大鼠脊髓损伤局部空洞瘢痕的量化分析

目的: 对脊髓损伤后形成的空洞和瘢痕进行量化分析。方法: 成年雄性SD大鼠 32只, 随机分为术后7、14、21和 28d4组。切断大鼠T9 平面脊髓制备脊髓完全横断损伤模型, 术后相应时间灌注取材, 切片行HE、天狼猩红染色以及GFAP (胶质细胞酸性蛋白 )、NF (神经丝蛋白 ) 免疫荧光染色。计算机图像分析测算脑膜瘢痕面积, 胶质瘢痕面积, 空洞直径和脊髓残端间距。结果: 脑膜瘢痕面积为 0. 052mm2, 胶质瘢痕面积为 0 .026mm2。脑膜瘢痕面积接近胶质瘢痕的 2倍, 差异显著 (P<0. 05)。脑膜瘢痕和胶质瘢痕主要成分均为Ⅰ型胶原。在胶质瘢痕内可见NF阳性标记的再生神经纤维, 而在脑膜瘢痕中却全然没有, NF标记的再生神经纤维无法逾越脑膜瘢痕。结论:空洞和瘢痕形成了再生神经纤维无法逾越的巨大障碍, 脑膜瘢痕要甚于胶质瘢痕。在脊髓损伤修复中移植桥接脊髓就成为必须。     

脊髓损伤后胶质瘢痕在神经再生过程中作用的探讨

在脊髓损伤再生修复的研究中,胶质瘢痕一直是非常重要的研究方向。几十年来,主流观念普遍认为胶质瘢痕是神经再生的物理屏障,而且其分泌的抑制因子会阻碍神经纤维再生。随着技术发展和研究深入,脊髓损伤修复研究领域许多传统主流观念都受到了新生力量的冲击,对胶质瘢痕的认识也不例外。该文简要回顾自20世纪30年代至今数代研究人员对脊髓损伤后胶质瘢痕组织的研究历史,并综述胶质瘢痕在神经再生与功能重建方面作用的争议及进展。希望能更好梳理和认清胶质瘢痕在脊髓损伤后的角色及定位,以期有效助力攻克脊髓损伤修复这一世界难题。     

蛛网膜囊肿误诊为腰椎间盘突出症两例报告

例1,张××,男性,54岁,干部,住院号154649。腰痛十三年,进行性疼痛加重伴左下肢麻木、胀痛三年于84年3月1日以腰椎间盘突出症收入院。 十三年前因外伤出现腰痛,未经特殊治疗逐渐减轻。以后反复腰痛,时轻时重。83年因外伤致腰痛伴左下肢麻木,半年后出现     

星形胶质细胞活化与脊髓损伤修复

脊髓损伤后星形胶质细胞活化并分泌多种细胞外基质共同组成的胶质瘢痕,是阻碍神经轴突再生的重要因素。星形胶质细胞活化与TGF-β、Rheb-mTOR等信号通路的激活密切相关,并受到细胞外基质中高分子量透明质酸抑制作用的影响。细胞周期调控是近年报道的抑制星形胶质细胞活化、促进轴突再生的重要手段,而降解星形胶质细胞活化后分泌的多种抑制性蛋白,尤其是硫酸软骨素蛋白多糖则早已受到关注。胶质瘢痕对于脊髓损伤的修复是一把双刃剑,因此干预星形胶质细胞活化的时机亦显得非常重要。     

星形胶质细胞在脊髓损伤中作用的研究进展

正近年来SCI的发生率在我国乃至全世界呈明显上升趋势~([1])。但SCI的修复是尚未解决的医学难题,而神经轴突的再生是SCI后功能重建的重要基础。小胶质细胞的激活、星形胶质细胞(astrocyte,AS)的增殖活化和胶质瘢痕的形成是阻碍轴突再生的关键因素。AS的增殖活化并分泌多种细胞外基质共同形成神经胶质瘢痕是抑制SCI修复     

腰_5原发性神经根管狭窄

唐××,男,48岁,农工,住院号109410 腰痛、左下肢麻痛八年,廿年前腰扭伤治愈,八年前腰痛再发,近四年腰痛加重伴左下肢麻木,发作性、晨起时腰尤其是腿剧痛难忍致额头冒出汗珠,约2小时后渐减轻,后可活动,尚可进行劳动,掭作电焊。     

