A flexible electrode array for determining regions of motor function activated by epidural spinal cord stimulation in rats with spinal cord injury

Epidural stimulation of the spinal cord is a promising technique for the recovery of motor function after spinal cord injury.The key challenges within the reconstruction of motor function for paralyzed limbs are the precise control of sites and parameters of stimulation.To activate lower-limb muscles precisely by epidural spinal cord stimulation,we proposed a high-density,flexible electrode array.We determined the regions of motor function that were activated upon epidural stimulation of the spinal cord in a rat model with complete spinal cord,which was established by a transection method.For evaluating the effect of stimulation,the evoked potentials were recorded from bilateral lowerlimb muscles,including the vastus lateralis,semitendinosus,tibialis anterior,and medial gastrocnemius.To determine the appropriate stimulation sites and parameters of the lower muscles,the stimulation characteristics were studied within the regions in which motor function was activated upon spinal cord stimulation.In the vastus lateralis and medial gastrocnemius,these regions were symmetrically located at the lateral site of L1 and the medial site of L2 vertebrae segment,respectively.The tibialis anterior and semitendinosus only responded to stimulation simultaneously with other muscles.The minimum and maximum stimulation threshold currents of the vastus lateralis were higher than those of the medial gastrocnemius.Our results demonstrate the ability to identify specific stimulation sites of lower muscles using a high-density and flexible array.They also provide a reference for selecting the appropriate conditions for implantable stimulation for animal models of spinal cord injury.This study was approved by the Animal Research Committee of Southeast University,China(approval No.20190720001) on July 20,2019.     

不同年龄大鼠坐骨神经损伤后脊髓中神经生长导向因子Slit-1及Robo-2受体的表达变化

目的观察不同年龄大鼠坐骨神经损伤后,轴突导向因子Slit-1及其Robo-2受体在脊髓中的表达,以探讨不同年龄大鼠外周神经损伤后再生神经具有靶向性差异的可能机制。方法老年、成年和幼年大鼠各20只,建立左侧坐骨神经横断、硅胶管桥接模型。通过免疫荧光染色观察Slit-1蛋白和Robo-2受体在腰段脊髓中表达的变化,计算其荧光强度值,并进行统计学分析。结果伤后2周和4周,3组大鼠脊髓前角Slit蛋白均有较高表达,但各组间无显著差异。伤后2周和4周各组Robo-2受体表达均升高,其中老年鼠脊髓前角Robo-2受体表达明显高于成年和幼年组,差异有统计学意义(P0.05)。结论大鼠坐骨神经损伤后能刺激脊髓前角Slit-1高表达,不同年龄大鼠脊髓组织中Robo-2受体表达的差异可能决定了Slit-1在再生神经中的靶向性调节作用。     

Misdirection of regenerating axons and functional recovery following sciatic nerve injury in rats

Poor functional recovery found after peripheral nerve injury has been attributed to the misdirection of regenerating axons to reinnervate functionally inappropriate muscles. We applied brief electrical stimulation (ES) to the common fibular (CF) but not the tibial (Tib) nerve just prior to transection and repair of the entire rat sciatic nerve, to attempt to influence the misdirection of its regenerating axons. The specificity with which regenerating axons reinnervated appropriate targets was evaluated physiologically using compound muscle action potentials (M responses) evoked from stimulation of the two nerve branches above the injury site. Functional recovery was assayed using the timing of electromyography (EMG) activity recorded from the tibialis anterior (TA) and soleus (Sol) muscles during treadmill locomotion and kinematic analysis of hindlimb locomotor movements. Selective ES of the CF nerve resulted in restored M-responses at earlier times than in unstimulated controls in both TA and Sol muscles. Stimulated CF axons reinnervated inappropriate targets to a greater extent than unstimulated Tib axons. During locomotion, functional antagonist muscles, TA and Sol, were coactivated both in stimulated rats and in unstimulated but injured rats. Hindlimb kinematics in stimulated rats were comparable to untreated rats, but significantly different from intact controls. Selective ES promotes enhanced axon regeneration but does so with decreased fidelity of muscle reinnervation. Functional recovery is neither improved nor degraded, suggesting that compensatory changes in the outputs of the spinal circuits driving locomotion may occur irrespective of the extent of misdirection of regenerating axons in the periphery.     

