scholarly journals Effects of treadmill training on functional recovery following peripheral nerve injury in rats

2013 ◽  
Vol 109 (11) ◽  
pp. 2645-2657 ◽  
Author(s):  
Tiffany Boeltz ◽  
Meredith Ireland ◽  
Kristin Mathis ◽  
Jennifer Nicolini ◽  
Karen Poplavski ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Nerve Injury ◽  
Functional Recovery ◽  
Tibialis Anterior ◽  
Axon Regeneration ◽  
Treadmill Training ◽  
Female Rats ◽  
Nerve Transection ◽  
Sciatic Nerve Transection ◽  
Daily Exercise

Exercise, in the form of moderate daily treadmill training following nerve transection and repair leads to enhanced axon regeneration, but its effect on functional recovery is less well known. Female rats were exercised by walking continuously, at a slow speed (10 m/min), for 1 h/day on a level treadmill, beginning 3 days after unilateral transection and surgical repair of the sciatic nerve, and conducted 5 days/wk for 2 wk. In Trained rats, both direct muscle responses to tibial nerve stimulation and H reflexes in soleus reappeared earlier and increased in amplitude more rapidly over time than in Untrained rats. The efficacy of the restored H reflex was greater in Trained rats than in Untrained controls. The reinnervated tibialis anterior and soleus were coactivated during treadmill locomotion in Untrained rats. In Trained animals, the pattern of activation of soleus, but not tibialis anterior, was not significantly different from that found in Intact rats. The overall length of the hindlimb during level and up- and downslope locomotion was conserved after nerve injury in both groups. This conservation was achieved by changes in limb orientation. Limb length was conserved effectively in all rats during downslope walking but only in Trained rats during level and upslope walking. Moderate daily exercise applied immediately after sciatic nerve transection is sufficient to promote axon regeneration, to restore muscle reflexes, and to improve the ability of rats to cope with different biomechanical demands of slope walking.

scholarly journals Tissue Engineered Axon Tracts Serve as Living Scaffolds to Accelerate Axonal Regeneration and Functional Recovery Following Peripheral Nerve Injury in Rats

2019 ◽  
Author(s):  
Kritika S. Katiyar ◽  
Laura A. Struzyna ◽  
Joseph P. Morand ◽  
Justin C. Burrell ◽  
Basak Clements ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Functional Recovery ◽  
Peripheral Nerves ◽  
Axonal Regeneration ◽  
Axon Regeneration ◽  
Nerve Transection ◽  
Sciatic Nerve Transection ◽  
Nerve Grafts ◽  
Axonal Regrowth ◽  
Peripheral Axon

AbstractAlthough regeneration of damaged axons in peripheral nerves has long been observed, the mechanisms facilitating this growth are not well characterized. Recently, we demonstrated that host axon regeneration could be greatly enhanced by transplanting engineered living axon tracts to guide outgrowth. Here, we used a model of rat sciatic nerve transection to explore potential mechanisms of this facilitated regeneration and its efficacy in comparison with nerve guidance tubes (NGTs) and autografts. Tissue engineered nerve grafts (TENGs) were developed via “stretch-growth” in mechanobioreactors and consisted of centimeter-scale aligned axonal tracts. Either TENGs, NGTs or autografts (reversed nerve) were then transplanted to bridge a 1 cm segmental gap in the sciatic nerve with the mechanisms of axonal regrowth assessed at 2 weeks and the extent of functional recovery assessed at 16 weeks. We observed numerous host axons growing directly along and intertwining with pre-formed axonal tracts in TENGs. This behavior appears to mimic the action of “pioneer” axons in developmental pathfinding by providing living cues for directed and accelerated outgrowth. Indeed, we found that the rates of axon regeneration were 3-4 fold faster than NGTs and equivalent to autografts. It was also observed that infiltration of host Schwann cells – traditional drivers of peripheral axon regeneration – was both accelerated and progressed directly along TENG axonal tracts. These TENG repairs resulted in levels of functional recovery equivalent to autografts, with each being several fold superior to NGT repairs. This new mechanism – which we term “axon-facilitated axon-regeneration” – may be further exploited to enhance axonal regeneration and functional recovery following neurotrauma.

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.

