硫酸软骨素酶ABC对脑损伤后胶质瘢痕影响的实验研究

目的 探讨硫酸软骨素酶ABC(chABC)对脑损伤后胶质瘢痕组织的影响.方法 38只Wistar大鼠按随机数字表法分成5组:正常对照组(n=2)、模型组(n=9)、1.0 U/mL chABC治疗组(n=9)、2.5 U/mL chABC治疗组(n=9)、5.0 U/mL chABC治疗组(n=9),后4组采用自由落体撞击法制作大鼠脑损伤模型,造模后即刻在后3组大鼠局部脑皮层下1 mm处注射不同浓度chABC 2μL,正常对照组不做任何处理.造模后1、2、4周取脑组织标本行HE染色,分别应用免疫组化染色和Western blotting检测硫酸软骨素多聚蛋白糖(CSPGs)的表达.结果 HE染色显示损伤后2周模型组大鼠脑皮层大量星形胶质细胞聚集,不同浓度chABC治疗组损伤部位的星形胶质细胞聚集较模型组减少,以5.0U/mL chABC治疗组明显.免疫组化染色显示模型组,1.0、2.5、5.0U/mL chABC 治疗组损伤后2周大鼠脑组织CSPGs分泌均较正常对照组增加,差异有统计学意义(P＜0.05);与模型组比较,5.0 U/mL chABC治疗组大鼠脑组织CSPGs分泌减少,差异有统计学意义(P＜0.05).Western blotting检测显示造模后1、2、4周不同浓度chABC治疗组CSPGs表达均较模型组低,差异有统计学意义(P＜0.05);模型组和2.5、5.0 U/mL chABC治疗组大鼠脑组织中CSPGs的表达在造模后1、2、4周逐渐降低,差异有统计学意义(P<0.05).结论 chABC能降解胶质瘢痕中主要抑制分子CSPGs,改善脑损伤后局部轴突再生的抑制性微环境,且高浓度(5.0U/mL)chABC表现最明显.

Abstract：

Objective To explore the effect of chondroitin sulfate enzyme ABC (chABC) on glial scar in rat models of brain traumatic injury (TBI). Methods Thirty-eight Wistar rats were randomly divided into 5 groups, including normal control group (n=2), model group (rat models of TBI,n=9), 1.0 U/mL chABC treatment group (n=9), 2.5 U/ml chABC treatment group (n=9) and 5.0 U/ml chABC treatment group (n=9). After performing TBI by free falling in the later 4 groups, rats of the model group were given no treatment, while those of the other 3 groups were administrated with different concentrations of chABC by local injection respectively. One, 2 and 4 w after TBI, HE staining was performed on the brain tissues of these rat models;and immunohistochemical assay and Western blotting were employed to evaluate the secreting of chondroitin sulfate proteoglycans (CSPGs) and the therapeutic effect of chABC on glial scar. Data were statistically analyzed using t-test. Results Pathological test revealed the scars in the treatment groups were significantly fewer than those in the model group 2 w after TBI, with 5.0 U/mL chABC treatment group enjoying the fewest level (P<0.05). Immunohistochemical assay showed that the secreting of CSPGs in the treatment groups and model group was significantly increased than that in normal control group 2 w after TBI (P<0.05);the 5.0 U/ml chABC treatment group showed an obvious reduction of CSPGs secreting as compared with the model group (P<0.05). Western blotting indicated that the treatment groups showed an obvious reduction of CSPGs secreting as compared with the model group 1, 2 and 4 w after TBI (P<0.05);an obvious gradual reduction of CSPGs secreting in the model group, 2.5 and 5.0 U/ml chABC treatment groups was noted 1, 2 and 4 w after TBI (P<0.05). Conclusion ChABC could degrade the glial scar by degrading the CSPGs molecules and improve the microenvironment of local axonal regeneration after TBI;In this experiment, the highest concentration of chABC (5U/ml) shows the best effect on removing the glial scar.     

