scholarly journals Functional Recovery via Preregenerated Nerve Graft in Rat Sciatic Nerve Injury Model

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Umang Khandpur ◽  
Ying Yan ◽  
Wilson Zachary Ray ◽  
Matthew R MacEwan
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Functional Recovery ◽  
Peripheral Nerve Injury ◽  
Muscle Force ◽  
Nerve Graft ◽  
Tissue Loss ◽  
Limb Amputation ◽  
Percent Recovery

Abstract INTRODUCTION Patients who have experienced major tissue loss with peripheral nerve injury (eg, limb amputation) may be offered composite tissue allotransplantation (CTA). The return of sensory ability and cosmetic component of CTAs make them an attractive alternative to prosthetic devices. Unfortunately, robust reinnervation especially over great distances remains an issue for hand allotransplants. In this study, we introduce a preregenerated nerve graft to shorten the distance and therefore time to terminal tissue reinnervation, which could improve the utility of CTAs. METHODS A total of 18 rats weighing 250 to 300 gm each were randomized into 1 of 3 groups: baseline, fresh, or preregenerated. The baseline group underwent sham surgery to obtain baseline functional data. The fresh and preregenerated groups both underwent grafting of the sciatic nerve but the preregenerated group utilized 8-wk preregenerated grafts. At postperative week 8 from distal neurorrhaphy, both groups underwent terminal functional testing via EMG and evoked muscle force. RESULTS The preregenerated group had significantly greater mean EMG (P < .05) and maximum tetanic muscle force values (P < .05) than the fresh group. Mean percent recovery in EMG for the fresh group was 21.95% compared with 81.79% in the preregenerated group. Mean percent recovery in muscle force was 9.46% and 33.15%, respectively. CONCLUSION The results of this study provide a novel approach to enhance final functional recovery after peripheral nerve injury. The current practice of constructing a nerve stump may be improved by grafting a nerve segment at the time of injury and allowing it to preregenerate into local musculature so that if a CTA is later performed, an expedited and more robust reinnervation could be accomplished.

scholarly journals Reviving Matrix for Nerve Reconstruction in Rabbit Model of Chronic Peripheral Nerve Injury With Massive Loss Defect

2021 ◽  
Vol 7 ◽  
Author(s):  
Shimon Rochkind ◽  
Mara Almog ◽  
Sigal Meilin ◽  
Zvi Nevo
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Rabbit Model ◽  
Nerve Graft ◽  
Human Condition ◽  
Nerve Reconstruction ◽  
Chronic Injury ◽  
Empty Tube

Background and Aims: The aim of this study was to investigate the innovative guiding regenerative gel (GRG) and antigliotic GRG (AGRG) fillings for nerve conduits, prepared with Food and Drug Administration (FDA)-approved agents and expected to provide an alternative to autologous nerve graft and to enable reconnection of massive nerve gaps in a rabbit model of chronic peripheral nerve injury with massive loss defect that simulates the human condition of chronic injury with a large gap.Methods: The components and dosimetry for GRG and AGRG formulations were investigated in vitro on nerve cell culture and in vivo on 10-mm reconstructed sciatic nerves of 72 rats using different concentrations of agents and completed on a rabbit model of delayed (chronic) complete peripheral nerve injury with a 25-mm gap. Forty rabbits underwent delayed (9 weeks after complete injury of the tibial portion of the sciatic nerve) nerve tube reconstruction of a gap that is 25 mm long. GRG and AGRG groups were compared with autologous and empty tube reconstructed groups. Rats and rabbits underwent electrophysiological and histochemical assessments (19 weeks for rats and 40 weeks for rabbits).Results: Application of AGRG showed a significant increase of about 78% in neurite length per cell and was shown to have the most promising effect on neuronal outgrowth, with total number of neurites increasing by 4-fold. The electrophysiological follow-up showed that AGRG treatment is most promising for the reconstruction of the tibial portion of the sciatic nerve with a critical gap of 25 mm. The beneficial effect of AGRG was found when compared with the autologous nerve graft reconstruction. Thirty-one weeks post the second surgery (delayed reconstruction), histochemical observation showed significant regeneration after using AGRG neurogel, compared with the empty tube, and succeeded in significantly regenerating the nerve, as well as the autologous nerve graft, which was almost similar to a healthy nerve.Conclusion: We demonstrate that in the model of delayed peripheral nerve repair with massive loss defect, the application of AGRG led to a stronger nerve recovery and can be an alternative to autologous nerve graft.

scholarly journals The long noncoding RNA Arrl1 inhibits neurite outgrowth by functioning as a competing endogenous RNA during neuronal regeneration in rats

