神经生长因子与周围神经病变相关性研究进展

神经生长因子（nerve growth factor,NGF）是目前研究最为清楚的一种神经营养因子（NTFs）,具有营养、保护神经元及促进受损神经的再生和修复等多种生物学功能。研究表明NGF对周围神经系统的神经再生、生长发育、血管生成和轴突形成具有重要作用,提示NGF可应用于周围神经再生和修复。现将NGF对周围神经病变的作用机制和特点综述如下。     

糖尿病周围神经病与神经生长因子

周围神经病累及的感觉神经元和交感神经元是神经生长因子在外周神经系统营养、支持的主要神经元。动物实验和临床检测表明，糖尿病周围神经病时体内神经生长因子水平及功能下降，提示内源性神经生长因子与周围神经病的某些病理改变和临床症状密切相关。应用外源性神经生长因子能有助于周围神经病变的减轻和恢复。     

亚急性脊髓联合变性16例临床分析

亚急性脊髓联合变性(SCD)是由维生素B12缺乏引起的神经系统变性疾病，病变主要累及脊髓后索、侧索及周围神经。临床表现为双下肢深感觉缺失、感觉性共济失调、痉挛性截瘫及周围神经病变。近年来，由于各种辅助检查在临床中的广泛应用，对此病有了较多的认识，现将我院1999～2002年收治的16例SCD分析报道如下．     

周围神经损伤与再生的研究进展

周围神经损伤在临床上很常见,严重影响患者生存质量,尽管显微外科技术有了很大的进步,但是修复的结果还不能令人满意,目前有应用人工组织技术和转基因的方法来修复周围神经损伤的报道,但达到临床广泛应用仍需付出极大努力。周围神经损伤的修复是目前尚未完全解决的问题。下面对周围神经损伤与再生的研究进展作一综述。1周围神经损伤的分类和病理生理过程     

周围神经卡压综合征的外科治疗

周围神经卡压性疾病是最为常见的周围神经系统疾病,也是很多周围神经系统疾病发生发展的影响因素.周围神经卡压性疾病涉及的周围神经繁多,临床表现各异,鉴别诊断困难,治疗上涉及多学科合作,部分患者疗效不理想.积极开展周围神经外科亚专科建设有助于提高周围神经卡压性疾病的诊疗质量.     

白细胞介素-1(IL-1)对周围神经再生及功能恢复的实验研究

目的：本研究采用神经再生室研究IL－1（Interleukin-1）对周围神经再生功能的影响。方法：将57只SD大白鼠随机分为IL－1、IL－ra（Interfeukin－1ReceptorAntagonist）和等渗盐水三组。术后3、6周取材作神经电生理检查，术后16周作大鼠趾展宽度测定。结果：IL－1组再生周围神经功能明显优于IL－ra组和等渗盐水组。IL－ra组和等渗盐水组间没有明显差异。结论：IL-1具有促进周围神经再生及神经功能恢复的作用．     

长期饮酒者的自主及周围神经病变──酒精毒性作用的量效关系

长期饮酒者的自主及周围神经病变──酒精毒性作用的量效关系吕志勤编译张青校（交通部北京交通医院）长期饮酒对全身组织可以产生广泛的影响，其中包括自主神经和周围神经系统。但长期饮酒导致自主和周围神经系统的流行病机理至今尚不清楚，推测与营养状况、含酒精饮料的...     

48例糖尿病周围神经病的电生理检查分析

糖尿病因代谢障碍和血管改变使神经系统受损，特别是周围神经受累，四肢较为明显，无论是出现临床症状或未出现临床症状，运动感觉神经传导速度均可改变，所以电生理测定对糖尿病性周围神经病的早期诊断具有重要价值。     

低强度超声促进周围神经修复的研究进展

周围神经损伤后的修复一直是医学界研究的热点和难点。虽然显微外科学的发展以及组织工程的出现,为周围神经损伤后的修复带来了佳音,但是目前其临床疗效仍不十分理想。低强度超声波作为物理治疗的一种方式,被研究认为能促进周围神经损伤的修复。低强度超声主要利用超声波的机械效应,提高细胞膜和细胞壁的通透性,增强细胞的新陈代谢,促进细胞生长。低强度超声治疗最早在临床上主要应用于促进骨折愈合、肌腱愈合及软骨、椎间盘等组织的愈合中。早期人们也研究过低强度超声在神经系统中的作用,争论的焦点主要在连续超声或脉冲超声方式的选择以及热效应是否发挥作用上。初步研究表明:低强度超声可以促进雪旺细胞增生以及在大鼠坐骨神经挤压伤、坐骨神经截断伤、神经导管修复缺损坐骨神经等神经损伤过程中的修复和再生。对于其作用的机制的研究也从细胞学、分子生物学、酶学、离子通道等多个角度进行了探索。作为无创便捷的治疗方法,低强度超声虽然还有很多方面的问题尚待商榷研究,其未来广阔的临床应用空间是值得肯定和期待的。     

