Peripheral Nerve Healing Research Articles

Isolation, culture, and characterization of primary endothelial cells and pericytes from mouse sciatic nerve.

The recovery of injured peripheral nerves relies on angiogenesis, where newly formed blood vessels act as pathways guiding Schwann cells across the wound to support axon regeneration. While some research has examined this process, the specific mechanisms of angiogenesis in peripheral nerve healing remain unclear. In vitro models are vital tools to investigate these mechanisms; however, no current in vitro culture methods exist for isolating vascular cells, such as endothelial cells (ECs) and pericytes, specifically from sciatic nerves. We developed a straightforward and reliable technique for isolating ECs and pericytes from injured sciatic nerves, optimized for use in in vitro studies. Cell types were characterized using specific markers and phenotypic assessments, with flow cytometry confirming cell identity and determining cell purity. Our method successfully isolated high-purity ECs and pericytes from injured sciatic nerves. Immunofluorescence analysis showed that primary cultured ECs exhibited strong positive staining for CD31, while pericytes stained strongly for NG2 and PDGFRβ. Flow cytometric analysis confirmed that ECs achieved a purity of 90.22%, and pericytes reached a purity of 92.01%. Both cell types were capable of forming organized capillary-like structures, and in co-culture systems, pericytes effectively wrapped around ECs. Current isolation methods for ECs and pericytes from sciatic nerves are limited. Although techniques exist for isolating these cells from other tissues, they often rely on enzymatic digestion, which can damage cell surface proteins and reduce cell viability. Our method allows for the efficient isolation of intact ECs and pericytes from sciatic nerve tissue without such drawbacks, providing a robust platform for in vitro studies. This newly developed method offers an effective approach to isolate ECs and pericytes from the sciatic nerve, contributing a valuable tool for investigating the function and pathology of angiogenesis in the context of sciatic nerve injury recovery.

Conductive polyphenol microneedles coupled with electroacupuncture to accelerate wound healing and alleviate depressive-like behaviors in diabetes

Inflammation and depression are serious complications of diabetes that interact to form a feedback loop and may hinder diabetic wound healing. They share a common pathophysiological basis of abnormal interactions between diabetic wounds and the brain. Here, we propose a strategy combining electroacupuncture (EA) stimulation of the Dazhui acupoint (GV14) with polyphenol-mediated conductive hydrogel microneedles to promote diabetic wound healing and alleviate depression through local wound–brain interactions. The conductive microneedles comprised methacrylated gelatin, dopamine (DA), DA-modified poly(3,4-ethylenedioxythiophene), and Lycium barbarum polysaccharide. EA at GV14 activated the vagus–adrenal axis to inhibit systemic inflammation while DA coupled electrical signals for long-term inhibition of local wound inflammation. EA at GV14 was also found to elevate 5-hydroxytryptamine levels in rats with diabetic wounds, consequently mitigating depressive-like behaviors. Additionally, the polyphenol-mediated conductive hydrogel microneedles, and coupled with EA stimulation promoted healing of wound tissue and peripheral nerves. This strategy regulated both local and systemic inflammation while alleviating depressive-like behaviors in diabetic rats, providing a new clinical perspective for the treatment of diabetes-related and emotional disorders.

Innovations in Peripheral Nerve Regeneration.

The field of peripheral nerve regeneration is a dynamic and rapidly evolving area of research that continues to captivate the attention of neuroscientists worldwide. The quest for effective treatments and therapies to enhance the healing of peripheral nerves has gained significant momentum in recent years, as evidenced by the substantial increase in publications dedicated to this field. This surge in interest reflects the growing recognition of the importance of peripheral nerve recovery and the urgent need to develop innovative strategies to address nerve injuries. In this context, this article aims to contribute to the existing knowledge by providing a comprehensive review that encompasses both biomaterial and clinical perspectives. By exploring the utilization of nerve guidance conduits and pharmacotherapy, this article seeks to shed light on the remarkable advancements made in the field of peripheral nerve regeneration. Nerve guidance conduits, which act as artificial channels to guide regenerating nerves, have shown promising results in facilitating nerve regrowth and functional recovery. Additionally, pharmacotherapy approaches have emerged as potential avenues for promoting nerve regeneration, with various therapeutic agents being investigated for their neuroprotective and regenerative properties. The pursuit of advancing the field of peripheral nerve regeneration necessitates persistent investment in research and development. Continued exploration of innovative treatments, coupled with a deeper understanding of the intricate processes involved in nerve regeneration, holds the promise of unlocking the complete potential of these groundbreaking interventions. By fostering collaboration among scientists, clinicians, and industry partners, we can accelerate progress in this field, bringing us closer to the realization of transformative therapies that restore function and quality of life for individuals affected by peripheral nerve injuries.

