The permissive effect of cortical steroids on the induction of brain ornithine decarboxylase by nerve growth factor

The intraventricular administration of nerve growth factor causes a marked increase in the activity of ornithine decarboxylase in rat brain. This increase is much smaller in adrenalectomized rats. Dexamethasone and corticosterone, administered either systemically or intraventricularly, are able to restore the ability of nerve growth factor to induce ornithine decarboxylase. The steroids must be given at least three hours before the nerve growth factor to be fully effective.     

Facial Nerve Axotomy in Mice: A Model to Study Motoneuron Response to Injury

The goal of this surgical protocol is to expose the facial nerve, which innervates the facial musculature, at its exit from the stylomastoid foramen and either cut or crush it to induce peripheral nerve injury. Advantages of this surgery are its simplicity, high reproducibility, and the lack of effect on vital functions or mobility from the subsequent facial paralysis, thus resulting in a relatively mild surgical outcome compared to other nerve injury models. A major advantage of using a cranial nerve injury model is that the motoneurons reside in a relatively homogenous population in the facial motor nucleus in the pons, simplifying the study of the motoneuron cell bodies. Because of the symmetrical nature of facial nerve innervation and the lack of crosstalk between the facial motor nuclei, the operation can be performed unilaterally with the unaxotomized side serving as a paired internal control. A variety of analyses can be performed postoperatively to assess the physiologic response, details of which are beyond the scope of this article. For example, recovery of muscle function can serve as a behavioral marker for reinnervation, or the motoneurons can be quantified to measure cell survival. Additionally, the motoneurons can be accurately captured using laser microdissection for molecular analysis. Because the facial nerve axotomy is minimally invasive and well tolerated, it can be utilized on a wide variety of genetically modified mice. Also, this surgery model can be used to analyze the effectiveness of peripheral nerve injury treatments. Facial nerve injury provides a means for investigating not only motoneurons, but also the responses of the central and peripheral glial microenvironment, immune system, and target musculature. The facial nerve injury model is a widely accepted peripheral nerve injury model that serves as a powerful tool for studying nerve injury and regeneration.     

Use of spider silk fibres as an innovative material in a biocompatible artificial nerve conduit

Defects of peripheral nerves still represent a challenge for surgical nerve reconstruction. Recent studies concentrated on replacement by artificial nerve conduits from different synthetic or biological materials. In our study, we describe for the first time the use of spider silk fibres as a new material in nerve tissue engineering. Schwann cells (SC) were cultivated on spider silk fibres. Cells adhered quickly on the fibres compared to polydioxanone monofilaments (PDS). SC survival and proliferation was normal in Live/Dead assays. The silk fibres were ensheathed completely with cells. We developed composite nerve grafts of acellularized veins, spider silk fibres and SC diluted in matrigel. These artificial nerve grafts could be cultivated in vitro for one week. Histological analysis showed that the cells were vital and formed distinct columns along the silk fibres. In conclusion, our results show that artificial nerve grafts can be constructed successfully from spider silk, acellularized veins and SC mixed with matrigel.     

对比分析超声引导下椎旁神经阻滞与肋间神经阻滞在脊柱手术患者应用效果及对血流动力学的影响

摘要 目的：对比分析超声引导下椎旁神经阻滞与肋间神经阻滞在脊柱手术患者应用效果及对血流动力学的影响。方法：选择西安交通大学第一附属医院2020年6月至2021年12月收治的脊柱骨折患者96例作为研究对象,根据1:1随机数字表法把患者分为椎旁神经阻滞组与肋间神经阻滞组各48例。所有患者均给予脊柱手术治疗,所有手术操作都由同一组医生完成,椎旁神经阻滞组与肋间神经阻滞组分别给予超声引导下椎旁神经阻滞与肋间神经阻滞,记录两组阻滞效果及对血流动力学的影响。结果：两组通气5 min、通气30 min、恢复双肺通气30 min等时间点的HR、SPO₂值在组内与组间对比无差异（P>0.05）。两组的术中补液量、术中出血量、手术时间、麻醉时间、术中尿量等对比无差异（P>0.05）。椎旁神经阻滞组的坐骨神经运动神经、感觉神经阻滞持续时间都少于肋间神经阻滞组（P<0.05）,两组运动神经、感觉神经阻滞起效时间对比无差异（P>0.05）。椎旁神经阻滞组术后7 d的肺部感染、肺栓塞、呼吸衰竭等肺部并发症发生率2.1 %,低于肋间神经阻滞组的16.7 %（P<0.05）。结论：相对于肋间神经阻滞,超声引导下椎旁神经阻滞在脊柱手术患者并不会影响患者的血流动力学状况,也不会影响手术与麻醉过程,还可缩短坐骨神经运动神经、感觉神经阻滞持续时间,减少术后并发症的发生。     

