the elbow. In this work an overview of non-invasive EEG-based methods for restoring the hand and arm function with the use of neuroprosthetics in individuals with high spinal cord injury is given. Since the Graz BCI group is leading in this area of non-invasive research mainly, the work of this group is represented.

Huangqin flavonoid extraction for spinal cord injury in a rat model

Flavonoids from Huangqin（dried roots of Scutellaria baicalensis Georgi） have anti-inflammatory effects, and are considered useful for treatment of spinal cord injury. To verify this hypothesis, the T9-10 spinal cord segments of rats were damaged using Allen＇s method to establish a rat spinal cord injury model. Before model establishment, Huangqin flavonoid extraction（12.5 g/kg） was administered intragastrically for 1 week until 28 days after model establishment. Methylprednisolone（30 mg/kg） was injected into the tail vein at 30 minutes after model establishment as a positive control. Basso, Beattie, and Bresnahan locomotor scale scores were used to assess hind limb motor function. Hematoxylin-eosin staining was used to detect pathological changes in the injured spinal cord. Immunofluorescence and western blot assays were performed to measure immunoreactivity and expression levels of brain-derived neurotrophic factor, neuronal marker neurofilament protein, microglial marker CD11 b and astrocyte marker glial fibrillary acidic protein in the injured spinal cord. Huangqin flavonoid extraction markedly reduced spinal cord hematoma, inflammatory cell infiltration and cavities and scars, and increased the Basso, Beattie, and Bresnahan locomotor scale scores; these effects were identical to those of methylprednisolone. Huangqin flavonoid extraction also increased immunoreactivity and expression levels of brain-derived neurotrophic factor and neurofilament protein, and reduced immunoreactivity and expression levels of CD11 b and glial fibrillary acidic protein, in the injured spinal cord. Overall, these data suggest that Huangqin flavonoid extraction can promote recovery of spinal cord injury by inducing brain-derived neurotrophic factor and neurofilament protein expression, reducing microglia activation and regulating reactive astrocytes.

Functional recovery and microenvironmental alterations in a rat model of spinal cord injury following human umbilical cord blood-derived mesenchymal stem cells transplantation

BACKGROUND： Transplantation of human umbilical cord blood-derived mesenchymal stem cells （MSCs） has been shown to benefit spinal cord injury （SCI） repair. However, mechanisms of microenvironmental regulation during differentiation of transplanted MSCs remain poorly understood. OBJECTIVE： To observe changes in nerve growth factor （NGF）, brain-derived neurotrophic factor （BDNF）, and interleukin-8 （IL-8） expression following transplantation of human umbilical cord-derived MSCs, and to explore the association between microenvironment and neural functional recovery following MSCs transplantation. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Department of Orthopedics, First Affiliated Hospital of Soochow University from April 2005 to March 2007. MATERIALS： Human cord blood samples were provided by the Department of Gynecology and Obstetrics, First Affiliated Hospital of Soochow University. Written informed consent was obtained. METHODS： A total of 62 Wister rats were randomly assigned to control （n = 18）, model （n = 22, SCI ＋ PBS）, and transplantation （n = 22, SCI ＋ MSCs） groups. The rat SCI model was established using the weight compression method. MSCs were isolated from human umbilical cord blood and cultured in vitro for several passages. 5-bromodeoxyuridine （BrdU）-Iabeled MSCs （24 hours before injection） were intravascularly transplanted. MAIN OUTCOME MEASURES： The rats were evaluated using the Basso, Beattie and Bresnahan （BBB） locomotor score and inclined plane tests. Transplanted cells were analyzed following immunohistochemistry. Enzyme-linked immunosorbant assay was performed to determine NGF, BDNF, and IL-8 levels prior to and after cell transplantation. RESULTS： A large number of BrdU-positive MSCs were observed in the SCI region of the transplantation group, and MSCs were evenly distributed in injured spinal cord tissue 1 week after transplantation. BBB score and inclined plane test results revealed significant functional improvement in the transplantation group compared to the model group （P 〈 0.05）, which was maintained for 2-3 weeks. Compared to the model group, NGF and BDNF levels were significantly increased in the injured region following MSCs transplantation at 3 weeks （P 〈 0.05）, but IL-8 levels remained unchanged （P 〉 0.05）. CONCLUSION： MSCs transplantation increased NGF and BDNF expression in injured spinal cord tissue. MSCs could promote neurological function recovery in SCI rats by upregulating NGF expression and improving regional microenvironments.