2020 ◽  
Vol 295 (25) ◽  
pp. 8374-8386 ◽  
Author(s):  
Dong Wang ◽  
Yanping Chen ◽  
Mingwen Liu ◽  
Qianqian Cao ◽  
Qihui Wang ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Neurite Outgrowth ◽  
Nerve Injury ◽  
Functional Recovery ◽  
Peripheral Nerve Injury ◽  
Axon Regeneration ◽  
Neuronal Regeneration ◽  
Competing Endogenous Rna ◽  
Drg Neurons

The intrinsic regeneration ability of neurons is a pivotal factor in the repair of peripheral nerve injury. Therefore, identifying the key modulators of nerve regeneration may help improve axon regeneration and functional recovery after injury. Unlike for classical transcription factors and regeneration-associated genes, the function of long noncoding RNAs (lncRNAs) in the regulation of neuronal regeneration remains mostly unknown. In this study, we used RNA-Seq–based transcriptome profiling to analyze the expression patterns of lncRNAs and mRNAs in rat dorsal root ganglion (DRG) following sciatic nerve injury. Analyses using the lncRNA-mRNA co-expression network, gene ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes pathway databases indicated that the lncRNA Arrl1 decreases neurite outgrowth after neuronal injury. shRNA-mediated Arrl1 silencing increased axon regeneration both in vitro and in vivo and improved functional recovery of the sciatic nerve. Moreover, inhibiting an identified target gene of Arrl1, cyclin-dependent kinase inhibitor 2B (Cdkn2b), markedly promoted neurite outgrowth of DRG neurons. We also found that Arrl1 acts as a competing endogenous RNA that sponges a Cdkn2b repressor, microRNA-761 (miR-761), and thereby up-regulates Cdkn2b expression during neuron regeneration. We conclude that the lncRNA Arrl1 affects the intrinsic regeneration of DRG neurons by derepressing Cdkn2b expression. Our findings indicate a role for an lncRNA-microRNA-kinase pathway in the regulation of axon regeneration and functional recovery following peripheral nerve injury in rats.

scholarly journals Upslope treadmill exercise enhances motor axon regeneration but not functional recovery following peripheral nerve injury

2016 ◽  
Vol 116 (3) ◽  
pp. 1408-1417 ◽  
Author(s):  
Jill Cannoy ◽  
Sam Crowley ◽  
Allen Jarratt ◽  
Kelly LeFevere Werts ◽  
Krista Osborne ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Functional Recovery ◽  
Peripheral Nerve Injury ◽  
Axon Regeneration ◽  
Motor Axon ◽  
Emg Activity ◽  
Daily Exercise ◽  
Muscle Reinnervation

Following peripheral nerve injury, moderate daily exercise conducted on a level treadmill results in enhanced axon regeneration and modest improvements in functional recovery. If the exercise is conducted on an upwardly inclined treadmill, even more motor axons regenerate successfully and reinnervate muscle targets. Whether this increased motor axon regeneration also results in greater improvement in functional recovery from sciatic nerve injury was studied. Axon regeneration and muscle reinnervation were studied in Lewis rats over an 11 wk postinjury period using stimulus evoked electromyographic (EMG) responses in the soleus muscle of awake animals. Motor axon regeneration and muscle reinnervation were enhanced in slope-trained rats. Direct muscle (M) responses reappeared faster in slope-trained animals than in other groups and ultimately were larger than untreated animals. The amplitude of monosynaptic H reflexes recorded from slope-trained rats remained significantly smaller than all other groups of animals for the duration of the study. The restoration of the amplitude and pattern of locomotor EMG activity in soleus and tibialis anterior and of hindblimb kinematics was studied during treadmill walking on different slopes. Slope-trained rats did not recover the ability to modulate the intensity of locomotor EMG activity with slope. Patterned EMG activity in flexor and extensor muscles was not noted in slope-trained rats. Neither hindblimb length nor limb orientation during level, upslope, or downslope walking was restored in slope-trained rats. Slope training enhanced motor axon regeneration but did not improve functional recovery following sciatic nerve transection and repair.

Changes in Crossed Spinal Reflexes After Peripheral Nerve Injury and Repair

2002 ◽  
Vol 87 (4) ◽  
pp. 1763-1771 ◽  
Author(s):  
Antoni Valero-Cabré ◽  
Xavier Navarro
Keyword(s):  
Sciatic Nerve ◽  
Action Potential ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Tibialis Anterior ◽  
Tibial Nerve ◽  
Spinal Reflexes ◽  
Injury And Repair