Treatment of Combined Injuries of the Axillary and Suprascapular Nerves with Scapulothoracic Dissociation

A 20-year-old man suffered the combined axillary and suprascapular nerve palsies associated with scapulothoracic dissociation by motorcycle accident. The dislocated shoulder girdle was reduced and stabilized with osteosynthesis of the fractured clavicle and reattachment of the trapezius avulsed from the scapular spine for removal of continuous traction force to these damaged nerves. Because of no evidence of recovery on manual muscle test and electromyogram, exploration for these nerves was administered 6 weeks after injury. Although neurolysis of both nerves revealed neural continuity, excessive tension still existed on the suprascapular nerve. It was thought that previous operation in which the shoulder girdle had been reduced and stabilized as much as possible could not achieve complete anatomical reduction of the scapula. As an additional treatment, medial walls of the suprascapular and spinoglenoid notches were shaven to relax the suprascapular nerve. After a year, complete recovery of both the axillary and suprascapular nerve was identified. Although scapulothoracic dissociation is commonly recognized as massive injury of the shoulder girdle with poor prognosis because of existence of accompanied severe neurovascular injuries, there are more than a few cases in which partial damage on the infraclavicular brachial plexus is only accompanied. In case of them, there is the possibility of lesions in continuity of the nerves in which good prognosis might be expected with surgical intervention including early reduction of the shoulder girdle for removal of excessive tension to the damaged nerve.     

Predictive Outcome Modeling of Preoperative Clinical Symptoms and Electrodiagnostic Data in Tarsal Tunnel Surgery

Background  The relationship between tarsal tunnel syndrome (TTS), electrodiagnostic (Edx) findings, and surgical outcome is unknown. Analysis of TTS surgical release outcome patient satisfaction and comparison to Edx nerve conduction studies (NCSs) is important to improve outcome prediction when deciding who would benefit from TTS release. Methods  Retrospective study of 90 patients over 7 years that had tarsal tunnel (TT) release surgery with outcome rating and preoperative tibial NCS. Overall, 64 patients met study inclusion criteria with enough NCS data to be classified into one of the following three groups: (1) probable TTS, (2) peripheral polyneuropathy, or (3) normal. Most patients had preoperative clinical provocative testing including diagnostic tibial nerve injection, tibial Phalen''s sign, and/or Tinel''s sign and complaints of plantar tibial neuropathic symptoms. Outcome measure was percentage of patient improvement report at surgical follow-up visit. Results  Patient-reported improvement was 92% in the probable TTS group ( n  = 41) and 77% of the non-TTS group ( n  = 23). Multivariate modeling revealed that three out of eight variables predicted improvement from surgical release, NCS consistent with TTS ( p  = 0.04), neuropathic symptoms ( p  = 0.045), and absent Phalen''s test ( p  = 0.001). The R ² was 0.21 which is a robust result for this outcome measurement process. Conclusion  The best predictors of improvement in patients with TTS release were found in patients that had preoperative Edx evidence of tibial neuropathy in the TT and tibial nerve plantar symptoms. Determining what factors predict surgical outcome will require prospective evaluation and evaluation of patients with other nonsurgical modalities.     