Type I collagen extracellular matrix facilitates nerve regeneration via the construction of a favourable microenvironment.

The extracellular matrix (ECM) provides essential physical support and biochemical cues for diverse biological activities, including tissue remodelling and regeneration, and thus is commonly applied in the construction of artificial peripheral nerve grafts. Nevertheless, the specific functions of essential peripheral nerve ECM components have not been fully determined. Our research aimed to differentially represent the neural activities of main components of ECM on peripheral nerve regeneration. Schwann cells from sciatic nerves and neurons from dorsal root ganglia were isolated and cultured in vitro. The cells were seeded onto noncoated dishes, Matrigel-coated dishes, and dishes coated with the four major ECM components fibronectin, laminin, collagen I, and collagen IV. The effects of these ECM components on Schwann cell proliferation were determined via methylthiazolyldiphenyl-tetrazolium bromide (MTT), Cell Counting Kit-8, and 5-ethynyl-2'-deoxyuridine (EdU) assays, whereas their effects on cell migration were determined via wound healing and live-cell imaging. Neurite growth in neurons cultured on different ECM components was observed. Furthermore, the two types of collagen were incorporated into chitosan artificial nerves and used to repair sciatic nerve defects in rats. Immunofluorescence analysis and a behavioural assessment, including gait, electrophysiology, and target muscle analysis, were conducted. ECM components, especially collagen I, stimulated the DNA synthesis and movement of Schwann cells. Direct measurement of the neurite lengths of neurons cultured on ECM components further revealed the beneficial effects of ECM components on neurite outgrowth. Injection of collagen I into chitosan and poly(lactic-co-glycolic acid) artificial nerves demonstrated that collagen I facilitated axon regeneration and functional recovery after nerve defect repair by stimulating the migration of Schwann cells and the formation of new blood vessels. In contrast, collagen IV recruited excess fibroblasts and inflammatory macrophages and thus had disadvantageous effects on nerve regeneration. These findings reveal the modulatory effects of specific ECM components on cell populations of peripheral nerves, reveal the contributing roles of collagen I in microenvironment construction and axon regeneration, and highlight the use of collagen I for the healing of injured peripheral nerves.

Bredigite-Based Bioactive Nerve Guidance Conduit for Pro-Healing Macrophage Polarization and Peripheral Nerve Regeneration.

Structural and functional healing of peripheral nerves damaged by trauma or chronic disease remain major clinical challenges, requiring the development of an effective nerve guidance conduit (NGC). The present study investigates a NGC fabrication strategy based on bredigite (BRT, Ca7MgSi4O16) bioceramic for the treatment of peripheral nerve injury. Here, BRT bioceramic shows good biocompatibility and sustainable release of Ca2+, Mg2+, and Si4+ ions. Both BRT extracts and BRT-incorporating electrospun membranes promote the proliferation and myelination potential of RSC96 cells, as well as accelerate vascular formation by human umbilical vein endothelial cells. Notably, BRT facilitates RAW 264.7 cell polarization to the pro-healing phenotype under LPS-induced inflammatory stimulation. More importantly, the macrophages activated by BRT in turn promote RSC96 cell migration and remyelination. In a rat sciatic nerve defect model, improved electrophysiological performance and alleviated gastrocnemius muscle atrophy are observed at 12 weeks post-implantation. Further experiments verify that BRT-loaded NGC facilitates axonal regrowth and revascularization with high M2-like macrophage infiltration. These findings support the beneficial effects of BRT for creating a pro-healing immune microenvironment and orchestrating multicellular processes associated with functional nerve regeneration, indicating the potential of rationally engineered bioceramics as safe, effective, and economical materials for peripheral nerve repair.