干燥综合征的神经系统损害

目的 观察干燥综合征的神经系统损害及临床特征。方法分析干燥综合征合并神经系统损害的临床特征及病变部位。结果9例干燥综合征合并神经系统损害的患者中，周围神经损害7例，中枢神经损害2例。结论干燥综合征合并神经系统损害以周围神经病变为主，其神经系统症状可出现在干燥综合征诊断之前，早期治疗可改善干燥综合征的神经系统损害症状。     

外周神经损伤后再生的相关信号通路

由于神经元损伤后的自身再修复能力有限,临床上对于神经损伤一直缺乏有效的治疗手段,因此,寻找促进神经损伤后修复的药物,以及探索其相关作用机制始终是神经科学领域的研究热点.有研究表明,在外周神经组织中,神经元细胞和雪旺细胞内的信号通路对于外周神经损伤后再生有着重要作用.本文综述了雪旺细胞和神经元内与外周神经再生相关的信号通...     

Effects of melatonin on peripheral nerve regeneration

In the available literature, there are thousands of studies on peripheral nerve regeneration using many nerves of several animals at different ages with various types of lesions and different methods of evaluation at certain time of follow-up. Despite many experimental data and clinical observations, there is still no ideal treatment method enhancing peripheral nerve regeneration. In clinical practice, various types of surgical nerve repair techniques do not frequently result in complete recovery due to neuroma formation, lipid peroxidative damage, ischemia and other factors. Recently, a number of neuroscientists demonstrated that pineal neurohormone melatonin (MLT) has an effect on the morphologic features of the nerve tissue, suggesting its neuroprotective, free radical scavenging, antioxidative, and analgesic effects in degenerative diseases of peripheral nerves. At present, it is widely accepted that MLT has a useful effect on axon length and sprouting after traumatic events to peripheral nerves. Our studies using various experimental injury models clearly suggest positive effects of MLT on the number of axons, thickness of myelin sheath by inhibition of collagen accumulation and neuroma formation following traumatic events to peripheral nerves, myelination of developing peripheral nerve after intrauterine ethanol exposure. Nevertheless, further experimental and randomized controlled clinical studies are vital to identify the clinical use of MLT hormone. This is an overview of recent patents and current literature in terms of the effects of MLT on peripheral nerve regeneration based on a critical analysis of electrophysiological, biochemical and light and electron microscopic findings, in addition to functional observations.     

Exosomes as a Promising Therapeutic Strategy for Peripheral Nerve Injury

Peripheral nerve injury has a high incidence and often leads to severe losses of sensory and motor functions in the afflicted limb. Autologous nerve grafts are widely accepted as the gold standard for peripheral nerve repair, but the presence of inherent drawbacks dramatically reduces their usability. Numerous tissue engineering nerve grafts are developed as alternatives to autologous nerve grafts, and a variety of cells and neurotrophic factors are introduced into these grafts for improvement. However, they are still difficult to obtain satisfactory clinical results. Peripheral nerve regeneration following injury remains a significant challenge for researchers and clinicians. Exosomes are extracellular membranous nanovesicles that are secreted by most cells. As the key players of intercellular communication, exosomes play a fundamental role in the physiological and pathological processes of the nervous system. Accumulating evidence has suggested that exosomes can exert neurotherapeutic effects via mediating axonal regrowth, Schwann cell activation, vascular regeneration, and inflammatory regulation. Exosomes are emerging as a promising approach for treating peripheral nerve injury. Furthermore, they also provide possibilities for enhancing the repairing capacity of various nerve grafts. This review primarily highlights the regenerative effects of exosomes on peripheral nerve injury. The exosomes from distinct sources reported so far in the literature are summarized to understand their roles in the process of nerve repair. Moreover, the challenges that must be addressed in their clinical transformation are outlined as well. This review also provides further insight into the potential application of exosomes for peripheral nerve repair.     

Nanofiber scaffolds facilitate functional regeneration of peripheral nerve injury

Peripheral nerve injury still remains a refractory challenge for both clinical and basic researchers. A novel nanofiber conduit made of blood vessel and filled with amphiphilic hydrogel of self-assembling nanofiber scaffold (SAPNS) was implanted to repair a 10 mm nerve gap after sciatic nerve transection. Empty blood vessel conduit was implanted serving as control. Results showed that this novel nanofiber conduit enabled the peripheral axons to regenerate across and beyond the 10 mm gap. Motoneuron protection, axonal regeneration and remyelination were significantly enhanced with SAPNS scaffold treatments. The target reinnervation and functional recovery induced by the regenerative nerve conduit suggest that SAPNS-based conduit is highly promising application in the treatment of peripheral nerve defect.From the Clinical EditorIn this paper by Zhan et al, a novel self-assembling nanofiber scaffold is reported to promote regeneration of peripheral nerves in a sciatic nerve injury model. The promising results and the obvious medical need raises hope for a clinical translation of this approach hopefully in the near future.     