视觉假体的研究进展与面临的挑战

人工视觉假体是当今国际上对视网膜色素变性和老年性黄斑病变患者进行视觉修复的研究热点,该人工装置采集外界图像信息,并进行编码处理,通过微电流刺激器将刺激微电流信号加载到微电极阵列,对视觉神经系统进行作用,从而在视觉中枢产生光幻视,实现视觉功能修复。根据目前的国际研究现状,视觉假体可以对视觉通路的任意位置进行电刺激,以期产生视光感。按照植入位置的不同,视觉假体基本上可以分为视皮层假体、视网膜上假体、视网膜下假体和视神经假体。本文着重介绍了中国的C-Sight小组在视神经假体方面的工作进展和面临的挑战。     

Internal Neurolysis in Treatment of Traumatic Peripheral Nerve Lesions

Many peripheral nerve injuries are of a contusing type with resultant intraneural scarring which causes neurologic deficit even though the nerve is still in continuity. Internal neurolysis can relieve pain and restore neurologic function in such lesions. It is important that such lesions be recognized early, fully evaluated and carefully followed so that surgical intervention can be carried out before permanent changes can develop in the denervated muscles, joints and skin. The procedure is frequently rewarded with prompt and gratifying results. The risk is minimal and the patient need spend only a short time in hospital.     

Time Course and Characteristics of the Capacity of Sensory Nerves to Reinnervate Skin Territories outside Their Normal Innervation Zones

Factors involved in the outcome of regeneration of the saphenous nerve after a cut or crush lesion were studied in adult rats with electrophysiological recordings of low-threshold mechanoreceptor activity and plasma extravasation of Evans blue after electrical nerve stimulation that activated C fibers.

In the first series of experiments, saphenous and sciatic nerve section was combined with anastomosis of the transected proximal end of the saphenous nerve to the distal end of the cut tibial nerve. Regeneration of saphenous nerve fibers involved in plasma extravasation and low-threshold mechanoreceptor activity in the glabrous skin was observed 13 weeks after nerve anastomosis. Substance P-, calcitonin gene-related peptide-, and protein gene product 9.5 (PGP-9.5)-immunoreactive (IR) thin epidermal and dermal nerve endings, as well as coarse dermal PGP-9.5-IR nerve fibers and Meissner corpuscles and Merkel cell-neurite-like complexes, were observed in the reinnervated glabrous skin at this time.

In a second series of experiments, the time course of the regeneration of saphenous nerve axons to the permanently sciatic-nerve-denervated foot sole was examined. Saphenous-nerve-induced plasma extravasation and low-threshold mechanoreceptor activity in the saphenous nerve were found in the normal saphenous nerve territory 2, 3, 4, and 6 weeks after sciatic nerve cut combined with saphenous nerve crush in the left hindlimb. Saphenous-nerve-induced plasma extravasation was also present in the glabrous skin normally innervated by the sciatic nerve 3, 4, and 6 weeks after the sciatic cut/saphenous crush lesion. However, no low-threshold mechanoreceptor activity was detected in the saphenous nerve when the glabrous skin area was stimulated.

In a third series of experiments, the fate of the expansion of the saphenous nerve territory after saphenous nerve crush was examined when the crushed sciatic nerve had been allowed to regenerate. Nerve fibers involved in plasma extravasation were observed in the glabrous skin of the hindpaw after saphenous nerve, as well as after tibial nerve, C-fiber stimulation 3, 12, and 43 weeks after the saphenous crush/sciatic crush lesion.

Low-threshold mechanoreceptors from the regenerated saphenous nerve, which primarily innervates hairy skin, seem to be functional in the glabrous skin if the axons are guided by the transected tibial nerve by anastomosis. Furthermore, the results indicate that fibers from the regenerating saphenous nerve that have extended into denervated glabrous skin areas can exist even if sciatic nerve axons are allowed to grow back to their original territory.     