硫酸软骨素酶ABC治疗脊髓损伤的研究进展

脊髓损伤后在损伤部位周围形成的神经胶质瘢痕是轴突不能有效再生的主要障碍,胶质瘢痕由星形胶质细胞和硫酸软骨素蛋白聚糖组成。硫酸软骨素蛋白聚糖的基本结构是核心蛋白和葡胺聚糖链共价交连,其中抑制轴突生长的作用大部分是通过葡胺聚糖链介导的。硫酸软骨素酶ABC能特异性破坏硫酸软骨素蛋白聚糖的葡胺聚糖链,将硫酸软骨素蛋白聚糖分解成核心蛋白和碳水化合物短链,从而降低胶质瘢痕的阻碍作用使轴突的再生能力加强,神经功能得到改善。实验研究证明鞘内注射硫酸软骨素酶ABC治疗大鼠脊髓损伤取得良好结果,利用行为学评分评价硫酸软骨素酶ABC的治疗效果也证明它能促进脊髓损伤大鼠运动功能的恢复。     

硫酸软骨素酶ABC Ⅰ分泌型真核表达质粒的构建

目的 建立硫酸软骨素酶ABC Ⅰ(ChABC Ⅰ)的分泌型真核表达载体,并在胶质瘤细胞系中对其表达情况进行观察.方法 以真核表达载体pCDNA3.1/V5/HIS A为载体,将基底膜40蛋白信号肽编码区和ChABC Ⅰ成熟肽段编码区串联插入其多克隆位点,构建分泌型真核表达质粒pCDNA-BMS-CABC Ⅰ.采用该质粒转染人胶质瘤细胞系TJ905,培养3 d后将培养液上清液行SDS-PAGE和免疫印迹分析.结果 考马斯亮蓝染色显示有新条带出现,条带的相对分子质量大小与理论值一致,免疫印迹检测显示有V5免疫反应性特异性条带出现.结论 该真核表达载体可介导硫酸软骨素酶ABC Ⅰ在神经胶质细胞来源的细胞中以分泌蛋白形式表达.     

联合应用甲壳素导管与IGF-1对大鼠坐骨神经再生的研究

本实验探讨联合应用甲壳素导管与IGF-1对大鼠坐骨神经再生功能的影响,为治疗周围神经损伤提供科学依据。1实验方法健康雄性SD大鼠48只,随机分为3组,每组16只,制备双侧大鼠坐骨神经缺损模型(神经缺损10mm),以可吸收甲壳素神经导管桥接神经两断端形成神经再生室。A组为空白对照组:神经再生室内注入等渗生理盐水20μL;B组为对照组:神经再生室内注入明胶溶液20μL;C组为实验组:神经再生室内注入IGF-1凝胶20μL。术后4周、8周收集标本并观察再生神经的大体形态,检测神经传导速度,并进行特殊染色,S-100免疫组化检测,使用统计软件SPSS 17.0进行统计学分析。     

SD大鼠动眼神经不同部位损伤后对靶器官特异性支配的实验研究

目的研究不同部位损伤对Sprague-Dawley（SD）大鼠动眼神经功能修复的影响及可能机制。方法实验Ⅰ组大鼠（n=24）经幕下、实验Ⅱ组（n=24）大鼠经眶上裂干预动眼神经，术后通过前庭眼反射评估眼外肌在垂直、水平方向的恢复程度。经右侧上直肌注射辣根过氧化酶（HRP），逆行追踪中脑动眼神经核团内神经元分布；48h后行动眼神经组织学、解剖学研究。结果实验Ⅰ组大鼠支配上直肌的神经纤维有45％～51％由对侧中脑运动神经元发出：实验Ⅱ组81％～87％由对侧中脑运动神经元发出，神经元在中脑的分布更接近正常大鼠。实验Ⅱ组大鼠眼外肌功能恢复程度明显优于实验Ⅰ组大鼠。结论动眼神经损伤部位距离眼外肌越近，最终的神经功能恢复水平越好，这可能与再生神经纤维通过损伤部位时的迷行程度相关。     

维生素Bl、B12对Wistar大鼠坐骨神经损伤保护作用的实验研究

目的：探讨维生素B1、B12对周围神经损伤的保护作用。方法：以Wistar大鼠坐骨神经损伤为动物模型，设立四个对照组，用坐骨神经功能指数、电生理、病理形态计量学及电镜下的超微结构进行研究。结果：维生素B1、B12能促进wistar大鼠坐骨神经损伤后的有髓神经纤维再生，能促进感觉、运动神经纤维的恢复、促进雪旺细胞增殖。结论：维生素B1、B12是一种有效的治疗周围神经损伤的药物。     