Assessment of rat sciatic nerve function following acute implantation of high density utah slanted electrode array (25 electrodes/mm2) based on neural recordings and evoked muscle activity

Introduction: High density Utah slanted electrode arrays (HD‐USEAs) have been developed recently for intrafascicular access to submillimeter neural structures. Insertion of such high electrode density devices may cause nerve crush injury, counteracting the intended improved selective nerve fiber access. Methods: HD‐USEAs were implanted into sciatic nerves of anesthetized rats. Nerve function was assessed before and after HD‐USEA implantation by measuring changes in evoked muscle and nerve compound action potentials and single unit neuronal recordings. Results: Neural activity was recorded with over half of all implanted electrodes. Average decreases of 38%, 36%, and 13% in nerve, medial gastrocnemius, and tibialis anterior compound action potential amplitudes, respectively, were observed following array implantation. Only 1 of 8 implantations resulted in loss of all signals. Conclusions: These studies demonstrate that HD‐USEAs provide a useful neural interface without causing a nerve crush injury that would otherwise negate their use in acute preparations (<12 h). Muscle Nerve 50 : 417–424, 2014     

The effect of peripheral nerve injury on dorsal root potentials and on transmission of afferent signals into the spinal cord

The sciatic nerve adults rats was either cut and ligated or was crushed on one side. The response of the spinal cord to stimulation of the proximal part of the injured nerve was examined at various times after the lesion and compared to the effects of stimulating the intact nerve on the other side. During the first 10 days after nerve section the following measures were not affected: (i) the size of the input volley (compound action potential, CAP, measured on a dorsal root that carried sciatic nerve afferents (L5); (ii) the volley running in the dorsal columns; (iii) the dorsal root potential (DRP) evoked on neighbouring dorsal roots which do not contain sciatic afferents (L2 and L3); (iv) the post-synaptic volleys ascending in the spinal cord. However, by the fourth day after nerve section, there was a decrease of the DRP evoked on the ipsilateral L5 dorsal root by stimulation of the cut nerve. By 10 days this DRP had decreased by 50%. There was also a decrease in the DRP on the L5 root evoked by stimulation of the contralateral intact nerve. Crush lesions of the sciatic nerve did not produce DRP charge. Beginning 10–20 days after nerve cut, there was a decrease in the amplitude of the afferent CAP and of all the measures of central response to the afferent volley. We discuss the possibility that the loss of the DRP may be associated with a disinhibition which results in novel receptive fields which we observe in cord cells deafferented by the peripheral nerve section. The decrease of DRP and the appearance of novel receptive fields do not occur if the peripheral nerve is crushed rather than cut.     

Reinnervation of denervated muscle by transplantation of fetal spinal cord to transected sciatic nerve in the rat

When motor neurons in the spinal cord are destroyed, regeneration of motor axons and muscle reinnervation cannot be expected. We attempted reinnervation of the denervated muscle, i.e. motor unit reconstruction, using transplantation of the fetal spinal cord to the peripheral nerve. The sciatic nerve of an adult rat was resected for 20 mm, and a cavity was prepared using an autologous femoral vein at the distal stump of the nerve. The fetal spinal cord was then transplanted into the venous cavity. After 3–6 months, no voluntary muscle contraction was observed due to the absence of communication with the central nervous system. However, reinnervation of the muscles via the sciatic nerve by the transplanted spinal neurons was demonstrated electrophysiologically and histochemically. This suggested that a motor unit can be reconstructed by fetal spinal cord transplantation even if the original motor neurons in the spinal cord are not available.     

Glial cell reactions in the spinal cord after sensory nerve stimulation are associated with axonal injury

Astroglial and microglial reactions in the dorsal and ventral horns of the adult rat spinal cord were studied after graded electrical stimulation of the rat sciatic nerve and after topical application of mustard oil to the hindlimb foot. Antibodies to glial fibrillary acidic protein and complement receptor 3 (OX-42) were used as markers for astroglia and microglia, respectively. The results showed that electrical nerve stimulation resulted in increased immunoreactivity for GFAP and OX-42 in the spinal cord dorsal and ventral horns only after the use of stimulation strengths which were associated with nerve fiber degeneration in the stimulated nerve. Application of mustard oil to the foot caused no changes in GFAP or OX-42 immunoreactivity. These findings indicate that peripheral nerve stimulation in itself is insufficient to induce astroglial and microglial responses in the spinal cord. The signal(s) mediating these responses, regularly seen after nerve injury, are therefore most probably not related to the afferent barrage of action potentials evoked by the injury.     

