Nerve Regeneration

The anatomy and physiology of nerve tissue and the peripheral nerve are reviewed. The importance of the anatomical and physiological understanding of nerve tissue in the surgical repair of nerve injuries is discussed. This includes an outline of the light and electron microscopic histology of nerve and a short review of axoplasmic flow. In addition, the nerve coverings, endoneurium, perineurium, and epineurium, are described. The relationship of these coverings to the surgical therapy of nerve injuries is outlined. By maintaining, where possible, nerve fascicle continuity and by restoring, where practical, the normal physiology of distorted but not disrupted fascicles, with the use of careful internal neurolysis, optimal clinical return of function should be achieved.

For neurorehabilitation of patients with spinal cord injury (SCI), the traditional emphasis on social adaptation is being expanded to include strategies that promote plasticity and regeneration in the central nervous system. Such strategies are needed to optimize recovery of neurological function. For example, the known dependence of most cellular processes on physical activity has led to the novel concept that activity is important in neural repair. This hypothesis has given rise to activity-based restoration therapies (ABRT), which aim to optimize neural activity in the damaged spinal cord, particularly below the injury level. Here, we review the basic science and clinical evidence supporting the lifelong use of ABRT for recovery from spinal cord injury. We define and describe ABRT, and discuss its components, its clinical applications, its relationship to medical management of spinal cord injury, and the potential influences of medications on recovery. We also discuss the health ...

Glial-derived neurotrophic factor (GDNF) promotes both sensory and motor neuron survival. The delivery of GDNF to the peripheral nervous system has been shown to enhance regeneration following injury. In this study we evaluated the effect of affinity-based delivery of GDNF from a fibrin matrix in a nerve guidance conduit on nerve regeneration in a 13 mm rat sciatic nerve defect. Seven experimental groups were evaluated which received GDNF or nerve growth factor (NGF) with the delivery system within the conduit, control groups excluding one or more components of the delivery system, and nerve isografts. Nerves were harvested 6 weeks after treatment for analysis by histomorphometry and electron microscopy. The use of the delivery system (DS) with either GDNF or NGF resulted in a higher frequency of nerve regeneration vs. control groups, as evidenced by a neural structure spanning the 13 mm gap. The GDNF DS and NGF DS groups were also similar to the nerve isograft group in measures of nerve fiber density, percent neural tissue and myelinated area measurements, but not in terms of total fiber counts. In addition, both groups contained a significantly greater percentage of larger diameter fibers, with GDNF DS having the largest in comparison to all groups, suggesting more mature neural content. The delivery of GDNF via the affinity-based delivery system can enhance peripheral nerve regeneration through a silicone conduit across a critical nerve gap and offers insight into potential future alternatives to the treatment of peripheral nerve injuries.

Physical rehabilitation following spinal cord injury-related paralysis has traditionally focused on teaching compensatory techniques, thus enabling the individual to achieve day-to-day function despite significant neurological deficits. But the concept of an irreparable central nervous system (CNS) is slowly being replaced with evidence related to CNS plasticity, repair, and regeneration, all related to persistently maintaining appropriate levels of neurological activity both below and above the area where the damage occurred. It is now possible to envision functional repair of the nervous system by implementing rehabilitative interventions. Making the transition from "bench to bedside" requires careful analysis of existing basic science evidence, strategic focus of clinical research, and pragmatic implementation of new therapeutic tools. Activity, defined as both function specific motor task and exercise appears to be a necessity for optimization of functional, metabolic,...

Nerve injury is one of the most serious complications associated with limb-lengthening. We examined the risk, assessment, and treatment of nerve lesions associated with limb-lengthening. We retrospectively studied the records on 814 limb-lengthening procedures. Nerve lesions were defined by clinical signs and symptoms of motor function impairment, sensory alterations, referred pain in the distribution of an affected nerve, and/or positive results of quantitative sensory testing with use of a pressure specified sensory device. Seventy-six (9.3%) of the limbs had a nerve lesion. Eighty-four percent of the nerve lesions occurred during gradual distraction, and 16% occurred immediately following surgery. The pressure specified sensory device showed 100% sensitivity and 86% specificity in the detection of nerve injuries. The patients in whom the lesion was diagnosed with this method, or with this method as well as with nerve conduction studies, had significantly faster recovery than did ...

Peripheral nerves are complex histological structures that can be affected by a variety of conditions with different degree of axonal degeneration and demyelination. For the study of peripheral nerve regeneration in pathology and tissue engineering, it is necessary to evaluate the regeneration, remyelination and extracellular matrix reorganization of the neural tissue. Currently, different histochemical techniques must be used in parallel, and a correlation among their findings should be further performed. In this work, we describe a new histochemical method for myelin and collagen fibers based on luxol fast blue and picrosirius methods, for the evaluation of the morphology, the myelin sheath and the collagen fiber reorganization using a model of peripheral nerve regeneration. Whole brain, normal sciatic nerve and regenerating peripheral nerve samples were fixed in 10% neutral buffered formalin and paraffin-embedded, for the performance of the hematoxylin-eosin stain, the Luxol fast blue method and the new histochemical method for myelin and collagen. The results of this technique revealed that this new histochemical method allowed us to properly evaluate histological patterns, and simultaneously observe the histochemical reaction for myelin sheath and collagen fibers in normal tissue, and during the regeneration process. In conclusion, this new method combines morphological and histochemical properties that allowed us to determine with high accuracy the degree of remyelination and collagen fibers reorganization. For all these reasons, we hypothesize that this new histochemical method could be useful in pathology and tissue engineering.

Lesions in the nervous system induce rapid activation of glial cells and under certain conditions additional recruitment of granulocytes, T-cells and monocytes/macrophages from the blood stream triggered by upregulation of cell adhesion molecules, chemokines and cytokines. Hematogenous cell infiltration is not restricted to infectious or autoimmune disorders of the nervous system, but also occurs in response to cerebral ischemia and traumatic lesions. Neuroinflammation can cause neuronal damage, but also confers neuroprotection. Granulocytes occlude vessels during reperfusion after transient focal ischemia, while the functional role of T-cells and macrophages in stroke development awaits further clarification. After focal cerebral ischemia neurotoxic mediators released by microglia such as the inducible nitric oxide synthase (leading to NO synthesis) and the cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) are upregulated prior to cellular inflammat...