大鼠坐骨神经损伤后神经与肌肉中一氧化氮合酶基因的表达

目的：探讨外周神经机械损伤对神经和所支配肌肉中神经型一氧化氮合酶（nNOS）和诱导型一氧化氮合酶（iNOS）基因表达的影响。方法：12只雌性SD大鼠分为4组，分别用止血钳挤压右侧坐骨神经30分钟、1、2和5小时，然后取右侧从骨神经和腓肠肌作为实验组材料，取左侧为自体正常对照。Trizol法提取样品总RNA。应用RT-PCR法和RNA酶保护试验（RPA）法测定2种NOS的表达，以2，3-二羟基丙醛-3-磷酸脱氢酶（GAPDH）为内参。PCR电泳带和PRA杂交带的密度测定采用NIH图像分析软件。结果：与自体对照比较，神经组织在损伤各时间段中2种NOS表达基本不变。肌肉组织的nNOS在1小时组中表达升高，2小时组下降，5小时组升高。INOS在1和2小时组中表达下降，5小时组升高。结论：神经机械损伤后神经短期内对神经自身NOS表达无影响，但对所支配组织中NOS表达产生影响，这种影响与非NOS的神经信号变化相关。     

压榨性坐骨神经损伤早期髓内炎症因子诱导型一氧化氮合酶及环氧合酶2表达的时序性

目的：研究炎症因子iNOS和COX-2在周围神经损伤早期的时空表达规律。方法：健康成年SD大鼠48只，随机分为正常组（n =8）、假手术组（n =8）和右侧坐骨神经压榨组(n =32)，实验组根据动物存活时间（6, 12, 24和72小时）再分为4组（每组n =8）,免疫组织化学方法检测L4～6脊髓内iNOS、COX-2的表达变化。结果：①正常组及假手术组动物L4～6脊髓内iNOS、COX-2呈低表达，两者比较差异无统计学意义(P >0.05)。②坐骨神经损伤后：损伤侧前、后角损伤侧iNOS和 COX-2免疫阳性染色强度随损伤时间逐渐增加，各时间点损伤侧前、后角分别与对侧和正常组相比差别有统计学意义(P <0.05)。结论：坐骨神经压榨损伤后早期iNOS和COX-2在脊髓内的表达呈上升趋势，提示iNOS和COX-2可能参与了周围神经损伤后炎性免疫反应的发生演进和神经性疼痛过程     

他克莫司与肌源性干细胞联合应用对去细胞异体神经支架移植后神经再生和修复作用的影响

背景：肌源性干细胞作为种子细胞用于制备组织工程化人工神经已经被越来越多的学者所接受。他克莫司不仅具有抗免疫排斥的效果,还具有强大的促进神经再生和修复的作用。那么能否将两项因素与去细胞异体神经支架形成一个桥接体,既能抑制异体移植的免疫反应,又能有效促进损伤神经的再生与修复？ 目的：采用理化联合处理方法制备去细胞异体神经支架,探讨肌源性干细胞与免疫抑制剂他克莫司联合应用对去细胞异体神经支架移植后神经再生及功能恢复的影响。 方法：SD大鼠坐骨神经经脱细胞处理后形成异体神经桥接体。用100 μL微量注射器将含他克莫司与肌源性干细胞的凝胶注入异体神经支架,用以修复大鼠的坐骨神经缺损。32只成年SD大鼠,随机分为4组,每组8只。切断其左侧坐骨神经造成10 mm 的缺损。他克莫司+肌源性干细胞组、肌源性干细胞组、他克莫司组以注射植入后的异体神经进行桥接;对照组仅注入透明质酸凝胶。术后8,12周进行坐骨神经指数和神经电生理测定。术后12周进行大体观察,神经组织学和超微结构观察。 结果和结论：在同一时点他克莫司+肌源性干细胞组坐骨神经功能指数、坐骨神经运动传导速度恢复率、移植体及远段有髓纤维计数均优于其他3组(P < 0.05)。各组神经移植体粗细基本正常,表面大量血管分布,与周围组织轻度粘连;他克莫 司+肌源性干细胞组较其他3组再生神经纤维更加密集、排列规则整齐;移植体许旺细胞大量增殖,移植体中央及远段内的有髓神经纤维密度、直径高于肌源性干细胞组、他克莫司组,微束之间结缔组织少,接近于正常。说明肌源性干细胞和他克莫司联合应用促进去细胞异种神经移植的神经再生与功能恢复的效果优于单独应用。肌源性干细胞和他克莫司在周围神经损伤修复中是一对具有协同作用的因子。 关键词：周围神经损伤;异体神经移植;神经再生;肌源性干细胞;他克莫司 doi:10.3969/j.issn.1673-8225.2010.03.003     