Stimulation and recording from regenerated peripheral nerves through polyimide sieve electrodes

This paper describes the use of a new polyimide sieve electrode as a chronic neural interface to stimulate and record signals from regenerated peripheral nerves. Flexible thin polyimide electrodes were placed in silicone chambers and implanted between the severed ends of the sciatic nerve in rats. The sieve part of the interface has 281 round via holes of 40 microns diameter, with seven integrated recording-stimulating electrodes arranged around via holes. Axonal regeneration through the via holes was demonstrated by histological and physiological methods over a two to six month post-implantation period in all the rats. The regenerated nerves were organized in fascicles corresponding to the grid pattern of the via holes. Longitudinal sections showed myelinated fibers, with normal appearance and well developed myelin sheath, crossing the via holes. Stimulation of the regenerated nerve through the polyimide electrode evoked distal muscle and nerve responses similar in amplitude to those evoked by nerve stimulation with hook metal electrodes. The polyimide electrodes were useful for recording nerve action potentials in response to electrical stimulation of the distal regenerated nerve, and in response to functional sensory stimulation of several modalities.     

Pulsed electrical stimulation protects neurons in the dorsal root and anterior horn of the spinal cord after peripheral nerve injury

Most studies on peripheral nerve injury have focused on repair at the site of injury, but very few have examined the effects of repair strategies on the more proximal neuronal cell bodies. In this study, an approximately 10-mm-long nerve segment from the ischial tuberosity in the rat was transected and its proximal and distal ends were inverted and sutured. The spinal cord was subjected to pulsed electrical stimulation at T10 and L3, at a current of 6.5 m A and a stimulation frequency of 15 Hz, 15 minutes per session, twice a day for 56 days. After pulsed electrical stimulation, the number of neurons in the dorsal root ganglion and anterior horn was increased in rats with sciatic nerve injury. The number of myelinated nerve fibers was increased in the sciatic nerve. The ultrastructure of neurons in the dorsal root ganglion and spinal cord was noticeably improved. Conduction velocity of the sciatic nerve was also increased. These results show that pulsed electrical stimulation protects sensory neurons in the dorsal root ganglia as well as motor neurons in the anterior horn of the spinal cord after peripheral nerve injury, and that it promotes the regeneration of peripheral nerve fibers.     

压榨性坐骨神经损伤早期髓内炎症因子诱导型一氧化氮合酶及环氧合酶2表达的时序性

目的：研究炎症因子iNOS和COX-2在周围神经损伤早期的时空表达规律。方法：健康成年SD大鼠48只，随机分为正常组（n =8）、假手术组（n =8）和右侧坐骨神经压榨组(n =32)，实验组根据动物存活时间（6, 12, 24和72小时）再分为4组（每组n =8）,免疫组织化学方法检测L4～6脊髓内iNOS、COX-2的表达变化。结果：①正常组及假手术组动物L4～6脊髓内iNOS、COX-2呈低表达，两者比较差异无统计学意义(P >0.05)。②坐骨神经损伤后：损伤侧前、后角损伤侧iNOS和 COX-2免疫阳性染色强度随损伤时间逐渐增加，各时间点损伤侧前、后角分别与对侧和正常组相比差别有统计学意义(P <0.05)。结论：坐骨神经压榨损伤后早期iNOS和COX-2在脊髓内的表达呈上升趋势，提示iNOS和COX-2可能参与了周围神经损伤后炎性免疫反应的发生演进和神经性疼痛过程     

Peripheral nerve grafts after cervical spinal cord injury in adult cats

Peripheral nerve grafts (PNG) into the rat spinal cord support axon regeneration after acute or chronic injury, with synaptic reconnection across the lesion site and some level of behavioral recovery. Here, we grafted a peripheral nerve into the injured spinal cord of cats as a preclinical treatment approach to promote regeneration for eventual translational use. Adult female cats received a partial hemisection lesion at the cervical level (C7) and immediate apposition of an autologous tibial nerve segment to the lesion site. Five weeks later, a dorsal quadrant lesion was performed caudally (T1), the lesion site treated with chondroitinase ABC 2 days later to digest growth inhibiting extracellular matrix molecules, and the distal end of the PNG apposed to the injury site. After 4-20 weeks, the grafts survived in 10/12 animals with several thousand myelinated axons present in each graft. The distal end of 9/10 grafts was well apposed to the spinal cord and numerous axons extended beyond the lesion site. Intraspinal stimulation evoked compound action potentials in the graft with an appropriate latency illustrating normal axonal conduction of the regenerated axons. Although stimulation of the PNG failed to elicit responses in the spinal cord distal to the lesion site, the presence of c-Fos immunoreactive neurons close to the distal apposition site indicates that regenerated axons formed functional synapses with host neurons. This study demonstrates the successful application of a nerve grafting approach to promote regeneration after spinal cord injury in a non-rodent, large animal model.     