Allogenic bone marrow-derived mesenchymal stem cells and its conditioned media for repairing acute and sub-acute peripheral nerve injuries in a rabbit model

The present study evaluated healing potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) and BM-MSCs-conditioned medium (BM-MSCs-CM) for acute and subacute injuries in the rabbit peripheral nerve injury model. The regenerative capacity of MSCs was evaluated in 40 rabbits divided into eight groups, four groups each for acute and subacute injury models. BM-MSCs and BM-MSCS-CM were prepared by isolating allogenic bone marrow from the iliac crest. After inducing sciatic nerve crush injury, different treatments consisting of PBS, Laminin, BM-MSCs + laminin, and BM-MSCS-CM + laminin were used on the day of injury in the acute injury model and after ten days of crush injury in the subacute groups. The parameters studied included: pain, total neurological score, gastrocnemius muscle weight and volume ratio, histopathology of the sciatic nerve and gastrocnemius muscle, and scanning electron microscopy (SEM). Findings indicate that BM-MSCs and BM-MSCS-CM have augmented the regenerative capacity in acute and subacute injury groups with a slightly better improvement in the subacute groups than the animals in acute injury groups. Histopathology data revealed different levels of regenerative process undergoing in the nerve. Neurological observations, gastrocnemius muscle evaluation, muscle histopathology, and the SEM results depicted better healing in animals treated with BM-MSCs and BM-MSCS-CM. With this data, it could be concluded that BM-MSCs support the healing of injured peripheral nerves, and the BM-MSCS-CM does accelerate the healing of acute and subacute peripheral nerve injuries in rabbits. However, stem cell therapy may be indicated during the subacute phase for better results.

Multifunctional biomimetic hydrogel based on graphene nanoparticles and sodium alginate for peripheral nerve injury therapy.

Peripheral nerve injury (PNI) caused by injury may influence the patients' lifelong mobility unless there is an appropriate treatment. Tissue engineering has become a hot field to replace traditional autologous nerve transplantation due to its low surgical damage and easy-to-industrial advantages. Graphene (GR) is a kind of carbon nanomaterial with good electrical and mechanical properties that satisfy the demand for a good tissue scaffold for nerve regeneration. Herein, a novel and biosafe hydrogel is fabricated by using graphene and sodium alginate (GR-SA) together. This hydrogel not only can mimic the nerve growth microenvironment but also can promote the expression of neurotrophic substances and growth factors. Additionally, GR-SA hydrogel can significantly reduce inflammatory factors. Moreover, the results of both in vitro and in vivo tests demonstrate that GR-SA hydrogel has a promising prospect in PNI regeneration.

LONG TERM EFFECTS OF ALLANTOIN ON PERIPHERAL NERVE HEALING: AN ELECTROPHYSIOLOGICAL STUDY

Background: Peripheral nerve injuries are a common health problem resulting in a decreased quality of life. Treatment of peripheral nerve injuries is complex and depends on location, intensity, and type of nerve injury. Allantoin is an antioxidant found in plants that enhance wound healing. It promotes the proliferation of cells by improving peripheral nerve function. This study aimed to investigate the long term effects of intraperitoneal (i.p.) administration of allantoin on peripheral nerve healing in an experimental sciatic nerve crush in a rat model. Materials and Methods: Twenty male Wistar albino rats were randomly divided into four groups. Control (Cont) Group did not receive any special protocol for 60 days. Crush (Cr) Group was induced to crush. Allantoin (A) Group received 10 mg/kg of allantoin i.p. for 60 days. Crush + Allantoin (Cr+A) Group was induced to crush and given 10 mg/kg of allantoin i.p. for 60 days. After 60 days all rats were sacrificed following electromyography (EMG). Results: Allantoin was revealed to enhance the peripheral nerve function in terms of amplitude and latency. Conclusion: The i.p. administration of allantoin may have a positive effect on peripheral nerve healing.

Role of Corticosteroids versus Hyaluronic Acid in Healing of Sciatic Nerve Injury in Male Albino Rats

Background: Peripheral nerve lesions are common and severe injuries that impact about 2.8% of traumatic patients annually, and result in lifetime disability if untreated. Objective: This study aimed to investigate the effect of corticosteroids vs hyaluronic acid in peripheral nerve healing in rats. Patients and methods: This was experimental and histopathological study that had included (18) Sprague-Dawley rats with an average weight of 300–350 gm. All rats were divided into three groups (n=6 per group). Group 1; Corticosteroids was injected under epineurium after primary repair. Group 2; Hyaluronic acid group: the site of anastomosis was coated by hyaluronic acid after primary repair. Group 3; Primary repair only was done. Results: 100% of cases in group 1 and group 2 showed satisfactory wound healing and 83.3% in group3 showed satisfactory wound healing with no significant difference between them. Conclusion: There was an increase in the number of regenerated nerve fibers in the corticosteroids and hyaluronic acid especially on the distal end in comparison to the control group.