吗替麦考酚酯对大鼠弥漫性轴索损伤后脑干胶质细胞激活及硫酸软骨素表达的影响简

目的探讨吗替麦考酚酯（MMF）对大鼠弥漫性轴索损伤（DAD后脑干胶质细胞激活及硫酸软骨素表达的影响。方法将72只DAI后SD大鼠随机分为3组：空白对照组、生理盐水治疗组（NS组）、吗替麦考酚酯治疗组（MMF组）。MMF组腹腔注射MMF（100mg／kg）干预;NS组腹腔注射等量生理盐水;空白对照组只作针扎刺激,不注射任何药物。伤后7、14、28d处死3组大鼠,取大鼠脑干进行巨噬细胞一小胶质细胞质抗原（ED-1）、胶质纤维酸性蛋白（GFAP）和硫酸软骨素（CS）免疫组化染色,检测活化小胶质细胞、活化星形胶质细胞、硫酸软骨素蛋白聚糖,并以累积光密度（IOD）值进行定量评估。结果在伤后不同时间点,MMF组活化小胶质细胞、活化星形胶质细胞、硫酸软骨素蛋白聚糖IOD值均显著低于NS组与空白对照组（P〈0．05）;而Ns组和空白对照组之间无统计学差异（P〉0．05）。结论MMF可抑制大鼠DAI后脑干小胶质细胞和星形胶质细胞激活,还可降低cs表达。     

Intraspinal microinjection of chondroitinase ABC following injury promotes axonal regeneration out of a peripheral nerve graft bridge

Chondroitin sulfate proteoglycans (CSPG) within the glial scar formed after central nervous system (CNS) injury are thought to play a crucial role in regenerative failure. We previously showed that delivery of the CSPG-digesting enzyme chondroitinase ABC (ChABC) via an osmotic minipump allowed axonal regeneration and functional recovery in a peripheral nerve graft (PNG)-bridging model. In this study, we sought to overcome the technical limitations associated with minipumps by microinjecting ChABC directly into the distal lesion site in the PN bridging model. Microinjection of ChABC immediately rostral and caudal to an injury site resulted in extensive CSPG digestion. We also demonstrate that this delivery technique is relatively atraumatic and does not result in a noticeable inflammatory response. Importantly, microinjections of ChABC into the lesion site permitted more regenerating axons to exit a PNG and reenter spinal cord tissue than saline injections. These results are similar to our previous findings when ChABC was delivered via a minipump and suggest that microinjecting ChABC is an effective method of delivering the potentially therapeutic enzyme directly to an injury site.     

Rolipram-induced elevation of cAMP or chondroitinase ABC breakdown of inhibitory proteoglycans in the extracellular matrix promotes peripheral nerve regeneration

The inhibitory growth environment of myelin and extracellular matrix proteoglycans in the central nervous system may be overcome by elevating neuronal cAMP or degrading inhibitory proteoglycans with chondroitinase ABC (ChABC). In this study, we asked whether similar mechanisms operate in peripheral nerve regeneration where effective Wallerian degeneration removes myelin and extracellular proteoglycans slowly. We repaired transected common peroneal (CP) nerve in rats and either elevated cAMP in the axotomized neurons by subcutaneous rolipram, a specific inhibitor of phosphodiesterase IV, and/or promoted degradation of proteoglycans in the distal nerve stump by local ChABC administration. Rolipram treatment significantly increased the number of motoneurons that regenerated axons across the repair site at 1 and 2 weeks, and increased the number of sensory neurons that regenerated axons across the repair site at 2 weeks. Local application of ChABC had a similar effect to rolipram treatment in promoting motor axon regeneration, the effect being no greater when rolipram and ChABC were administered simultaneously. We conclude that blocking inhibitors of axon regeneration by elevating cAMP or degrading proteoglycans in the distal nerve stump promotes peripheral axon regeneration after surgical repair of a transected nerve. It is likely that elevated cAMP is sufficient to encourage axon outgrowth despite the inhibitory growth environment such that simultaneous enzymatic proteoglycan degradation does not promote more axon regeneration than either elevated cAMP or proteoglycan degradation alone.     

Therapeutic time window for the application of chondroitinase ABC after spinal cord injury

Rats with a crush in the dorsal funiculi of the C4 segment of the spinal cord were treated with chondroitinase ABC delivered to the lateral ventricle, receiving 6 intraventricular injections on alternate days. In order to investigate the time window of efficacy of chondroitinase, treatment was begun at the time of injury or after a 2, 4 or 7 days delay. Behavioural testing over 6 weeks showed that acutely treated animals showed improved skilled forelimb reaching compared to penicillinase controls. Forelimb contact placing recovered in treated animals but not controls, and gait analysis showed recovery towards normal forelimb stride length in treated animals but not controls. Chondroitinase-treated animals showed greater axon regeneration than controls. The treatment effect on contact placing, stride length and axon regeneration was not dependent on the timing of the start of treatment, but in skilled paw reaching acutely treated animals recovered better function. The area of chondroitinase ABC digestion visualized by stub antibody staining included widespread digestion around the lateral ventricles and partial digestion of cervical spinal cord white matter, but not grey matter.     