Protective effect of adenovirus-mediated BDNF gene expression on spinal axon following in rats after spinal cord injury

Objective: To investigate the effects of exogenous brain derived neurotrophic factor(BDNF) expression on in- jured spinal cord by being injected into the cord following its reconstruction with adenovirus. Method: A reliable rat model with injury of different gradation was established by using a weight-drop apparatus with a laser compression recorder. The replicate-defect recombinant adenoviral vector containing BDNF gene was transferred into the site of injured spinal cord by direct injection. The validity of gene transfer was verified with X-Gal staining. The morphological changes of the injured ax- on were studied quantitatively. The expression of BDNF mRNA, and immunocytochemical reactivity of BDNF and neurofila- ment(NF) in injured cord of rats were observed. Results: It was verified that the spinal coal could be effectively infected by injecting the adenoviral vector into the injured cord, and the reporter gene was expressed. The loss of axons reduced following the in vivo infection of adenoviral vector carrying exogenous BDNF gene after in injury, while more NF immunopositive ax- ons than that of normal spical cord were found. Conclusion: With in vivo transfer of adenovirus vector into the injured site, a certain extent of protection could be provided to the injured axons by increasing local expressions of exogenous DBNF, and renovation of the cytoskeleton in the injured neurons was facilitated. These double effects are both important in gene therapy of spinal cord injuries.

Panax notoginseng saponins improve recovery after spinal cord transection by upregulating neurotrophic factors

Saponins extracted from Panax notoginseng are neuroprotective, but the mechanisms underlying this effect remain unclear. In the present study, we established a rat model of thoracic（T10） spinal cord transection, and injected Panax notoginseng saponins（100 mg/kg） or saline 30 minutes after injury. Locomotor functions were assessed using the Basso, Beattie, and Bresnahan（BBB） scale from 1 to 30 days after injury, and immunohistochemistry was carried out in the ventral horn of the spinal cord at 1 and 7 days to determine expression of nerve growth factor（NGF） and brain-derived neurotrophic factor（BDNF）. Our results show that at 7–30 days post injury, the BBB score was higher in rats treated with Panax notoginseng saponins than in those that received saline. Furthermore, at 7 days, more NGF- and BDNF-immunoreactive neurons were observed in the ventral horn of the spinal cord of rats that had received Panax notoginseng saponins than in those that received saline. These results indicate that Panax notoginseng saponins caused an upregulation of NGF and BDNF in rats with spinal cord transection, and improved hindlimb motor function.

Intramedullary Spinal Cord Metastases in Breast Cancer: Report a Case

Background: Intramedullary spinal cord metastasis (ISCM) from breast cancer is a relatively rare disease. We present this disease. Case presentation: The patient was a 67-year-old woman with lung metastasis appearing 3 years after breast cancer surgery. Complete remission was achieved for the metastatic lesion with chemotherapy, but multiple cerebellar metastases were found 3 months after the completion of chemotherapy. Whole-brain irradiation was administered, resulting in symptomatic improvement. Approximately 6 months later, the patient experienced weakness in the lower extremities and difficulty walking. Magnetic resonance imaging detected a well-defined intraspinal tumor measuring 13 × 13 × 30 mm at the level of Th12-L1. After 20-Gy irradiation to the tumor, oral steroid administration, and rehabilitation, the patient regained the ability to walk. Eight months have passed, to date, since these interventions and the patient is currently receiving treatment for metastases to bones, including the spine, but is still capable of walking without difficulty. We herein report this case with a review of the relevant literature. Conclusion: ISCM in the breast cancer is relatively rare. But, it is the clinical condition which it should always place in the mind.