Spatiotemporal expression of inducible nitric oxide synthase and cyclooxygenase 2 in the spinal cord during early stage sciatic nerve crush injury

BACKGROUND: Previous studies have shown that inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) participate in inflammatory immune responses and neuropathic pain following peripheral nerve injury. However, few reports have addressed time-dependent expression of iNOS and COX-2 following peripheral nerve injury. OBJECTIVE: To investigate spatiotemporal expression of iNOS and COX-2 during early stage sciatic nerve crush injury.DESIGN, TIME AND SETTING: The randomized, controlled, animal experiment was performed at the Laboratory of Applied Anatomy, Department of Human Anatomy and Neurobiology, Central South University, China from September 2006 to September 2007.MATERIALS: Mouse anti-rat iNOS monoclonal antibody and goat anti-rat COX-2 monoclonal antibody (Transduction Laboratory, USA), as well as biotinylated rabbit anti-mouse lgG and biotinylated rabbit anti-goat IgG (Santa Cruz Biotechnology, USA) were used in the present study.METHODS: A total of 48 healthy, adult, Sprague Dawley rats were randomly assigned to three groups. In the model group (n = 32), crush injury to the right sciatic nerve was established using an artery clamp. The model group was further assigned to four subgroups according to survival time (6,12, 24, and 72 hours), respectively (n = 8). Sham surgery (n = 8) and normal control (n = 8) groups were also established.MAIN OUTCOME MEASURES: iNOS and COX-2 expression was detected in the L4-6 spinal cord with immunohistochemistry. Gray values of iNOS- and COX-2-postive cells in the anterior horn and posterior horn of spinal cord, as well as quantification of iNOS- and COX-2-positive cells in the anterior horn of spinal cord, were measured.RESULTS: iNOS and COX-2 expression gradually increased in the anterior horn and posterior horn of the spinal cord on the damaged side over time from 6 hours following sciatic nerve injury (P＜0.05) and peaked at 72 hours. Simultaneously, the number of iNOS- and COX-2-positive cells similarly increased in the anterior horn of spinal cord on the damaged side (P＜ 0.05).CONCLUSION: iNOS and COX-2 expression increased in the spinal cord during early stage sciatic nerve crush, which suggested that iNOS and COX-2 participate in occurrence and development of inflammatory immune responses following peripheral nerve injury.     

Craniocerebral injury promotes the repair of peripheral nerve injury

The increase in neurotrophic factors after craniocerebral injury has been shown to promote fracture healing. Moreover, neurotrophic factors play a key role in the regeneration and repair of peripheral nerve. However, whether craniocerebral injury alters the repair of peripheral nerve injuries remains poorly understood. Rat injury models were established by transecting the left sciatic nerve and using a free-fall device to induce craniocerebral injury. Compared with sciatic nerve injury alone after 6–12 weeks, rats with combined sciatic and craniocerebral injuries showed decreased sciatic functional index, increased recovery of gastrocnemius muscle wet weight, recovery of sciatic nerve ganglia and corresponding spinal cord segment neuron morphologies, and increased numbers of horseradish peroxidase-labeled cells. These results indicate that craniocerebral injury promotes the repair of peripheral nerve injury.     

Inhibitor of DNA binding 2 accelerates nerve regeneration after sciatic nerve injury in mice