Miconazole enhances nerve regeneration and functional recovery after sciatic nerve crush injury

Introduction: Improving axonal outgrowth and remyelination is crucial for peripheral nerve regeneration. Miconazole appears to enhance remyelination in the central nervous system. In this study we assess the effect of miconazole on axonal regeneration using a sciatic nerve crush injury model in rats. Methods: Fifty Sprague‐Dawley rats were divided into control and miconazole groups. Nerve regeneration and myelination were determined using histological and electrophysiological assessment. Evaluation of sensory and motor recovery was performed using the pinprick assay and sciatic functional index. The Cell Counting Kit‐8 assay and Western blotting were used to assess the proliferation and neurotrophic expression of RSC 96 Schwann cells. Results: Miconazole promoted axonal regrowth, increased myelinated nerve fibers, improved sensory recovery and walking behavior, enhanced stimulated amplitude and nerve conduction velocity, and elevated proliferation and neurotrophic expression of RSC 96 Schwann cells. Discussion: Miconazole was beneficial for nerve regeneration and functional recovery after peripheral nerve injury. Muscle Nerve 57 : 821–828, 2018     

Ursolic acid induces neural regeneration after sciatic nerve injury

In this study,we aimed to explore the role of ursolic acid in the neural regeneration of the injured sciatic nerve.BALB/c mice were used to establish models of sciatic nerve injury through unilateral sciatic nerve complete transection and microscopic anastomosis at 0.5 cm below the ischial tuberosity.The successfully generated model mice were treated with 10,5,or 2.5 mg/kg ursolic acid via intraperitoneal injection.Enzyme-linked immunosorbent assay results showed that serum S100 protein expression level gradually increased at 1-4 weeks after sciatic nerve injury,and significantly decreased at 8 weeks.As such,ursolic acid has the capacity to significantly increase S100 protein expression levels.Real-time quantitative PCR showed that S100 mRNA expression in the L4-6 segments on the injury side was increased after ursolic acid treatment.In addition,the muscular mass index in the soleus muscle was also increased in mice treated with ursolic acid.Toluidine blue staining revealed that the quantity and average diameter of myelinated nerve fibers in the injured sciatic nerve were significantly increased after treatment with ursolic acid.10 and 5 mg/kg of ursolic acid produced stronger effects than 2.5 mg/kg of ursolic acid.Our findings indicate that ursolic acid can dose-dependently increase S100 expression and promote neural regeneration in BALB/c mice following sciatic nerve injury.     

Chondroitinase ABC improves recovery of long sciatic nerve defects

Sciatic nerves from allogeneic Sprague-Dawley rats were pretreated with chondroitinase ABC and were used to bridge damaged sciatic nerves in Wistar rats. Chondroitin sulfate proteoglycans were removed from the chemically extracted acellular nerves. At 3 months after grafting, the footplate pinch test result was positive in the Wistar rats. Autotomy scores decreased, and increased muscular contraction tension appeared when triceps surae muscles were stimulated. In addition, the recovery rate of wet triceps surae muscle weight increased, and the distal segment of the chondroitinase ABC-treated graft exhibited Schwann cells next to the nerve fibers. These results suggested that chondroitinase ABC pretreatment enhanced repair of long nerve defects via acellular nerve grafting.     