Inhibition of Rho kinase (ROCK) increases neurite outgrowth on chondroitin sulphate proteoglycan in vitro and axonal regeneration in the adult optic nerve in vivo

Inhibitory molecules derived from CNS myelin and glial scar tissue are major causes for insufficient functional regeneration in the mammalian CNS. A multitude of these molecules signal through the Rho/Rho kinase (ROCK) pathway. We evaluated three inhibitors of ROCK, Y- 27632, Fasudil (HA-1077), and Dimethylfasudil (H-1152), in models of neurite outgrowth in vitro. We show, that all three ROCK inhibitors partially restore neurite outgrowth of Ntera-2 neurons on the inhibitory chondroitin sulphate proteoglycan substrate. In the rat optic nerve crush model Y-27632 dose-dependently increased regeneration of retinal ganglion cell axons in vivo. Application of Dimethylfasudil showed a trend towards increased axonal regeneration in an intermediate concentration. We demonstrate that inhibition of ROCK can be an effective therapeutic approach to increase regeneration of CNS neurons. The selection of a suitable inhibitor with a broad therapeutic window, however, is crucial in order to minimize unwanted side effects and to avoid deleterious effects on nerve fiber growth.     

鱼类动眼神经的形态学研究

目的：应用生物胞素法观察罗非鱼动眼神经的形态分布。方法：本实验用罗非鱼,10只（性别不限）,体长12．16cm,动物浸入140mg／L三卡因间氨苯酸乙脂甲磺酸盐{tricainemethanesulfonate（MS222）}溶液中麻醉,在手术显微镜下暴露动眼神经,通过生物胞素（Biocytin）结晶追踪技术研究定位硬骨鱼类动眼神经的形态分布。结果：①被标记的神经纤维长而粗细不等,排列比较松散,从后外向前内方向行走,逐渐靠近,终于位于中脑腹侧部的动眼神经核细胞,同时可以观察到有些神经纤维交叉到对侧。②神经核细胞呈圆形和卵圆形,大小不一,亦可见神经元的突起,有的突起呈螺旋状连于胞体,有的呈线状连于胞体,形成神经终末及突触联系,并可见到多极神经元,并在神经纤维之中也可以见到少数神经核细胞,但部分标记结构并不太完整,有些标记的神经细胞和神经纤维不是很清楚。结论：鱼类动眼神经纤维在中脑内的走行与其他动物基本一致,动眼神经核位于中脑水管腹侧部。     

鱼类滑车神经的形态学研究

目的：应用生物胞素法观察罗非鱼滑车神经的形态分布。方法：本实验用罗非鱼,10只（性别不限）,体长12～16cm,动物浸入140mg／L三卡因间氨苯酸乙脂甲磺酸盐{tricainemethanesulfonate（MS222）}溶液中麻醉,在手术显微镜下暴露滑车神经,通过生物胞素（Biocytin）结晶追踪技术研究定位硬骨鱼类滑车神经的形态分布。结果：①被标记的神经纤维长而粗细不等,平行致密排列,从后外下向前内上方向行走,逐渐上行,于中脑水管正中背侧部,进行交叉到对侧,终于中脑水管腹侧部的滑车神经核细胞。②神经核细胞呈圆形和卵圆形,大小不一,亦可见神经元的突起,有的突起呈螺旋状连于胞体,有的呈线状连于胞体,形成神经终末及突触联系,并可见到多极神经元。结论：鱼类滑车神经纤维在中脑内的走行与人类基本一致,滑车神经核位于中脑水管腹侧部。     

Nerve Transfer in Delayed Obstetrical Palsy Repair

Objective

 When root avulsions are detected in children suffering from obstetrical brachial plexus palsy (OBPP), neurotization procedures of different nerve trunks are commonly applied in primary brachial plexus repair, to connect distally the nerves of the upper limbs using healthy nerve structures. This article aims to outline our experience of neurotization procedures in OBPP, which involves nerve transfers in the event of delayed repair, when a primary repair has not occurred or has failed. In addition, we propose the opportunity for late repair, focusing on extending the time limit for nerve surgery beyond that which is usually recommended. Although, according to different authors, the time limit is still unclear, it is generally estimated that nerve repair should take place within the first months of life. In fact, microsurgical repair of OBPP is the technique of choice for young children with the condition who would otherwise have an unfavorable outcome. However, in certain cases the recovery process is not clearly defined so not all the patients are direct candidates for primary nerve surgery.

Methods

 In the period spanning January 2005 through January 2011, among a group of 105 patients suffering from OBPP, ranging from 1 month to 7 years of age, the authors have identified a group of 32 partially recovered patients. All these patients underwent selective neurotization surgery, which was performed in a period ranging from 5 months to 6.6 years of age.