Inhibitor of DNA binding 2 (Id2) can promote axonal regeneration after injury of the central nervous system. However, whether Id2 can promote axonal regeneration and functional recovery after peripheral nerve injury is currently unknown. In this study, we established a mouse model of bilateral sciatic nerve crush injury. Two weeks before injury, AAV9-Id2-3×Flag-GFP was injected stereotaxically into the bilateral ventral horn of lumbar spinal cord. Our results showed that Id2 was successfully delivered into spinal cord motor neurons projecting to the sciatic nerve, and the number of regenerated motor axons in the sciatic nerve distal to the crush site was increased at 2 weeks after injury, arriving at the tibial nerve and reinnervating a few endplates in the gastrocnemius muscle. By 1 month after injury, extensive neuromuscular reinnervation occurred. In addition, the amplitude of compound muscle action potentials of the gastrocnemius muscle was markedly recovered, and their latency was shortened. These findings suggest that Id2 can accelerate axonal regeneration, promote neuromuscular reinnervation, and enhance functional improvement following sciatic nerve injury. Therefore, elevating the level of Id2 in adult neurons may present a promising strategy for peripheral nerve repair following injury. The study was approved by the Experimental Animal Ethics Committee of Jinan University (approval No. 20160302003) on March 2, 2016.

Chinese Library Classification No. R456; R745; R364.3+3     

Effects of 660‐nm gallium–aluminum–arsenide low‐energy laser on nerve regeneration after acellular nerve allograft in rats

Purpose : The purpose of this study was to explore and discuss the effects of 660‐nm gallium–aluminum–arsenide low‐energy laser (GaAlAs LEL) irradiation on neural regeneration after acellular nerve allograft repair of the sciatic nerve gap in rats. Methods : Eight male and female Sprague–Dawley rats were used as nerve donors, and 32 healthy Wistar rats were randomly divided into four groups: normal control group, acellular rat sciatic nerve (ARSN) group, laser group, and autograft group. Twelve weeks after surgery, nerve conduction velocity, restoration rate of tibialis anterior wet muscle weight, myelinated nerve number, and calcitonin gene‐related peptide (CGRP) protein and mRNA expression of the spinal cord and muscle at the injury site were quantified and statistically analyzed. Results : Compared with the ARSN group, laser therapy significantly increased nerve conduction velocity, restoration rate of tibialis anterior wet muscle weight, myelinated nerve number, and CGRP protein and mRNA expression of the L₄ spinal cord at the injury site. Conclusions : These findings demonstrate that 660‐nm GaAlAs LEL therapy upregulates CGRP protein and mRNA expression of the L₄ spinal cord at the injury site and increases the rate of regeneration and target reinnervation after acellular nerve allograft repair of the sciatic nerve gap in rats. Low‐energy laser irradiation may be a useful, noninvasive adjunct for promoting nerve regeneration in surgically induced defects repaired with ARSN. Synapse 64:152–160, 2010. © 2009 Wiley‐Liss, Inc.     

肌电图在椎管内麻醉并发脊神经损害中的早期诊断价值

目的 探讨肌电图在椎管内麻醉并发脊神经损害中的早期诊断价值。方法 回顾性分析2016年9月-2021年2月临床诊断为椎管内麻醉并发脊神经损害的患者,行双下肢神经传导速度测定及针极肌电图检查,并对部分患者进行随访,采用0～5级肌力记录法对受损的神经所支配的肌肉进行临床肌力的恢复评估,对受损神经的复合肌肉动作电位(Compound muscle action potential, CMAP)/正常值比例与复查肌肉的肌力进一步做相关性分析。结果 41例椎管内麻醉患者行神经传导测定共检测运动及感觉神经329条,运动神经的CMAP降低60条,异常率为30.9%;感觉神经的感觉神经动作电位(Sensory nerve action potential, SNAP)降低12条,异常率为8.9%,且腓总神经、胫神经异常率(分别为41.7、29.7%)高于股神经异常率16.7%。41例患者共检测肌肉491块,异常肌肉331块,异常率67.4%,且低腰段及骶段脊神经支配的肌肉异常率(胫骨前肌、腓肠肌内侧头、低腰段及骶段脊旁肌异常率分别为79.7、82.9、81.5%)高于中腰段脊神经支配的肌肉(股四头肌内...     

Apelin inhibits motor neuron apoptosis in the anterior horn following acute spinal cord and sciatic nerve injuries

Rat models of acute spinal cord injury and sciatic nerve injury were established.Apelin expression in spinal cord tissue was determined.In normal rat spinal cords,apelin expression was visible;however,2 hours post spinal cord injury,apelin expression peaked.Apelin expression increased 1 day post ligation of the sciatic nerve compared with normal rat spinal cords,and peaked at 3 days.Apelin expression was greater in the posterior horn compared with the anterior horn at each time point when compared with the normal group.The onset of neuronal apoptosis was significantly delayed following injection of apelin protein at the stump of the sciatic nerve,and the number of apoptotic cells after injury was reduced when compared with normal spinal cords.Our results indicate that apelin is expressed in the normal spinal cord and central nervous system after peripheral nerve injury.Apelin protein can reduce motor neuron apoptosis in the spinal cord anterior horn and delay the onset of apoptosis.     