脂氧素A4对大鼠局灶性脑缺血再灌注损伤时炎性反应的影响

目的 探讨脂氧素A4对大鼠局灶性脑缺血再灌注损伤时炎性反应的影响.方法 雄性健康SD大鼠56只,体重200～250 g,随机分为3组:假手术组(S组,n=8),缺血再灌注组(I/R组,n=24),脂氧素A4组(LXA4组,n=24).采用线栓法阻塞大鼠右侧大脑中动脉制备局灶性脑缺血再灌注模型,LXA4组脑缺血后5 min经侧脑室注射脂氧素A4 0.03 nmol/5 μl,S组和I/R组注射等容量生理盐水,缺血2 h后拔出线栓行再灌注.再灌注24 h时行神经功能缺陷评分,然后断头取脑,光镜下观察病理学,采用比色法检测髓过氧化物酶活性,免疫组织化学方法检测星形胶质细胞和小胶质细胞的活化,ELISA法检测再灌注1、6、12、24和48 h时TNF-α、IL-β、转化生长因子β(TGF-β1)及IL-10的含量.结果 与S组比较,I/R组大鼠神经功能缺陷评分、髓过氧化物酶活性、TNF-α、IL-1β、TGF-β1和IL-10的含量升高,星形胶质细胞和小胶质细胞的活化数目增多(P<0.05);与I/R组比较,LXA4组神经功能缺陷评分、髓过氧化物酶活性、TNF-α和IL-1β含量降低,TGF-β1,和IL-10含量升高,星形胶质细胞和小胶质细胞的活化数目减少(P<0.05).病理结果显示:LXA4组脑缺血再灌注损伤程度较I/R组减轻.结论 脂氧素A4可通过抑制炎性反应减轻大鼠局灶性脑缺血再灌注损伤.     

硫酸软骨素蛋白多糖在脊髓损伤病理机制中的作用

脊髓损伤（spinal cord injury,SCI）是由各种因素导致的脊髓损伤平面以下的感觉、运动及其他系统功能紊乱的中枢神经系统疾病。SCI不仅给患者带来严重的身心伤害,还会对家庭和社会造成巨大的经济负担。静息状态的星形胶质细胞被激活后转化为反应性星形胶质细胞（reactive astrocytes,RAS）是脊髓受损后所导致的一系列临床表现的病理基础。其主要作用是保护正常组织和神经元、减少损伤区域的水肿及炎性反应、促进损伤处血管再生。在脊髓损伤的早期,RAS可以通过减轻并修复损伤、保护血脑屏障、为神经元提供适宜的生存环境等方式对中枢神经系统起到保护作用。随着损伤的进展,神经元会出现脱髓鞘和突触连接的中断,加上氧化应激的产生,会导致细胞的凋亡、成纤维细胞的侵袭和炎症反应的持续发展,促使RAS不断分泌并上调损伤处硫酸软骨素蛋白多糖（chondroitin sulphate proteoglycans,CSPGs）的表达,最终在损伤区域的周围形成神经胶质瘢痕,以隔离损伤部位,阻止病变的进一步发展。所以在后期的损伤修复过程中,胶质瘢痕的形成不仅阻碍了轴突的延长,还严重影响了轴突的再生。因此,星形胶质细胞的活化和CSPGs的表达在SCI和修复过程中是一把双刃剑：损伤早期RAS可以防止炎症的扩大,避免更多细胞的损伤和坏死;后期会导致轴突再生的失败。所以在损伤后期消除RAS分泌的CSPGs所引发的胶质瘢痕,是SCI修复过程中的重要环节。笔者对CSPGs在SCI中的作用做一综述,为SCI的临床治疗提供参考。     

降纤酶对脊髓损伤后纤维蛋白原沉积及瘢痕形成的影响

纤维蛋白原是具有调节凝血、炎症及组织修复功能的多效蛋白.当脊髓损伤(SCI)、多发性硬化等导致血脑屏障或血神经屏障破坏时,纤维蛋白原渗入神经组织,立即转化为纤维蛋白在神经系统沉积,与胶质瘢痕形成相关.应用遗传或药物耗竭纤维蛋白原,能减少皮质损伤后转化生长因子( TGF)－β激活、Smad 2磷酸化、神经胶质细胞活化,而将纤维蛋白原定位注入大脑皮层能引起星形胶质细胞增生[1].我们采用改良AlLen's法制备SCI模型,通过腹腔注射降纤酶,观察降纤酶对SCI局部纤维蛋白原沉积及胶质瘢痕形成的影响.     

