重视非编码RNA在中枢神经再生与修复中的作用研究

正脑与脊髓作为中枢神经系统,其损伤极为常见,致死率和致残率居各类创伤之首;相比于周围神经系统损伤,中枢神经受损后恢复困难,目前治疗仍缺乏突破~([1])。中枢神经系统神经细胞受损、缺失或死亡,常导致诸多神经功能障碍,引起偏瘫、失语、智力障碍、昏迷甚至死亡等。其不良预后与损伤后神经再生     

中枢神经系统少突胶质细胞-髓鞘糖蛋白受体的作用及其研究进展

中枢神经系统（central nervous system，CNS）损伤后轴突再生困难，一直是临床神经疾病治疗的难点，长期以来，人们通过各种途径寻找其原因并试图攻克这一难关。近年来的研究表明，CNS受损后轴突不能再生可能有几方面的原因：成年神经元损伤后本身的再生能力下降；胶质瘢痕的形成；神经营养因子的缺乏及轴突再生抑制蛋白的作用等。其中关于轴突再生抑制蛋白的研究，成为神经再生研究的热点，     

神经干细胞移植在创伤性脑损伤再生与修复中的作用和影响因素

创伤性脑损伤(traumatic brain injury,TBI)是一种十分常见的神经外科疾病,世界卫生组织研究表明,到2020年创伤性脑损伤将成为死亡和致残的主要疾病[1,2].每年大约有1 000万人遭受创伤性脑损伤,其中主要集中在15～ 24岁的年轻人和75岁以上的老年人.TBI后神经细胞受损、缺失或死亡,常使神经功能严重受损而导致偏瘫、失语、智力障碍或昏迷,甚至死亡.创伤性脑损伤预后较差与损伤后神经功能的缺失相关,神经功能的缺失与中枢神经系统(central nervous system,CNS)难以再生与修复有关.CNS已被证实并非不可再生,体外实验中枢神经可以再生,体内神经细胞的轴突不能再生的原因可能为环境因素和抑制因素的限制所致.因此影响神经组织再生和修复的因素,是当下研究的焦点[3-9].     

大脑老化与神经再生和卒中

大脑老化是神经退行性疾病的主要诱因。而卒中不仅是老年人的神经系统常见疾病,而且也是70岁以上老年人致残和死亡的重要原因,因此,大脑老化与卒中发病息息相关。已经证实,老年卒中患者其缺血性脑组织损伤更加严重、脑梗死面积更大、缺血后的神经功能障碍也更加显著。尽管研究已证实老龄大脑的神经再生减少,但卒中可以诱导神经再生并能有效促进神经功能恢复,这就为神经再生治疗卒中开辟了良好的途径。本文重点就大脑老化及老化后神经再生、缺血性卒中作一简要综述。     

许旺细胞在周围神经损伤修复中的作用及其可能分子机制**★

背景：周围神经损伤后神经功能的恢复一直是人们关注的焦点。许旺细胞在促神经功能恢复方面有着不可替代的作用。 目的：对国内外有关许旺细胞在促神经功能恢复方面的作用及其可能的分子机制作一综述。 方法：应用计算机检索CNKI、VIP和OVID数据库中1993-01/2010-01关于周围神经损伤的文章，在标题和摘要中以“许旺细胞，周围神经，神经再生，综述”或“Schwann Cells，Peripheral Nerve，Nerve Regeneration, Review”为检索词进行检索。选择文章内容与许旺细胞对周围神经损伤的作用有关者，同一领域文献则选择近期发表或发表在权威杂志上的文章。初检得到256篇文献，根据纳入标准选择关于许旺细胞作用机制的24篇文献进行综述。 结果与结论：许旺细胞通过多种途径作用于受损的周围神经，进而促进损伤神经功能的恢复。如何促使损伤局部许旺细胞更多的增殖将成为更好地促进损伤神经功能恢复的一大突破点。综合各方面因素，电针治疗周围神经损伤将有更好的前景。     

细胞移植与中枢神经功能缺损的治疗

中枢神经系统损伤所致神经功能缺损的治疗一直是神绛科学的难题之一。传统的中西医结合临床康复治疗效果不理想，促进内在神经再生和改善微环境的治疗前景也不乐观．神经干细胞移植为治愈中枢神经功能缺损提供了新的可能。     