脊髓损伤大鼠远端神经元及骨骼肌变化的基础研究

目的观察脊髓损伤大鼠远端神经元及骨骼肌变化情况。方法 20只大鼠随机分为2组,每组10只,分别为假手术组和脊髓损伤组,假手术组行椎板切除术,脊髓损伤组行胸10完全脊髓损伤,在制成模型后1、2、4、12、24周观察大鼠坐骨神经-运动终板-内侧腓肠肌形态变化情况。结果脊髓损伤组电镜下坐骨神经术后12周有髓神经纤维髓鞘崩解,其板层结构清晰,有髓神经纤维髓鞘于术后24周模糊、碎裂髓鞘变多,12周后无髓神经纤维及薄髓增多;术后12周腓肠肌光镜下局部肌细胞多数模糊,但边界清楚,结缔组织增生明显,肌细胞核相对聚集;肌细胞于术后24周融合,融合细胞间有空隙,细胞核密集,结缔组织增生明显;术后12周电镜下运动终板突触前后及皱褶膜不可分辨,肌纤维明暗带清晰,突触结构紊乱,z线不连续,高倍镜下突触前后膜不可辨,突触皱褶未见,可见类圆形细小颗粒及突触小泡,肌板结构清晰。结论大鼠脊髓损伤后在损伤平面以下周围神经、运动终板、骨骼肌在形态上会发生规律性变化,12周后显著变化,24周后则毁损性改变。     

Brain injury in combination with tacrolimus promotes the regeneration of injured peripheral nerves

Both brain injury and tacrolimus have been reported to promote the regeneration of injured peripheral nerves. In this study, before transection of rat sciatic nerve, moderate brain contusion was (or was not) induced. After sciatic nerve injury, tacrolimus, an immunosup-pressant, was (or was not) intraperitoneally administered. At 4, 8 and 12 weeks after surgery, Masson's trichrome, hematoxylin-eosin, and toluidine blue staining results revealed that brain injury or tacrolimus alone or their combination alleviated gastrocnemius muscle atrophy and sciatic nerve fiber impairment on the experimental side, simultaneously improved sciatic nerve function, and increased gastrocnemius muscle wet weight on the experimental side. At 8 and 12 weeks after surgery, brain injury induction and/or tacrolimus treatment increased action potential amplitude in the sciatic nerve trunk. Horseradish peroxidase retrograde tracing revealed that the number of horseradish peroxidase-positive neurons in the anterior horn of the spinal cord was greatly increased. Brain injury in combination with tacrolimus ex-hibited better effects on repair of injured peripheral nerves than brain injury or tacrolimus alone. This result suggests that brain injury in combination with tacrolimus promotes repair of peripheral nerve injury.     

Regenerating motor bridge axons refine connections and synapse on lumbar motoneurons to bypass chronic spinal cord injury

To restore motor control after spinal cord injury requires reconnecting the brain with spinal motor circuits below the lesion. A bridge around the injury is an important alternative to promoting axon regeneration through the injury. Previously, we reported a novel motor bridge in rats. The thirteenth thoracic nerve was detached from the muscle it innervates and the cut end implanted caudally into the lumbar gray matter where motor bridge axons regenerate. In this study, we first determined that regenerating bridge axons project to spinal motor circuits. Stable projections were present in ventral motor laminae of the cord, including putative synapses directly on motoneurons, 2 months after insertion in the intact cord. At this time, earlier-forming dorsal horn projections were mostly eliminated. Regenerating axons were effective in evoking leg motor activity as early as 2 weeks. We next determined that bridge axons could regenerate caudal to a chronic injury. We hemisected the spinal cord at L2 and inserted the bridge nerve 1 month later at L5 and found ventral laminae projections similar to those in intact animals, including onto motoneurons directly. Finally, we determined that the bridge circuit could be activated by neural pathways rostral to its origin. For spinally hemisected animals, we electrically stimulated the rostral spinal cord and recorded evoked potentials from the bridge and, in turn, motor responses in the sciatic nerve. Our findings suggests that bridge motoneurons could be used by descending motor pathways as premotor interneurons to transmit neural signals to bypass a chronic spinal injury.