中药颈椎Ⅰ号治疗模拟颈神经根炎病理学观察

目的　为了观察中药颈椎 号对模拟颈神经根炎的疗效及作用机理。方法　将 96只模拟颈神经根炎 Wistar大鼠随机分为 4组 :颈椎 号中剂量组、颈椎 号高剂量组、颈复康组及空白对照组 ,分别给予颈椎 号中剂量、高剂量、颈复康及凉开水 ,于造模后 3天、 7天、 14天、 4 2天 ,取神经根进行病理学观察。结果　颈椎 号中剂量、高剂量可以明显减轻模型鼠颈神经根的充血、水肿、淋巴细胞浸润等炎症反应 ,减轻成纤维细胞和胶原纤维的增多 ,减轻瘢痕化 ,促使神经功能恢复。结论　颈椎 号对模拟颈神经根炎具有良好的疗效     

Isolated intervertebral disc resorption. A source of mechanical and inflammatory back pain?

Seven patients underwent anterior interbody spinal fusions to alleviate pain due to resorption of an intervertebral disc. The anterior annulus of the discs at operation was inflamed. The specimens were studied histologically, and the findings are discussed. The demonstration of inflammation in the anterior annulus together with the recent identification of nerve fibres in the anterior annulus now allows a better understanding of discogenic pain and its management.     

Neuropeptide tyrosine (NPY): a newly discovered peptide is present in the mammalian respiratory tract.

Neuropeptide tyrosine (NPY), a newly discovered peptide known to modulate blood vessel diameter and smooth muscle tone, has been found in many mammalian organs. Its distribution is similar to that of sympathetic nerve fibres and NPY immunoreactivity has been found in noradrenergic ganglion cells. In a study of the respiratory tract of four mammalian species--man, cat, guinea pig, and rat--NPY immunoreactivity has been localised to nerve fibres. NPY immunoreactive nerve fibres were found in the adventitia of blood vessels and in the airway smooth muscle. Its distribution was strikingly similar to that of sympathetic nerve fibres as demonstrated by dopamine-beta-hydroxylase antibodies. The mean (SD) concentrations of NPY in the guinea pig respiratory tract, as determined by radioimmunoassay of tissue extracts, were: upper trachea 3.3 (0.7), lower trachea 2.0 (0.5), and major bronchus 3.5 (1.1) pmol/g. During developmental studies in man NPY immunoreactive nerve fibres were first observed at 20 weeks' gestation in the trachea, and fibres gradually extended down into the intrapulmonary airways after birth. NPY immunoreactive nerve fibres have a distribution and developmental pattern similar to that of sympathetic nerve fibres in the respiratory tract. The finding of NPY immunoreactivity in nerve fibres in the mammalian respiratory tract adds to the growing number of peptides having potent biological actions found in this organ, and shows that the lung possesses a rich peptidergic system, which may influence pulmonary function.     

Nerve regeneration following primary repair

Summary In nine selected cases a primary nerve repair was done. In all these patients a special suture was used. Applying clinical and neurophysiological tests, regeneration of the motor and sensory nerve fibres was followed for two years.A remarkable difference in growth rates of sensory and motor nerve fibres was observed. The average rate of growth of sensory nerve fibres was 5 mm a day, and of motor nerve fibres it was 1.7 mm a day. At the end of a two years' interval after operation, good recovery from the initial muscular atrophy was observed in all but two cases. Function of previously denervated muscles was nearly normal. Discrimination of points 4–10 mm apart was possible. Normal terminal conduction times along motor nerve fibres were found in five eases. Slightly prolonged times were found in four. Calculated conduction velocities in sensory nerve fibres were half to three quarters of normal times.All patients resumed their previous occupations.     