中枢神经系统损伤修复与治疗性疫苗

中枢神经系统（central nerve system。CNS）损伤后，受损神经轴突不能自然再生。从而导致个体感觉、运动及认知的永久性缺失。引发严重的社会问题。因只要一部分神经纤维束连接得以再通即可完成显著的功能信号转导，因此探寻新的策略。最大程度上促进CNS损伤后修复再生具有重大意义。     

神经生长因子对颅脑损伤的保护作用

神经生长因子（NGF）具有促进神经元存活、生长发育及分化,保护受损神经元,诱导神经纤维定向生长和再生等多种效应。颅脑损伤后NGF与其受体结合,通过PI-3K—Akt、MEK—MAPK等途径调节某些基因的表达,诱导和增加某些蛋白表达（如生长相关蛋白、微管相关蛋白等）,从而保护受损的神经元,促进神经元修复、神经再生。本文就NGF的生物学效应、信号传导机制及促进颅脑损伤后神经再生的机制等研究进展进行综述。     

PirB/ROCK信号通路与成年哺乳动物中枢神经系统再生

正成年哺乳动物中枢神经系统(central nervoussystem,CNS)损伤可引起不同程度的功能障碍,修复损伤的神经功能对恢复正常的工作、生活具有重要的意义。纠正CNS再生的不利因素是实现有效修复受损神经结构和功能的研究热点之一。髓磷脂是抑制CNS再生的重要因素,而配对免疫球蛋白样受体B(paired immunoglobulin-like receptor B,Pir B)和Rho相关卷曲螺旋蛋白激酶(Rho-associatedcoiled-coil kinase,ROCK)是其中的关键因子。本文     

骨髓干细胞动员抑制脑缺血损伤神经细胞凋亡的研究进展

缺血性脑血管疾病是人类致残和死亡的主要原因,其治疗的关键在于挽救缺血半暗带濒死亡的神经元和促进损伤后神经功能的恢复.神经细胞凋亡是脑缺血后神经细胞死亡的重要途径,也是造成中枢神经损伤后神经功能缺失的重要原因.     

Aberrant reinnervation

Although great emphasis is placed on providing a satisfactory conduit for regeneration of peripheral axons after nerve repair, the quality of functional restoration is influenced as much by the quality as the quantity of axonal regeneration. Misdirected regeneration is so commonly encountered that motor axons appear to enter and regenerate to muscles in an almost random manner. Thus, when there are several choices, as usually is the case with more proximal nerve or plexus repairs, misdirected reinnervation accounts in many incidences for a poor quality of functional restoration. The regenerative capacities of type I and type II motor axons appear to differ. Proprioceptors and other sensory axons have been shown to reinnervate inappropriate end organs. Consequently, deranged central reflex modulation and disturbed orderly recruitment of motor units according to the size principle also contributes to this problem. Central re-education or adaptation to misdirected regeneration does not occur to any appreciable extent.     

Transected dorsal column axons within the guinea pig spinal cord regenerate in the presence of an applied electric field

Using an implanted battery and electrodes, we have imposed a weak, steady electrical field across partially severed guinea pig spinal cords. We have analyzed regeneration of dorsal column axons in experimental animals and sham-treated controls at 50-60 days postinjury by anterograde filling of these axons with the intracellular marker horseradish peroxidase and by employing a marking device to identify precisely the original plane of transection (J. Comp. Neurol. 250: 157-167, '86). In response to electric field applications, axons grew into the glial scar, as far as the plane of transection in most experimental animals. In a few animals axons could be traced around the margins of the lesion (but never through it). Moreover, these fibers returned to their approximate positions within the rostral spinal cord before turning toward the brain. In sham-treated controls, ascending axons were found to terminate caudal to the glial scar, and rarely were any fibers found within the scar itself. Axons were never observed to cross into the rostral cord segment. These findings suggest that an imposed electrical field promotes growth of axons within the partially severed mammalian spinal cord, that a steady voltage gradient may be an environmental component necessary for axonal development and regeneration, and that some component(s) of the scar impede or deflect axonal growth and projection.     