Peripheral Nerve Healing: So Near and Yet So Far.

Peripheral nerve injuries represent a considerable portion of chronic disability that especially affects the younger population. Prerequisites of proper peripheral nerve injury treatment include in-depth knowledge of the anatomy, pathophysiology, and options in surgical reconstruction. Our greater appreciation of nerve healing mechanisms and the development of different microsurgical techniques have significantly refined the outcomes in treatment for the past four decades. This work reviews the peripheral nerve regeneration process after an injury, provides an overview of various coaptation methods, and compares other available treatments such as autologous nerve graft, acellular nerve allograft, and synthetic nerve conduits. Furthermore, the formation of neuromas as well as their latest treatment options are discussed.

Hedging against Neuropathic Pain: Role of Hedgehog Signaling in Pathological Nerve Healing.

The peripheral nervous system has important regenerative capacities that regulate and restore peripheral nerve homeostasis. Following peripheral nerve injury, the nerve undergoes a highly regulated degeneration and regeneration process called Wallerian degeneration, where numerous cell populations interact to allow proper nerve healing. Recent studies have evidenced the prominent role of morphogenetic Hedgehog signaling pathway and its main effectors, Sonic Hedgehog (SHH) and Desert Hedgehog (DHH) in the regenerative drive following nerve injury. Furthermore, dysfunctional regeneration and/or dysfunctional Hedgehog signaling participate in the development of chronic neuropathic pain that sometimes accompanies nerve healing in the clinical context. Understanding the implications of this key signaling pathway could provide exciting new perspectives for future research on peripheral nerve healing.

The effect of lithium and lithium-loaded hyaluronic acid hydrogel applications on nerve regeneration and recovery of motor functions in peripheral nerve injury

Functional recovery rates after peripheral nerve injury are quite poor. Studies have focused on the organization of axonal development and the alteration of the microenvironment of the regenerated nerve. It is a frequently used repair method to place a tube to the incision area with tubulization technique and to try increasing the effect by filling the tube with various substances. Hyaluronic acid is a natural polysaccharide, and since it is biodegradable, it makes an ideal biomaterial in peripheral nerve healing. Lithium chloride (LiCl), a Glycogen synthase kinase 3β (GSK3β) inhibitor, is also frequently used in the treatment of bipolar and depressive disorders, but it has strong neuroprotective and antiinflammatory effects. In this study, peripheral nerve injury was induced on the rat sciatic nerve and silicon conduit was placed to this area and the effects of application of LiCl (2.5, 5 and 15 mEq doses) and LiCl (15 mEq)-loaded hyaluronic acid hydrogel in the conduit on peripheral nerve regeneration and improvement of motor functions were investigated. Sciatic nerve index (SFI) was measured at 2nd, 4th, 8th, and 12th weeks for each animal. Histological, microscopic, and morphometrical analyzes were evaluated at the end of the experiment (12th weeks). Our results indicate that topically applied lithium has positive effect after peripheral nerve injury and especially 5 mEq LiCl can increase nerve regeneration in rats. Further studies are needed to discuss the morphological, molecular and mechanical potential of treatment application.

Non-thermal plasma accelerates the healing process of peripheral nerve crush injury in rats.

The objective of this study was to evaluate the effect of non-thermal plasma (NTP) on the healing process of peripheral nerve crush injuries, which can occur during dental implant procedures. For this, a rat model of sciatic nerve crush injury (SNCI) was adopted. The rats were divided into three groups: non-nerve damage (non-ND), nerve damage (ND), and ND+NTP group. To evaluate the sciatic nerve (SN) function, the static sciatic index was calculated, and the muscle and SN tissues were subjected to a histologic analysis. The results showed that NTP effectively accelerated the healing process of SNCI in rats. In contrast to the ND group, which showed approximately 60% recovery in the SN function, the NTP-treated rats showed complete recovery. Histologically, the NTP treatments not only accelerated the muscle healing, but also reduced the edema-like phenotype of the damaged SN tissues. In the ND group, the SN tissues had an accumulation of CD68-positive macrophages, partially destroyed axonal fibers and myelinated Schwann cells. Conversely, in the ND+NTP group, the macrophage accumulation was reduced and an overall regeneration of the damaged axon fibers and the myelin sheath was accomplished. The results of this study indicate that NTP can be used for healing of injured peripheral nerves.