Sensory hypoinnervation in club foot

We have compared the density of nerve fibres in the synovium in club foot with that of specimens obtained from the synovium of the hip at operations for developmental dysplasia. The study focused on the sensory neuropeptides substance P; calcitonin gene-related peptide; protein gene product 9.5, a general marker for mature peripheral nerve fibres; and growth associated protein 43, a neuronal marker for new or regenerating nerve fibres. In order to establish whether there might be any inherent difference we analysed the density of calcitonin gene-related peptide-positive nerve fibres in the hip and ankle joints in young rats. Semi-quantitative analysis showed a significant reduction in the number of sensory and mature nerve fibres in the synovium in club foot compared with the control hips. Calcitonin gene-related peptide (CGRP) positive fibres were reduced by 28%, substance P-positive fibres by 36% and protein gene product 9.5-positive fibres by 52% in club foot. The growth associated protein 43-positive fibres also seemed to be less in six samples of club foot. No difference in the density of CGRP-positive nerve fibres was observed in the synovium between ankle and hip joints in rats. The lack of sensory input may be responsible for the fibrosis and soft-tissue contractures associated with idiopathic club foot.     

神经生长因子与睫状神经营养因子促进感觉和运动纤维再生的差异性研究

目的探讨神经生长因子(NGF)与睫状神经营养因子(CNTF)对不同类型神经纤维再生的促进作用。方法利用梭形双通道桥接管桥接32只SD大鼠坐骨神经10mm缺损。将动物随机分为两组,A组:两支管内均加入医用几丁糖凝胶;B组:两支管内加入医用几丁糖凝胶后分别注入NGF和CNTF。术后12、16周行电生理检测和组织化学染色。结果Holmes银染示B组CNTF侧再生纤维均较NGF侧再生神经外膜薄,纤维排列整齐,粗细均匀;硫代乙酰化胆碱染色示B组CNTF侧呈棕红色的阳性纤维较NGF侧数目较多,粗细均匀,排列整齐;而碳酸酐酶染色则显示B组NGF侧呈褐色的阳性神经纤维密度及排列稍较CNTF多。电生理检测见NGF侧再生神经复合肌肉动作电位(CMAP)和皮层体感诱发电位(CSEP)的潜伏期较CNTF侧长,而波幅较低(P<0.05)。结论CNTF促进运动纤维再生的相对作用较强,而NGF具有相对较强的促进感觉纤维再生的作用。     

A study of the myelinated fibres in the branches of the pelvic plexus

In a 20-year-old human female specimen the nerves to the pelvic organs were dissected and analysed. The gross anatomy of the branches of the pelvic plexus was described. The composition of these nerves was studied and the sizes and distribution of the diameter of a great part of the myelinated nerve fibres were measured and analysed. It was confirmed that the ventral roots S2 and S3 contain many nonmyelinated nerve fibres. There are direct connections between the sacral sympathetic chain and the pelvic plexus. They contain myelinated fibres with sizes as large as 11 μm. There are two different groups of fibres which supply the bladder, one on the dorsal side, mainly nonmyelinated (postganglic sympathetic?), and another group to the lateral side which contains many thin myelinated fibres (parasympathetic preganglionic?). The pelvic plexus and its branches are fixed to the vagina and the rectum. Surgical interventions in this area and perhaps also childbirth can damage the nerve supply to the bladder and the urethra. The functional disturbances of the bladder after such interventions can depend on what group of nerve fibres is most seriously damaged. The large number of thick myelinated fibres which reach the ventro lateral side of the urethra makes it highly probable that these fibres innervate the intrinsic striated urethral musculature. The large number of nonmyelinated nerve fibres in the nerves to the m. levator ani probably innervate smooth muscle tissue which is found in the fasciae of the pelvic floor.     