The long-term functional recovery of repair of sciatic nerve transection with biogenic conduits

Microsurgery ◽  
2012 ◽  
Vol 32 (5) ◽  
pp. 377-382 ◽  
Author(s):  
Vincenzo Penna ◽  
Konstantin Wewetzer ◽  
Beatrix Munder ◽  
G. Bjoern Stark ◽  
Eva M. Lang
Keyword(s):  
Sciatic Nerve ◽  
Functional Recovery ◽  
Nerve Transection ◽  
Sciatic Nerve Transection

scholarly journals Administration of CoCl2 Improves Functional Recovery in a Rat Model of Sciatic Nerve Transection Injury

2018 ◽  
Vol 15 (13) ◽  
pp. 1423-1432 ◽  
Author(s):  
Shuai An ◽  
Meng Zhou ◽  
Zheng Li ◽  
Mingli Feng ◽  
Guanglei Cao ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Functional Recovery ◽  
Rat Model ◽  
Nerve Transection ◽  
Sciatic Nerve Transection

Extracts obtained from predegenerated nerves improve functional recovery after sciatic nerve transection

Microsurgery ◽  
2005 ◽  
Vol 25 (6) ◽  
pp. 486-494 ◽  
Author(s):  
Wieslaw Marcol ◽  
Katarzyna Kotulska ◽  
Magdalena Larysz-Brysz ◽  
Iwona Matuszek ◽  
Edyta Olakowska ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Functional Recovery ◽  
Nerve Transection ◽  
Sciatic Nerve Transection

scholarly journals Chondroitinase ABC reduces time to muscle reinnervation and improves functional recovery after sciatic nerve transection in rats

2012 ◽  
Vol 107 (3) ◽  
pp. 747-757 ◽  
Author(s):  
Manning J. Sabatier ◽  
Bao Ngoc To ◽  
Samuel Rose ◽  
Jennifer Nicolini ◽  
Arthur W. English
Keyword(s):  
Sciatic Nerve ◽  
Functional Recovery ◽  
Time Course ◽  
Emg Activity ◽  
Nerve Transection ◽  
Chondroitinase Abc ◽  
Foot Kinematics ◽  
Sciatic Nerve Transection ◽  
Wide Range ◽  
Treadmill Locomotion

Application of chondroitinase ABC (ChABC) to injured peripheral nerves improves axon regeneration, but it is not known whether functional recovery is also improved. Recordings of EMG activity [soleus (Sol) M response and H reflexes] evoked by nerve stimulation and of Sol and tibialis anterior (TA) EMG activity and hindlimb and foot kinematics during slope walking were made to determine whether ChABC treatment of the sciatic nerve at the time of transection improves functional recovery. Recovery of evoked EMG responses began as multiple small responses with a wide range of latencies that eventually coalesced into one or two more distinctive and consistent responses (the putative M response and the putative H reflex) in both groups. Both the initial evoked responses and the time course of their maturation returned sooner in the ChABC group than in the untreated (UT) group. The reinnervated Sol and TA were coactivated during treadmill locomotion during downslope, level, and upslope walking throughout the study period in both UT and ChABC-treated rats. By 10 wk after nerve transection and repair, locomotor activity in Sol, but not TA, had returned to its pretransection pattern. There was an increased reliance on central control of Sol activation across slopes for both groups as interpreted from elevated prestance Sol EMG activity that was no longer modulated with slope. Limb length and orientation during locomotion were similar to those observed prior to nerve injury during upslope walking only in the ChABC-treated rats. Thus treatment of cut nerves with ChABC leads to improvements in functional recovery.