Alpha-Tocopherol and Cyanocobalamin Combination Accelerates Peripheral Nerve Healing: An Experimental Animal Study.

To evaluate the functional and histopathological results of alpha-tocopherol (vitamin E) and vitamin B12 on an experimental rat model of peripheral nerve injury. This research included 32 Wistar Hannover rats. The sciatic nerves of the animals were crushed using an aneurysm clamp. The rats were divided into 4 groups, as group 0 (the controls; no treatment), and groups B12, E, and B12+E, respectively. The rats were analyzed functionally, using the sciatic functional index (SFI), and histopathologically. In the functional analysis, it was determined that vitamin E was as influential as B12. Concomitant use of these 2 vitamins was found to be more beneficial. The SFI was significantly higher in the B12+E group when compared with that of the B12 group, which indicated that vitamin E improved the healing effects of vitamin B12. In the histopathological evaluation, vitamin E was not effective in the treatment of axonal degeneration (AxD) or edema/inflammation (EI) by itself. Although vitamin B12 was effective in the treatment of EI, it was ineffective in the treatment of AxD. However, the combination of these vitamins decreased both AxD and EI, which showed that the additive effects of these vitamins could reverse neurological injury when used together. Vitamins B12 and E were effective in the functional recovery of peripheral nerve injury (PNI). Neither vitamin B12 nor E was effective in the treatment AxD; however, their combination was effective in the treatment of AxD. The results suggested that vitamin E was effective in the treatment of PNI, especially when combined with vitamin B12. It is our belief that the combination of these vitamins could be used in the treatment of PNI, especially after future studies have been conducted on humans.

Effect of Tarantula Cubensis Extract (Theranekron) on Peripheral Nerve Healing in an Experimental Sciatic Nerve Injury Model in Rats.

To investigate the effects of systemic application of Theranekron on peripheral nerve healing after compression type peripheral nerve injury. Twenty-one female Wistar albino rats were randomly divided into 3 groups (n=7): Control (C), injury (I), and Theranekron (T). The right sciatic nerves of rats in the I and T groups were compressed via an aneurysm clip for 5 minutes and 0.3 ml Theranekron D6 was applied via subcutaneous administration once a week in the T group for a total period of four weeks. Nerve conduction velocity and proximal and distal latency of the rats were measured at the end of day 30. The right sciatic nerves of the rats were then removed and myelin damage grading, axon counting, fibrosis assessment, caspase-3, and NF-kB immunochemical staining were performed. The data were analysed statistically and a p value of less than 0.05 was considered to be significant. Axonal degeneration, vacuolization and myelin destruction were found to be markedly greater in group T. Fibrosis and caspase-3 immunoreactivity were less intense in group T. There was a statistically significant difference in the electrophysiological results of groups I and T. However, there were no statistically significant differences in axon number and NF-kB immunochemical evaluation of groups I and T. The findings of this study show that Theranekron decreases axonal and myelin damage after sciatic nerve injury and that this neuroprotective effect of Theranekron can be attributed to its anti-inflammatory effect on pro-inflammatory cytokine levels.

Implications of Aging in Plastic Surgery.

Given the rapidly aging population, investigating the effect of age on plastic surgery outcomes is imperative. Despite this, the topic has received relatively little attention. Furthermore, there appears to be little integration between the basic scientists investigating the mechanisms of aging and the plastic surgeons providing the majority of "antiaging" therapies. This review first provides a description of the effects and mechanisms of aging in 5 types of tissue: skin, adipose tissue, muscles, bones and tendons, and nervous tissue followed by an overview of the basic mechanisms underlying aging, presenting the currently proposed cellular and molecular theories. Finally, the impact of aging, as well as frailty, on plastic surgery outcomes is explored by focusing on 5 different topics: general wound healing and repair of cutaneous tissue, reconstruction of soft tissue, healing of bones and tendons, healing of peripheral nerves, and microsurgical reconstruction. We find mixed reports on the effect of aging or frailty on outcomes in plastic surgery, which we hypothesize to be due to exclusion of aged and frail patients from surgery as well as due to outcomes that reported no postsurgical issues with aged patients. As plastic surgeons continue to interact more with the growing elderly population, a better appreciation of the underlying mechanisms and outcomes related to aging and a clear distinction between chronological age and frailty can promote better selection of patients, offering appropriate patients surgery to improve an aged appearance, and declining interventions in inappropriate patients.