The influence of drugs on peripheral nerve regeneration

Abstract

Currently, there are no established adjuvant drugs for the acceleration of peripheral nerve regeneration. In this paper, we reviewed the literature from the last 10 years and described the drugs proved to accelerate the functional and histological regeneration of the peripheral nerves, either after trauma or in neuropathy experimental models. The vast majority of the studies were experimental with very few small clinical studies, which indicates the need for prospective randomized studies to identify the best drugs to use as adjuvants for nerve regeneration.     

Therapeutic augmentation of the growth hormone axis to improve outcomes following peripheral nerve injury

Introduction: Peripheral nerve injuries often result in debilitating motor and sensory deficits. There are currently no therapeutic agents that are clinically available to enhance the regenerative process. Following surgical repair, axons often must regenerate long distances to reach and reinnervate distal targets. Progressive atrophy of denervated muscle and Schwann cells (SCs) prior to reinnervation contributes to poor outcomes. Growth hormone (GH)-based therapies have the potential to accelerate axonal regeneration while at the same time limiting atrophy of muscle and the distal regenerative pathway prior to reinnervation.

Areas covered: In this review, we discuss the potential mechanisms by which GH-based therapies act on the multiple tissue types involved in peripheral nerve regeneration to ultimately enhance outcomes, and review the pertinent mechanistic and translational studies that have been performed. We also address potential secondary benefits of GH-based therapies pertaining to improved bone, tendon and wound healing in the setting of peripheral nerve injury.

Expert opinion: GH-based therapies carry great promise for the treatment of peripheral nerve injuries, given the multi-modal mechanism of action not seen with other experimental therapies. A number of FDA-approved drugs that augment the GH axis are currently available, which may facilitate clinical translation.     

Peripheral Nerve Nanoimaging: Monitoring Treatment and Regeneration

Accidental and iatrogenic trauma are major causes of peripheral nerve injury. Healing after nerve injury is complex and often incomplete, which can lead to acute or chronic pain and functional impairment. Current assessment methods for nerve regeneration lack sensitivity and objectivity. There is a need for reliable and reproducible, noninvasive strategies with adequate spatial and temporal resolution for longitudinal evaluation of degeneration or regeneration after injury/treatment. Methods for noninvasive monitoring of the efficacy and effectiveness of neurotherapeutics in nerve regeneration or of neuropathic pain are needed to ensure adequacy and responsiveness to management, especially given the large variability in the patient populations, etiologies, and complexity of nerve injuries. Surrogate biomarkers are needed with positive predictive correlation for the dynamics and kinetics of neuroregeneration. They can provide direct real-time insight into the efficacy and mechanisms of individualized therapeutic intervention. Here, we review the state-of-the-art tools, technologies, and therapies in peripheral nerve injury and regeneration as well as provide perspectives for the future. We present compelling evidence that advancements in nanomedicine and innovation in nanotechnology such as nanotheranostics hold groundbreaking potential as paradigm shifts in noninvasive peripheral nerve imaging and drug delivery. Nanotechnology, which revolutionized molecular imaging in cancer and inflammatory disease, can be used to delineate dynamic molecular imaging signatures of neuroinflammation and neuroregeneration while simultaneously monitoring cellular or tissue response to drug therapy. We believe that current clinical successes of nanotechnology can and should be adopted and adapted to the science of peripheral nerve injury and regeneration.     

Muscle-derived stem cells: important players in peripheral nerve repair

ABSTRACT

Introduction: Stem cell therapy for peripheral nerve repair is a rapidly evolving field in regenerative medicine. Although most studies to date have investigated stem cells originating from bone marrow or adipose, skeletal muscle has recently been recognized as an abundant and easily accessible source of stem cells. Muscle-derived stem cells (MDSCs) are a diverse population of multipotent cells with pronounced antioxidant and regenerative capacity.

Areas covered: The current literature on the various roles MDSCs serve within the micro- and macro-environment of nerve injury. Furthermore, the exciting new research that is establishing MDSC-cellular therapy as an important therapeutic modality to improve peripheral nerve regeneration.

Expert opinion: MDSCs are a promising therapeutic agent for the repair of peripheral nerves; MDSCs not only undergo gliogenesis and angiogenesis, but they also orchestrate larger pro-regenerative host responses. However, the isolation, transformation, and in-vivo behavior of MDSCs require further evaluation prior to clinical application.     

Inhibitors targeting hepatocyte growth factor receptor and their potential therapeutic applications

The hepatocyte growth factor (HGF)/c-Met signaling pathway is important in mediating a wide range of biological activities, including embryological development, wound healing, tissue regeneration, angiogenesis, proliferation, survival, scattering, motility, invasion and morphogenic differentiation. HGF and/or c-Met are expressed at abnormally high levels in a large variety of solid tumors. Various c-Met mutations have been described in many solid tumors and some hematologic malignancies. Therefore, inhibition of the HGF/c-Met signaling pathway has great potential in molecular targeted cancer therapy. Many patent applications associated with inhibition of the HGF/c-Met axis have been published in the past few years. There are four small molecule c-Met inhibitors presently in clinical trials. This review focusses on recent patent applications for small molecule c-Met inhibitors and their potential applications in cancer therapy.