We investigated the changes induced in crossed extensor reflex responses after peripheral nerve injury and repair in the rat. Adults rats were submitted to non repaired sciatic nerve crush (CRH, n = 9), section repaired by either aligned epineurial suture (CS, n = 11) or silicone tube (SIL4, n = 13), and 8 mm resection repaired by tubulization (SIL8, n = 12). To assess reinnervation, the sciatic nerve was stimulated proximal to the injury site, and the evoked compound muscle action potential (M and H waves) from tibialis anterior and plantar muscles and nerve action potential (CNAP) from the tibial nerve and the 4th digital nerve were recorded at monthly intervals for 3 mo postoperation. Nociceptive reinnervation to the hindpaw was also assessed by plantar algesimetry. Crossed extensor reflexes were evoked by stimulation of the tibial nerve at the ankle and recorded from the contralateral tibialis anterior muscle. Reinnervation of the hindpaw increased progressively with time during the 3 mo after lesion. The degree of muscle and sensory target reinnervation was dependent on the severity of the injury and the nerve gap created. The crossed extensor reflex consisted of three bursts of activity (C1, C2, and C3) of gradually longer latency, lower amplitude, and higher threshold in control rats. During follow-up after sciatic nerve injury, all animals in the operated groups showed recovery of components C1 and C2 and of the reflex H wave, whereas component C3 was detected in a significantly lower proportion of animals in groups with tube repair. The maximal amplitude of components C1 and C2 recovered to values higher than preoperative values, reaching final levels between 150 and 245% at the end of the follow-up in groups CRH, CS, and SIL4. When reflex amplitude was normalized by the CNAP amplitude of the regenerated tibial nerve, components C1 (300–400%) and C2 (150–350%) showed highly increased responses, while C3 was similar to baseline levels. In conclusion, reflexes mediated by myelinated sensory afferents showed, after nerve injuries, a higher degree of facilitation than those mediated by unmyelinated fibers. These changes tended to decline toward baseline values with progressive reinnervation but still remained significant 3 mo after injury.

scholarly journals SUR1, newly expressed in astrocytes, mediates neuropathic pain in a mouse model of peripheral nerve injury

2021 ◽  
Vol 17 ◽  
pp. 174480692110066
Author(s):  
Orest Tsymbalyuk ◽  
Volodymyr Gerzanich ◽  
Aaida Mumtaz ◽  
Sanketh Andhavarapu ◽  
Svetlana Ivanova ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Dorsal Horn ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Thermal Sensitivity ◽  
Gradual Improvement ◽  
Pain Behaviors

Background Neuropathic pain following peripheral nerve injury (PNI) is linked to neuroinflammation in the spinal cord marked by astrocyte activation and upregulation of interleukin 6 (IL -6 ), chemokine (C-C motif) ligand 2 (CCL2) and chemokine (C-X-C motif) ligand 1 (CXCL1), with inhibition of each individually being beneficial in pain models. Methods Wild type (WT) mice and mice with global or pGfap-cre- or pGFAP-cre/ERT2-driven Abcc8/SUR1 deletion or global Trpm4 deletion underwent unilateral sciatic nerve cuffing. WT mice received prophylactic (starting on post-operative day [pod]-0) or therapeutic (starting on pod-21) administration of the SUR1 antagonist, glibenclamide (10 µg IP) daily. We measured mechanical and thermal sensitivity using von Frey filaments and an automated Hargreaves method. Spinal cord tissues were evaluated for SUR1-TRPM4, IL-6, CCL2 and CXCL1. Results Sciatic nerve cuffing in WT mice resulted in pain behaviors (mechanical allodynia, thermal hyperalgesia) and newly upregulated SUR1-TRPM4 in dorsal horn astrocytes. Global and pGfap-cre-driven Abcc8 deletion and global Trpm4 deletion prevented development of pain behaviors. In mice with Abcc8 deletion regulated by pGFAP-cre/ERT2, after pain behaviors were established, delayed silencing of Abcc8 by tamoxifen resulted in gradual improvement over the next 14 days. After PNI, leakage of the blood-spinal barrier allowed entry of glibenclamide into the affected dorsal horn. Daily repeated administration of glibenclamide, both prophylactically and after allodynia was established, prevented or reduced allodynia. The salutary effects of glibenclamide on pain behaviors correlated with reduced expression of IL-6, CCL2 and CXCL1 by dorsal horn astrocytes. Conclusion SUR1-TRPM4 may represent a novel non-addicting target for neuropathic pain.

Transplantation of Schwann cells in a collagen tube for the repair of large, segmental peripheral nerve defects in rats

2013 ◽  
Vol 119 (3) ◽  
pp. 720-732 ◽  
Author(s):  
Yerko A. Berrocal ◽  
Vania W. Almeida ◽  
Ranjan Gupta ◽  
Allan D. Levi
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Fluorescent Protein ◽  
Control Groups ◽  
Myelinated Axons ◽  
Segmental Nerve ◽  
Green Fluorescent