The Effect of Vascular Graft and Human Umbilical Cord Blood-Derived CD34+ Stem Cell on Peripheral Nerve Healing.

AIM:There are many trials concerning peripheral nerve damage causes and treatment options. Unfortunately, nerve damage is still a major problem regarding health, social and economic issues. On this study, we used vascular graft and human cord blood derived stem cells to find an alternative treatment solution to this problem.MATERIAL AND METHODS:We used 21 female Wistar rats on our study. They were anesthetized with ketamine and we studied right hind limbs. On Group 1, we did a full layer cut on the right sciatic nerve. On Group 2, we did a full layer cut on the right sciatic nerve, and we covered synthetic vascular graft on cut area. On Group 3, we did a full layer cut on right sciatic nerve, and we covered the area with stem cell applied vascular graft.RESULTS:At the end of postoperative 8. weeks, we performed EMG on the rats. When we compared healthy and degenerated areas as a result of EMG, we found significant amplitude differences between the groups on healthy areas whereas there was no significant difference on degenerated areas between the groups. Then we re-opened the operated area again to reveal the sciatic nerve cut area, and we performed electron microscope evaluation. On the stem cell group, we observed that both the axon and the myelin sheet prevented degeneration.CONCLUSION:This study is a first on using synthetic vascular graft and cord blood derived CD34+ cells in peripheral nerve degeneration. On the tissues that were examined with electron microscope, we observed that CD34+ cells prevented both axonal and myelin sheath degeneration. Nerve tissue showed similar results to the control group, and the damage was minimal.

Emerging Strategies on Adjuvant Therapies for Nerve Recovery

Current strategies for promoting faster and more effective peripheral nerve healing have utilized a wide variety of techniques and approaches. Nerve grafts, conduits, and stem cell therapy all have their respective advantages. However, there are still some difficulties in attaining complete functional recovery with a single treatment modality. The utilization of adjuvant treatments, in combination with current standard-of-care methods, offers the potential to improve patient outcomes. This paper highlights the current landscape of adjuvanttreatments for enhancing peripheral nerve repair and regeneration.

The effect of tacrolimus on facial nerve injury: Histopathological findings in a rabbit model

HypothesisTacrolimus helps healing of facial nerve injury. BackgroundPositive effects of tacrolimus on axon regeneration and healing of injured peripheral nerves (eg. sciatic nerve) have been reported in the literature. Tacrolimus may be an additional treatment method that could improve the nerve healing after surgical treatment of cut injury of facial nerve. Methods20 New Zealand rabbits were randomly separated into control and study groups of 10. In control group, no medical treatment was given after facial nerve anastomosis, and the animals were followed up for 2months. In the study group rabbits were given 1mg/kg/day tacrolimus subcutaneously for 2months after the facial nerve anastomosis. The histopathologic findings of axon regeneration like axon myelination were analyzed in both groups under electron and light microscopy. The data obtained in the groups were compared. ResultsGreater axon diameters, thicker myelin sheaths, and higher total number of myelinated axons were found in the tacrolimus group, suggesting better regeneration in this group when compared to the control group. There was less vacuolar degeneration in the study group. All these findings suggest that tacrolimus positively affects healing after facial nerve anastomosis. ConclusionThe results of this study indicate that tacrolimus has favorable effects on the healing process of the facial nerve after end-to-end anastomosis. Tacrolimus may be a promising agent in the future for nerve regeneration following traumatic facial paralysis surgery.

Calculated spinal cord electric fields and current densities for possible neurite regrowth from quasi-DC electrical stimulation.

The prime goal of this work was to model essentially steady (DC) fields from electrodes, implanted in several ways, which have been suggested as possible means to encourage nerve fiber regrowth in spinal cord injuries. A simplified model of the human spinal cord in the lumbar region and the SEMCAD-X computer program were used to calculate electric field and current density patterns from electrodes outside vertebrae and those inserted extradurally within the spinal canal. DC electric fields guide nerve growth in developing organisms and in vitro. They also have been shown to encourage healing of injured peripheral nerves, and application of a longitudinal field has been used in attempts to bridge spinal cord injuries. When calculated results are scaled to the experimental level used in the literature, all modeled electrodes produced fields in the spinal cord below fields needed in the literature for stimulation of spinal as well as peripheral nerve growth in vitro, in dogs, and in a published clinical human trial. The highly-conducting cerebrospinal fluid appeared to provide effective shielding; there was also a very high degree of polarization at electrodes.