Transplant-derived astrocytes migrate into host lumbar and cervical spinal cord after implantation of E14 fetal cerebral cortex into adult thoracic spinal cord

Fourteen-day gestation fetal cerebral cortex homografts were transplanted into the thoracic (T6) spinal cord between the left dorsal column and dorsal horn of adult host rats. The transplants were soaked in 2.0 micrograms/ml of the lectin Phaseolus vulgaris leucoagglutinin (PHAL) prior to implantation. Transplanted host spinal cords were utilized at 7, 14, and 24 d and at 1 and 2 months postimplantation. Paraffin-sectioned spinal cords were double labeled for PHAL and glial fibrillary acidic protein (GFAP) by using FITC- and RITC-conjugated secondary antisera, respectively. Montages of FITC- and RITC-positive cells were analyzed for cells containing both fluorescences. Double-labeled cells (PHAL-GFAP) were transplant-derived astrocytes. Transplant-derived astrocytes were observed to initiate migration in the white matter columns of the host at approximately 14 d after transplantation. Double-labeled astrocytes were observed in cervical and lumbar spinal cord of the host (ca. 3.5 cm away from the center of the transplant) at 2 months postoperative. These astrocytes migrated at approximately 0.76 mm a day (after a 14-d delay). At 2 months, transplant-derived astrocytes composed as much as 50% of the astrocytes in the white matter of the host 2.0 mm from the transplant. The migrated astrocytes were hypertrophied and appeared reactive. Astrocytes in spinal gray matter only migrate about 1.0 mm from the graft-host interface. Transplant-derived astrocytes can migrate the entire length of the spinal cord white matter.     

脑源性生长因子与神经损伤的修复及再生

背景：脑源性生长因子具有促进神经元生长存活，引导轴突延伸塑型的作用。周围神经损伤后的再生和髓鞘形成需要内源性脑源性神经生长因子。 目的：归纳总结脑源性生长因子的研究现状。 方法：以中文检索词“神经再生；脑源性生长因子”和英文检索词“nerve，regeneration，BDNF”检索2000-01/2009-08中国期刊全文数据库和Pubmed数据库。纳入具有原创性、论点论据可靠的试验文章，观点明确，分析全面的文章，及文献主题与此课题关系紧密的文章。排除重复性研究和综述文章。 结果与结论：神经损伤后在髓鞘形成过程中脑源性神经生长因子通过高亲和力Trk受体和低亲和力受体P75NTR促进髓鞘形成。与神经生长因子在周围靶组织合成不同，脑源性神经生长因子主要在中枢神经系统中合成，但当周围神经受损后其mRNA表达增多，大量的实验表明正常周围神经的许旺细胞同样有少量脑源性神经生长因子表达。现在人们通过将脑源性神经生长因子基因通过病毒介导转染干细胞后移植到神经损伤区域治疗疾病，有望成为新的治疗方法。     

胶原膜引导下同种骨颗粒修复兔桡骨节段性缺损

背景：胶原膜是一种可吸收引导成骨材料,同种异体骨是较为理想的骨替代材料,但单独应用均有其不足,拟将两种材料结合使用以期达到理想效果。 目的：利用膜引导组织再生技术,观察胶原膜复合同种骨颗粒修复兔桡骨节段性骨缺损的成骨速度和质量,并与单纯胶原膜进行比较。 设计、时间及地点：同体对照观察实验,于2004-09/2005-02在中国辐射防护研究院医用组织库中心实验室完成。 材料：胶原膜规格20 mm×20 mm,由北京天新福医疗器材有限公司提供。同种异体骨颗粒按美国组织库标准制备,直径0.2~0.7 mm,由山西省医用组织库提供。 方法：健康成年新西兰大白兔40只,制备双侧15 mm桡骨缺损模型,采用同体对照方法,实验侧（左侧）缺损区移植胶原膜及同种骨粒,对照侧（右侧）仅移植胶原膜。 主要观察指标：光镜组织学观察骨缺损愈合情况,计算机图像分析仪计算骨小梁的成骨面积,扫描电镜观察缺损再生修复情况。 结果：①光镜组织学变化：实验侧新骨增生明显,迅速,以膜性化骨及软骨内化骨的方式由骨缺损周围向中央成骨或以同种骨粒为中心由周围向骨粒内成骨,最后骨膜形成,新髓腔不断扩大、再通,骨重建顺利,缺损修复完成。对照侧成骨方式以软骨化骨为主,新骨形成较同期实验侧慢,新骨成熟度不如实验组。②成骨面积图像分析：结果显示术后2,4,8周新生骨小梁成骨面积均大于同期对照侧（P < 0.05）。③扫描电镜观察：术后8周实验侧有较多分泌胶原的成骨细胞和带有较多突起的骨细胞,钙盐沉积,骨质排列开始有序。对照侧软骨与类骨质互相存在,低倍下骨基质排列无序,胶原纤维编织样排列。术后12周实验侧骨质排列有序,胶原粗大排列整齐,大量骨细胞方向有序,大量钙盐沉积,可见哈佛氏管和血管。对照侧骨质排列有序,但胶原纤维较细、基质钙化程度不如实验侧。 结论：两种方法均能成骨修复缺损,但胶原膜复合同种异体骨粒组成骨速度快,且成骨质量优于单纯胶原膜组。     