Results

 Late neurotization of muscular groups achieved considerable functional recovery in these patients, who presented with reduced motor function during early childhood. The said patients, with the exception of five, would initially have avoided surgery because they had not met the criteria for nerve surgery.

Conclusion

 We have concluded that the execution of late nerve surgical procedures can be effective in children affected by OBPP.     

神经生长因子与冻干异体神经桥接大鼠神经缺损的研究

实验采用冻干处理的异体神经与外源性神经生长因子（ＮＧＦ）结合来桥接大鼠的坐骨神经１．０ｃｍ的缺损。用雄性Ｗｉｓｔａｒ大鼠进行的四组实验结果表明：冻干处理的异体神经可降低其抗原性,但处理后并不损害雪旺氏细胞（ＳＣ）基底膜的完整性,在移植后可能成为轴突再生的通道和支架;外源性ＮＧＦ与冻干神经结合形成的复合体,可为神经的再生提供一个较好的微环境,具有成为理想桥接材料的可能性     

Allatostatins in the nerves of the antennal pulsatile organ muscle of the cockroach Diploptera punctata.

The presence of allatostatins in the nerves of the antennal pulsatile organ muscle of the cockroach Diploptera punctata was confirmed by immunocytochemistry, bioassay, and HPLC. Immunocytochemical reactivity with monoclonal antibody against allatostatin I showed strong allatostatin immunoreactivity in the antennal heart nerve which innervates this muscle with varicosities along the muscle fibers and in the insertion of the muscle on the pulsatile ampullae. Bioassay of Sep-Pak purified muscle extract demonstrated inhibition of juvenile hormone synthesis by corpora allata in vitro. A dose-response curve showed maximum inhibition of juvenile hormone synthesis was achieved with 10-20 pulsatile organ muscle eq/corpora allata, and 50% inhibition achieved with an estimated 2.6 pulsatile organ muscle eq. Two successive HPLC separations of the Sep-Pak purified extract yielded bioactive fractions corresponding to the elution times of the five known allatostatins.     

Long-term changes in neurotrophic factor expression in distal nerve stump following denervation and reinnervation with motor or sensory nerve

Several factors have been proposed to account for poor motor recovery after prolonged denervation, including motor neuron cell death and incomplete or poor regeneration of motor fibers into the muscle. Both may result from failure of the muscle and the distal motor nerve stump to continue expression of neurotrophic factors following delayed muscle reinnervation. This study investigated whether regenerating motor or sensory axons modulate distal nerve neurotrophic factor expression. We found that transected distal tibial nerve up-regulated brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) mRNA, down-regulated neurotrophin-3 and ciliary neurotrophic factor mRNA, and that although these levels returned to normal with regeneration, the chronically denervated distal nerve stump continued to express these neurotrophic factors for at least 6 months following injury. A sensory nerve (the cutaneous saphenous nerve) sutured to distal tibial nerve lowered injury-induced BDNF and GDNF mRNA levels in distal stump, but repair with a mixed nerve (peroneal, containing muscle and cutaneous axons) was more effective. Repair with sensory or mixed nerves did not affect nerve growth factor or neurotrophin-3 expression. Thus, distal nerve contributed to a neurotrophic environment for nerve regeneration for at least 6 months, and sensory nerve repair helped normalize distal nerve neurotrophic factor mRNA expression following denervation. Furthermore, as BDNF and GDNF levels in distal stump increased following denervation and returned to control levels following reinnervation, their levels serve as markers for the status of regeneration by either motor or sensory nerve.     