BDNF-TrkB and proBDNF-p75NTR/Sortilin Signaling Pathways are Involved in Mitochondria-Mediated Neuronal Apoptosis in Dorsal Root Ganglia after Sciatic Nerve Transection

2020 ◽  
Vol 19 (1) ◽  
pp. 66-82 ◽  
Author(s):  
Xianbin Wang ◽  
Wei Ma ◽  
Tongtong Wang ◽  
Jinwei Yang ◽  
Zhen Wu ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Signaling Pathways ◽  
Nerve Injury ◽  
Sensory Neurons ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Neuronal Apoptosis ◽  
Nerve Transection ◽  
Sciatic Nerve Transection

Background: Brain-Derived Neurotrophic Factor (BDNF) plays critical roles during development of the central and peripheral nervous systems, as well as in neuronal survival after injury. Although proBDNF induces neuronal apoptosis after injury in vivo, whether it can also act as a death factor in vitro and in vivo under physiological conditions and after nerve injury, as well as its mechanism of inducing apoptosis, is still unclear. Objective: In this study, we investigated the mechanisms by which proBDNF causes apoptosis in sensory neurons and Satellite Glial Cells (SGCs) in Dorsal Root Ganglia (DRG) After Sciatic Nerve Transection (SNT). Methods: SGCs cultures were prepared and a scratch model was established to analyze the role of proBDNF in sensory neurons and SGCs in DRG following SNT. Following treatment with proBDNF antiserum, TUNEL and immunohistochemistry staining were used to detect the expression of Glial Fibrillary Acidic Protein (GFAP) and Calcitonin Gene-Related Peptide (CGRP) in DRG tissue; immunocytochemistry and Cell Counting Kit-8 (CCK8) assay were used to detect GFAP expression and cell viability of SGCs, respectively. RT-qPCR, western blot, and ELISA were used to measure mRNA and protein levels, respectively, of key factors in BDNF-TrkB, proBDNF-p75NTR/sortilin, and apoptosis signaling pathways. Results: proBDNF induced mitochondrial apoptosis of SGCs and neurons by modulating BDNF-TrkB and proBDNF-p75NTR/sortilin signaling pathways. In addition, neuroprotection was achieved by inhibiting the biological activity of endogenous proBDNF protein by injection of anti-proBDNF serum. Furthermore, the anti-proBDNF serum inhibited the activation of SGCs and promoted their proliferation. Conclusion: proBDNF induced apoptosis in SGCs and sensory neurons in DRG following SNT. The proBDNF signaling pathway is a potential novel therapeutic target for reducing sensory neuron and SGCs loss following peripheral nerve injury.

scholarly journals Time course of neuroanatomical and functional recovery after bilateral pudendal nerve injury in female rats

2007 ◽  
Vol 293 (5) ◽  
pp. F1614-F1621 ◽  
Author(s):  
Margot S. Damaser ◽  
Mary K. Samplaski ◽  
Mansi Parikh ◽  
Dan Li Lin ◽  
Soujanya Rao ◽  
...  
Keyword(s):  
Nerve Injury ◽  
Functional Recovery ◽  
Pudendal Nerve ◽  
Light And Electron Microscopy ◽  
Female Rats ◽  
Nerve Degeneration ◽  
Nerve Transection ◽  
External Urethral Sphincter ◽  
Nerve Crush ◽  
Distal Nerve

The pudendal nerve innervates the external urethral sphincter (EUS) and is among the tissues injured during childbirth, which may lead to symptoms of stress urinary incontinence (SUI). To understand the mechanisms of injury and repair, urethral leak-point pressure (LPP) was measured 4 days, 2 wk, or 6 wk after bilateral pudendal nerve crush. Morphometric changes in the distal nerve and EUS were examined by light and electron microscopy. To determine whether recovery resulted from pudendal neuroregeneration, LPP was measured before and after pudendal nerve transection 2 wk after nerve crush. LPP was significantly decreased 4 days after pudendal nerve crush compared with sham-injured animals as well as 2 or 6 wk after nerve crush. LPP was not significantly different 2 or 6 wk after nerve crush compared with sham-injured animals, suggesting that urethral function had returned to normal. Four days after pudendal nerve crush, the EUS branch of the pudendal nerve distal to the injury site showed evidence of nerve degeneration and the EUS appeared disrupted. Two weeks after nerve crush, the distal nerve and EUS both showed evidence of both nerve degeneration and recovery. Two weeks after nerve crush, LPP was significantly decreased after nerve transection. Six weeks after nerve injury, evidence of neuroregeneration was observed in the pudendal nerve and the EUS. This study has demonstrated that functional recovery and neuroregeneration are significant 2 wk after nerve crush, although by anatomical assessment, recovery appears incomplete, suggesting that 2 wk represents an early time point of initial neuroregeneration.

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.

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