载药外泌体在中枢神经系统疾病中的热点问题

背景:利用外泌体作为药物载体不仅可以精确靶向治疗部位,还能提高局部浓度,为药物进入中枢神经系统开辟了一条新途径。目的:探讨外泌体的生物发生、生物学功能,综述当前有关细胞外囊泡作为药物载体在中枢神经系统疾病治疗中的最新进展。方法:由第一作者检索Web of Science、Pub Med和中国知网数据库1976年1月至2024年1月发表的相关文献,以“exosomes,extracellular vesicles,central nervous system,drug delivery,ischemic stroke,Alzheimer’s disease,Parkinson’s disease,spinal cord injury,brain tumor”为英文检索词,以“外泌体,细胞外囊泡,中枢神经系统疾病,载药,脑卒中,阿尔兹海默病,帕金森病,脊髓损伤、脑肿瘤”为中文检索词,最终纳入94篇文献进行分析。结果与结论:(1)外泌体可以轻易通过血脑屏障输送蛋白质、代谢物和核酸到受体细胞中,调节细胞代谢。由于外泌体是由细胞分泌的小囊泡,具有更低的循环免疫原性,在体内循环中能够更少被巨噬细胞识别清除。(2)外泌体可以被设计为递送不同的治疗成分,包括RNA、蛋白质、化疗药物和免疫调节剂,能够将治疗成分传送至期望的目标。经过工程修饰的外泌体具有更好的靶向性,并且这种外泌体介导的传递免疫原性极低,有望为将来中枢神经系统疾病的精准治疗提供更加安全有效的方法。

人工智能在脊髓神经损伤与修复领域研究热点的可视化分析

背景:近年来人工智能逐渐兴起,在多方面应用于脊髓神经损伤与修复领域,对临床治疗也有诸多积极影响。目的:研究人工智能在脊髓神经损伤与修复领域的诊断、治疗和康复中的应用进展,明确该领域的研究热点和不足,为今后研究工作提供建议。方法:在Web of Science核心集数据库检索建库至2023年收录的人工智能在脊髓神经损伤与修复领域相关文献,使用CiteSpace 6.1.R6和VOSviewer 1.6.19软件对文献数据进行一般文献学分析、文献共被引、期刊共被引、期刊双图叠加及关键词聚类等可视化分析。结果与结论:①共筛选出1713篇文章,此领域年发文量呈波动上升趋势,其中美国占据主导地位,Kadone Hideki是发文量最多的作者,《ARCH PHYS MED REHAB》是被引用次数最多的期刊。②关键词共现和聚类分析显示,去除与检索词相近的关键词后,主要关键词被分为3个主要集群:外骨骼与运动康复(为最大核心热点)、机器学习和神经可塑性、机器人和康复训练。③关键词爆发分析显示,深度学习和人工智能在过去5年中已成为突发术语。④文献共被引和高被引文献分析结果显示,人工智能在脊髓神经损伤与修复领域热点集中于动力外骨骼(powered exoskeleton)、步态(gait)、神经电刺激(electrical nerve stimulation)、皮质内脑机接口(intracortical brain-computer interface,IBCI)、机器人(robot)、高分子生物材料(polymer biomaterials)及神经干细胞(neural stem cell)等内容。⑤人工智能在脊髓神经损伤与修复领域的研究近年来呈现上升趋势,该领域的关注点从外骨骼、电刺激等单一的治疗手段,逐渐向智能化、精准化和个性化等方向转变。⑥该领域存在一些局限性,例如数据缺失或不平衡的后果、数据准确性和可重复性低以及伦理问题(如隐私、研究透明度和临床可靠性等),未来的研究应该解决数据收集的问题,需要大样本、高质量的临床数据集来建立有效的人工智能模型;同时该领域的基因组学等机制研究十分薄弱,未来可利用类脑芯片等多种机器学习技术,运用基因编辑治疗及单细胞空间转录组等方法,进行再生相关基因上调和轴突生长结构蛋白产生等基础机制研究。