阴部神经痛的解剖学基础及治疗进展

阴部神经痛是发生于会阴部阴部神经支配区域的烧灼样,电击样,针刺样疼痛,是典型的神经病理性疼痛,其目前的患病率尚未准确统计、诊断和治疗均比较困难,患者长期遭受精神和身体上的双重折磨、生活质量低下。阴部神经常与阴部血管伴行共同走行于阴部神经管内,可分为三个主要的分支,即直肠下神经,会阴神经和阴茎/阴蒂背神经。不同分支病变将会导致不同部位的疼痛。其治疗方法目前主要包括保守治疗、阴部神经阻滞、阴部神经外科减压以及神经调控。本文就阴部神经解剖结构,阴部神经痛病因和临床表现,诊断及其治疗进展做一简要综述。     

甲状腺术中喉返神经显露对暂时性喉返神经损伤发生率的影响

目的:探究甲状腺术中喉返神经显露对暂时性喉返神经损伤发生率的影响。方法:选择我院2016年10月-2018年10月收治的行甲状腺切除术的115例患者为研究对象,按照其入院顺序经随机数字表法分为两组,两组患者均行常规甲状腺切除术。其中,对照组58例患者未显露喉返神经;研究组57例患者常规显露喉返神经,记录并比较两组患者的手术时间、术中出血量、术后引流量、切口长度和住院时间等围术期手术指标,术后1d、4d、7d的甲状旁腺激素(PTH)水平、钙离子(Ca2+)水平,术后暂时性喉返神经损伤、术后声音嘶哑、低钙血症等并发症的发生情况。结果:研究组患者的手术时间、术中出血量、术后引流量均短于(少于)对照组(P0.05),但两组患者的切口长度和住院时间无显著性差异(P0.05);研究组患者术后1d、4d、7d的血清PTH、Ca2+水平均高于对照组(P0.05),暂时性喉返神经损伤、术后声音嘶哑、低钙血症发生率均低于对照组(P0.05)。结论:甲状腺术中喉返神经显露可有效预防暂时性喉返神经和甲状腺功能的损伤,降低术后并发症的发生率,且患者的围术期指标均显著改善。     

Drug-delivering nerve conduit improves regeneration in a critical-sized gap

Autologous nerve grafts are the current “gold standard” for repairing large nerve gaps. However, they cause morbidity at the donor nerve site and only a limited amount of nerve can be harvested. Nerve conduits are a promising alternative to autografts and can act as guidance cues for the regenerating axons, without the need to harvest donor nerve. Separately, it has been shown that localized delivery of GDNF can enhance axon growth and motor recovery. FK506, an FDA approved small molecule, has also been shown to enhance peripheral nerve regeneration. This paper describes the design of a novel hole-based drug delivery apparatus integrated with a polytetrafluoroethylene (PTFE) nerve conduit for controlled local delivery of a protein such as GDNF or a small molecule such as FK506. The PTFE devices were tested in a diffusion chamber, and the bioactivity of the released media was evaluated by measuring neurite growth of dorsal root ganglions (DRGs) exposed to the released drugs. The drug delivering nerve guide was able to release bioactive concentrations of FK506 or GDNF. Following these tests, optimized drug releasing nerve conduits were implanted across 10 mm sciatic nerve gaps in a BL6 yellow fluorescent protein (YFP) mouse model, where they demonstrated significant improvement in muscle mass, compound muscle action potential, and axon myelination in vivo as compared with nerve conduits without the drug. The drug delivery nerve guide could release drug for extended periods of time and enhance axon growth in vitro and in vivo.     

Activity cage as a method to analyze functional recovery after sciatic nerve injury in mice

The aim of this paper is to show the activity cage as a viable method for tracking functional nerve recovery. The activity cage measures spontaneous coordinate activity, meaning movement in either the horizontal or vertical plane, of experimental animals within a specified amount of time. This uses a minimum of researcher time conducting functional testing to determine functional recovery of the nerve. Using microsurgical forceps, a crush injury was inflicted unilaterally, on the left side, upon the 4-month-old C3H mice creating a very high degree of pressure for 6 s upon the exposed sciatic nerve. The locomotion function of the mice was evaluated using the activity cage preoperatively, 1, 7, 14, 21, and 28 days after the surgical procedure. We found that using the activity cage functional recovery occurred by 14 days after nerve crush injury. It was also shown that, coinciding with functional recovery, immunohistochemistry changes for GD1a and nNOS appeared at the level of L4, where the sciatic nerve joins the spinal column. GD1a and nNOS have both been linked to regenerative processes in mammalian nervous systems.