The sensory-motor bridge neurorraphy: an anatomic study of feasibility between sensory branch of the musculocutaneous nerve and deep branch of the radial nerve

Introduction: Restoring elbow flexion remains the first step in the management of total palsy of the brachial plexus. Non avulsed upper roots may be grafted on the musculocutaneous nerve. When this nerve is entirely grafted, some motor fibres regenerate within the sensory fibres quota. Aiming potential utilization of these lost motor fibres, we attempted suturing the sensory branch of the musculocutaneous nerve onto the deep branch of the radial nerve. The objective of our study was to assess the anatomic feasibility of such direct suturing of the terminal sensory branch of the musculocutaneous nerve onto the deep branch of the radial nerve. Methods: The study was carried out with 10 upper limbs from fresh cadavers. The sensory branch of the musculocutaneous muscle was dissected right to its division. The motor branch of the radial nerve was identified and dissected as proximally as possible into the radial nerve. Then, the distance separating the two nerves was measured so as to assess whether direct neurorraphy of the two branches was feasible. Results: The excessive distance between the two branches averaged 6 mm (1–13 mm). Thus, direct neurorraphy of the sensory branch of the musculocutaneous nerve and the deep branch of the radial nerve was possible. Conclusions: When the whole musculocutaneous nerve is grafted, some of its motor fibres are lost amongst the sensory fibres (cutaneous lateral antebrachial nerve). By suturing this sensory branch onto the deep branch of the radial nerve, “lost” fibres may be retrieved, resulting in restoration of digital extension. © 2011 Wiley‐Liss, Inc. Microsurgery, 2011.     

Sensory endings in skin grafts and scars after extensive burns

Fifteen patients who underwent a split thickness skin graft operation for full thickness burns and six patients with postburn scars were biopsied after a standard aesthesiological examination completed with Weber and Dellon tests. A semiquantitative evaluation was performed on immunohistochemically stained sections to determine the presence or absence of PGP 9.5 immunoreactive intraepithelial fibres, complex sensory receptors, nerve fibres in the dermal papillae, vessel-innervating fibres, gland-innervating fibres, and nerve trunks in the deep dermis. The reinnervation pattern was similar in grafts and scars. With regard to sensory receptors, free nerve endings and Merkel-neurite complexes were observed. Statistical analysis suggested a significant correlation between sensibility and the amount of regenerated nerve structures (particularly in the epidermis and dermal papillae).     

Origin, course, and endings of abnormal enteric nerve fibres in Hirschsprung's disease defined by whole-mount immunohistochemistry

Accurate delineation of the intramural pathway of abnormal enteric nerve fibres in Hirschsprung's disease has previously proved impossible because the neural network is invariably transected in conventional histological sections. With the technique of wholemount immunohistochemistry (WI), the bowel segment is converted into a rectangular sheet and the serosa, long muscle (LM), circular muscle (CM), submucosa, and mucosa are separated into layers to allow each nerve plexus to be examined intact and neural pathways traced. The entire resected bowel specimens of nine HD infants and five infants serving as controls were investigated, using neuron-specific enolase and vasoactive intestinal peptide (VIP) for WI. The major new findings are (1) More VIP fibres were observed in aganglionic bowel with WI than with conventional sections; (2) Thick nerve trunks in aganglionic bowel do not descend from intrinsic neurons of oligoganglionic bowel as previously suggested, but have an extrinsic origin, accompanying blood vessels as small nerves initially, expanding subsequently, and ending blindly in submucosa; (3) CM nerve fibres follow muscle fibres concentrically for long distances in aganglionic bowel; and (4) LM nerve fibres meander in spirals in aganglionic bowel instead of running straight. This study shows that (1) WI is highly sensitive; (2) nerve fibres in aganglionic bowel have an extrinsic origin; and (3) innervation abnormalities in Hirschsprung's disease are not only quantitative but qualitative.     

Nerve fibre counts for an intercostal nerve to cauda equina nerve root anastomosis

Mean nerve root diameters of thoracal, lumbal and sacral roots have been determined and the corresponding cross section areas calculated. The myelinated axons of these roots have been counted and the axon densities calculated. The myelinated axons of 3 lower intercostal nerves have also been counted. One intercostal nerve has with about 9,000 myelinated fibres enough axons for the regeneration of the ventral (3,000) and dorsal (16,000) myelinated fibres of the sacral roots 3 and 4 together. One intercostal has enough nerve fibres to reconstruct urinary bladder and bowel function on one side. The importance of performing a nerve anastomosis which considers functional aspects has been emphasized.