维拉帕米与神经生长因子促进大鼠坐骨神经再生的协同作用

背景：实验证明周围神经损伤时,轴突的变性与神经元凋亡都与Ca2+的超载有着极其密切的关系。 目的：利用大鼠坐骨神经损伤模型观察L型钙离子通道阻滞剂维拉帕米联合神经生长因子促进周围神经再生的协同作用。 设计、时间及地点：随机对照动物实验,于2007-04/2008-11在辽宁医学院手外科实验室完成。 材料：同系健康雄性SD大鼠32只,体质量220~260 g;维拉帕米为辽宁卫星制药厂产品,国药准字H21022847;神经生长因子为sigma公司产品。 方法：同系SD大鼠32只随机分为4组,每组8只,分别在右侧梨状肌下缘5 mm切断坐骨神经后立即原位缝合造成坐骨神经损伤模型。①维拉帕米+神经生长因子组：腹腔注射维拉帕米4 mg/(kg•d),术侧腓肠肌肉注射神经生长因子0.6 μg/d。②维拉帕米组：腹腔注射维拉帕米4 mg/(kg•d),术侧腓肠肌注射等量生理盐水。③神经生长因子组：术侧腓肠肌注神经生长因子0.6 μg/d,并腹腔注射等量生理盐水。④空白对照组：分别腹腔,肌注等量生理盐水。以左侧坐骨神经为正常对照。 主要观察指标：术后12周对各组再生神经进行大体观察,神经电生理测定,组织学观察及有髓神经纤维计数。 结果：术后12周,维拉帕米+神经生长因子组足部溃疡的出现与愈合以及展抓反射出现的时间均早于其他各组。神经传导速度恢复率和有髓神经纤维计数恢复率分析表明：维拉帕米+神经生长因子组>维拉帕米组>神经生长因子组>空白对照组。光镜和电镜下可见：维拉帕米+神经生长因子组再生的神经纤维最多,轴突较为粗大。有髓神经纤维多,髓鞘完整,优于其他3组。神经纤维直径恢复率分析表明：维拉帕米+神经生长因子组>神经生长因子组>维拉帕米组>空白对照组。 结论：维拉帕米与神经生长因子对促进周围神经形态结构和功能的恢复均具有明显的协同作用。     

Specific and nonspecific regeneration of motor axons after sciatic nerve injury and repair in the rat

The pattern of motor axon regeneration following unilateral sciatic nerve lesions (freezing or transection) was studied in adult rats. Transected nerves were repaired with epineurial or fascicular sutures. Four months after the lesion, the motor neuron cell body localization in the spinal cord of plantar or common peroneal nerve axons were examined bilaterally with retrograde transport of horseradish peroxidase. Motor neuron cell body localization was similar bilaterally after freezing, indicating that regenerating axons had reached their original peripheral innervation territory. However, after nerve transection, irrespective of whether epineurial or fascicular sutures were used, motor neuron cell body distribution on the operated side was abnormal with numerous labeled cell bodies located outside the area of the normal motor neuron pool. This finding indicates that after nerve transection the normal pattern of motor axon innervation is not restored even after fascicular nerve repair.     

Valproic acid enhances axonal regeneration and recovery of motor function after sciatic nerve axotomy in adult rats

It has recently been demonstrated that valproic acid (VPA) robustly promotes neurite outgrowth, activates the extracellular signal regulated kinase pathway, and increases growth cone-associated protein 43 and bcl-2 levels in cultured human neuroblastoma SH-SY5Y cells. We hypothesized that VPA could also enhance peripheral nerve regeneration in adult animals. To test this hypothesis, we examined the effects of VPA (300 mg/kg daily for 16 weeks) on sciatic axonal regeneration following single or conditional axotomies in rats. The results showed that in VPA-treated rats there was a significant increase in the total numbers of regenerated myelinated nerve fibers and reinnervated muscle fibers in comparison with those rats not treated with VPA. As measured by sciatic function index and toe spread index, the motor function of the reinnervated hind limbs of rats receiving single axotomy without VPA treatment significantly improved at week 8 and reached plateau levels at about week 11, whereas the motor function of the reinnervated hind limbs of rats receiving single axotomy plus VPA and rats receiving conditional axotomy with or without VPA treatment significantly improved at week 4 and reached plateau levels at about week 8; there was no significant difference of the motor function among the three later groups. The results demonstrated that VPA is able to enhance sciatic nerve regeneration and recovery of motor function in adult rats, suggesting the potential clinical application of VPA for the treatment of peripheral nerve injury in humans.     

Success of regeneration of peripheral nerve axons in rats after injury at different postnatal ages

Electrophysiological experiment have been carried out on rats to see if the age at which a peripheral nerve injury occurs influences the success of regeneration. The assessment was made on the basis of two measures of peripheral nerve regeneration; the extent to which axons manage to grow across the injury site and into the distal stump, and their ability to resupply cutaneous structures with functional endings. Regeneration after nerve transection of both myelinated and unmyelinated axons was studied. The results showed that, apart from rats injured when 2 weeks old, the age at which injury occurred, over the range 4–40 weeks, had little bearing on the overall success of skin reinnervation. The 2-week-old rats showed significantly poorer recovery.