Complement components of nerve regeneration conditioned lfuid inlfuence the microenvironment of nerve regeneration

Nerve regeneration conditioned lfuid is secreted by nerve stumps inside a nerve regeneration chamber. A better understanding of the pro-teinogram of nerve regeneration conditioned lfuid can provide evidence for studying the role of the microenvironment in peripheral nerve regeneration. In this study, we used cylindrical silicone tubes as the nerve regeneration chamber model for the repair of injured rat sciatic nerve. Isobaric tags for relative and absolute quantitation proteomics technology and western blot analysis conifrmed that there were more than 10 complement components (complement factor I, C1q-A, C1q-B, C2, C3, C4, C5, C7, C8β and complement factor D) in the nerve regeneration conditioned lfuid and each varied at different time points. These ifndings suggest that all these complement components have a functional role in nerve regeneration.     

Specificity in mammalian peripheral nerve regeneration at the level of the nerve trunk

Previous studies indicate that distal stumps of transected rat peripheral nerves secrete 'tropic' factors which can attract/support axonal regeneration over distances of several mm in vivo. The present study was undertaken in order to determine if there is specificity of neurotropic interaction at the level of the nerve trunk. Proximal stumps of transected peroneal or tibial nerves were inserted into the single inlet end of Y-shaped Silastic implants and offered alternative 'lures' at the paired outlet ends (specifically, grafts of peroneal vs tibial distal stump tissue). Several weeks later, the overwhelming majority of preparations showed exclusive growth of nerve fibers in implant forks attached to 'native' (originally associated) nerve stumps. Inversion of the distal stump grafts (such that the proximal stump was facing an analogous native distal stump, but a different region of it) diminished the frequency and extent of native preference. Taken together, data suggest the possibility that there can be a specificity of nerve regeneration at the level of the nerve trunk.     

Tropic factors in reactive mammalian central nervous system tissue

Previous studies suggest that distal stumps of transected peripheral nerves contain diffusible factors which can attract/support axonal regeneration over distances of several mm in vivo. The present experiments were undertaken to determine if this is so for distal regions of traumatized central (i.e., optic) nerves. Proximal stumps of transected rat sciatic nerves were inserted into the single inlet ends of 6 mm long Y-shaped Silastic implants. Alternative ‘lures’ were attached to the paired outlets, the ability of these lures to attract/support regeneration of nerve fibers in their associated forks assessed 3.5 weeks postoperatively. Exclusive or preferential growth of nerve fibers occurred in implant forks associated with optic nerve grafts, of Elvax pellets containing homogenate obtained from previously crushed (reactive) optic nerves. Grafts of tendon, as well as homogenate from unoperated optic nerve had no effect.Results suggest that, with repect to the assay used, degenerating optic nerve tissue contains factor(s) which can attract/support regenerating nerve fibers.     

Numbers of regenerating axons in parent and tributary peripheral nerves in the rat

This study is concerned with numerical parameters of axonal regeneration in peripheral nerves. Our first finding is that the number of axons that regenerate into the distal stump of a somatic nerve at a particular time after transection is partially dependent on the type of lesion used to interrupt the axons. The second question concerns the proportion of axons that regenerate into the distal stump of a parent nerve compared to the proportions that regenerate into tributary nerves that arise from the parent. The proportions of regenerated myelinated axons in the nerve to the medial gastrocnemius muscle and myelinated and unmyelinated axons in the sural nerve are the same as the proportions of myelinated and unmyelinated axons that regenerate into the distal stump of the sciatic nerve for the crush, 0 and 4 mm gap transections. Proportionally fewer axons regenerate into the tributary nerves following the 8 mm gap transection, however. This implies that the length of the gap has an influence on whether or not axons in tributary nerves regenerate in concert with axons in the distal stump of the parent nerve. The unmyelinated fibers in the nerve to the medial gastrocnemius muscle are different because they do not regenerate in proportion to those in the distal stump of the sciatic nerve. We also provide evidence to indicate that myelinated axons branch whereas unmyelinated fibers end blindly when they enter the distal stump after crossing a sciatic nerve transection. Finally the normal arrangement of perineurial cells seems to be disrupted after the sciatic nerve regenerates across a gap.