Object Segmental nerve defects pose a daunting clinical challenge, as peripheral nerve injury studies have established that there is a critical nerve gap length for which the distance cannot be successfully bridged with current techniques. Construction of a neural prosthesis filled with Schwann cells (SCs) could provide an alternative treatment to successfully repair these long segmental gaps in the peripheral nervous system. The object of this study was to evaluate the ability of autologous SCs to increase the length at which segmental nerve defects can be bridged using a collagen tube. Methods The authors studied the use of absorbable collagen conduits in combination with autologous SCs (200,000 cells/μl) to promote axonal growth across a critical size defect (13 mm) in the sciatic nerve of male Fischer rats. Control groups were treated with serum only–filled conduits of reversed sciatic nerve autografts. Animals were assessed for survival of the transplanted SCs as well as the quantity of myelinated axons in the proximal, middle, and distal portions of the channel. Results Schwann cell survival was confirmed at 4 and 16 weeks postsurgery by the presence of prelabeled green fluorescent protein–positive SCs within the regenerated cable. The addition of SCs to the nerve guide significantly enhanced the regeneration of myelinated axons from the nerve stump into the proximal (p < 0.001) and middle points (p < 0.01) of the tube at 4 weeks. The regeneration of myelinated axons at 16 weeks was significantly enhanced throughout the entire length of the nerve guide (p < 0.001) as compared with their number in a serum–only filled tube and was similar in number compared with the reversed autograft. Autotomy scores were significantly lower in the animals whose sciatic nerve was repaired with a collagen conduit either without (p < 0.01) or with SCs (p < 0.001) when compared with a reversed autograft. Conclusions The technique of adding SCs to a guidance channel significantly enhanced the gap distance that can be repaired after peripheral nerve injury with long segmental defects and holds promise in humans. Most importantly, this study represents some of the first essential steps in bringing autologous SC-based therapies to the domain of peripheral nerve injuries with long segmental defects.

scholarly journals Erythropoietin Accelerates Functional Recovery After Peripheral Nerve Injury

2008 ◽  
Vol 90 (8) ◽  
pp. 1644-1653 ◽  
Author(s):  
John C Elfar ◽  
Justin A Jacobson ◽  
J Edward Puzas ◽  
Randy N Rosier ◽  
Michael J Zuscik
Keyword(s):  
Peripheral Nerve ◽  
Nerve Injury ◽  
Functional Recovery ◽  
Peripheral Nerve Injury

Regeneration and functional recovery following peripheral nerve injury

2004 ◽  
Vol 1 (2) ◽  
pp. 177-185 ◽  
Author(s):  
Francisco J. Rodríguez ◽  
Antoni Valero-Cabré ◽  
Xavier Navarro
Keyword(s):  
Peripheral Nerve ◽  
Nerve Injury ◽  
Functional Recovery ◽  
Peripheral Nerve Injury

scholarly journals Expression of Nrf2 Promotes Schwann Cell-Mediated Sciatic Nerve Recovery in Diabetic Peripheral Neuropathy

2018 ◽  
Vol 46 (5) ◽  
pp. 1879-1894 ◽  
Author(s):  
Wei Tang ◽  
Xiangfang Chen ◽  
Haoqi Liu ◽  
Qian Lv ◽  
Junjie Zou ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Rat Model ◽  
Peripheral Nerve Injury ◽  
Signal Pathway ◽  
Inflammatory Factors ◽  
Survival Ratio ◽  
Nrf2 Expression

Background/Aims: High glucose-induced oxidative stress and inflammatory responses play an important role in painful diabetic neuropathy by activating the TLR4/NFκB signal pathway. Schwann cells (SCs) are integral to peripheral nerve biology, contributing to saltatory conduction along axons, nerve and axon development, and axonal regeneration. SCs provide a microenvironment favoring vascular regeneration but their low survival ratio in hyperglycemic conditions suppress the function to promote nerve growth. Nuclear factor erythroid 2-related factor 2 (Nrf2) promotes remyelination after peripheral nerve injury. The aim of this study was to identify the role of Nrf2 in SC-mediated functional recovery after sciatic nerve injury. Methods: We compared plasma inflammatory factors in diabetic patients (DN) with/without diabetic peripheral neuropathy (DPN) and assessed whether Nrf2 expression in SCs could repair peripheral nerve injury in a rat model. Nrf2, TLR4/NFκB signal pathway and apoptosis relative protein expression were detected by western blot. Apoptosis and angiogenesis were determined by immunofluorescence and tubule formation assay, respectively. Regenerated nerves were determined by transmission electron microscope. Results: Higher levels of inflammatory factors and VEGF expression were found in DPN patients. Cellular experiments indicate that Nrf2 expression inhibits hyperglycemia-induced apoptosis and promotes angiogenesis by regulating the TLR4/NFκB signal pathway. Animal experiments show that nerve conduction velocity, myelin sheath thickness, and sciatic vasa nervorum are restored with transplantation of SCs overexpressing Nrf2. Conclusions: Taken together, the high survival ratio of SCs in a DPN rat model indicates that overexpression of Nrf2 restores nerve injury.

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