scholarly journals Neural Stem Cell Transplantation Improves Locomotor Function in Spinal Cord Transection Rats Associated with Nerve Regeneration and IGF-1 R Expression

2019 ◽  
Vol 28 (9-10) ◽  
pp. 1197-1211 ◽  
Author(s):  
Xiao-Ming Zhao ◽  
Xiu-Ying He ◽  
Jia Liu ◽  
Yang Xu ◽  
Fei-Fei Xu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Spinal Nerve ◽  
Nerve Fibers ◽  
Spinal Cord Transection ◽  
Type I ◽  
Locomotor Function ◽  
Cord Injury

Transplantation of neural stem cells (NSCs) is a potential strategy for the treatment of spinal cord transection (SCT). Here we investigated whether transplanted NSCs would improve motor function of rats with SCT and explored the underlying mechanism. First, the rats were divided into sham, SCT, and NSC groups. Rats in the SCT and NSC groups were all subjected to SCT in T10, and were administered with media and NSC transplantation into the lesion site, respectively. Immunohistochemistry was used to label Nestin-, TUNEL-, and NeuN-positive cells and reveal the expression and location of type I insulin-like growth factor receptor (IGF-1 R). Locomotor function of hind limbs was assessed by Basso, Beattie, Bresnahan (BBB) score and inclined plane test. The conduction velocity and amplitude of spinal nerve fibers were measured by electrophysiology and the anatomical changes were measured using magnetic resonance imaging. Moreover, expression of IGF-1 R was determined by real-time polymerase chain reaction and Western blotting. The results showed that NSCs could survive and differentiate into neurons in vitro and in vivo. SCT-induced deficits were reduced by NSC transplantation, including increase in NeuN-positive cells and decrease in apoptotic cells. Moreover, neurophysiological profiles indicated that the latent period was decreased and the peak-to-peak amplitude of spinal nerve fibers conduction was increased in transplanted rats, while morphological measures indicated that fractional anisotropy and the number of nerve fibers in the site of spinal cord injury were increased after NSC transplantation. In addition, mRNA and protein level of IGF-1 R were increased in the rostral segment in the NSC group, especially in neurons. Therefore, we concluded that NSC transplantation promotes motor function improvement of SCT, which might be associated with activated IGF-1 R, especially in the rostral site. All of the above suggests that this approach has potential for clinical treatment of spinal cord injury.

scholarly journals Intraspinal Injection of Platelet-Rich Plasma Promotes Regeneration of the Spinal Cord and Improves Locomotor Function by Modulating the Apoptosis and the Wnt Signaling Pathways

2021 ◽  
Author(s):  
Zahra Behroozi ◽  
Fatemeh Ramezani ◽  
farinaz Nasirinezhad
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Wnt Signaling ◽  
Motor Function ◽  
Platelet Rich Plasma ◽  
Wnt Signaling Pathway ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Locomotor Function ◽  
Cord Injury

Abstract Background: There are complex mechanisms for reducing intrinsic repair ability and neuronal regeneration following spinal cord injury (SCI). Platelet-rich plasma (PRP) is a rich source of growth factors and has been used to stimulate regeneration of peripheral nerves in degenerationtive diseases. However, only a few studies have investigated the effects of PRP on the SCI models. We examined whether PRP derived from human umbilical cord blood (HUCB-PRP) could recover motor function in animals with spinal cord injury. We also investigate the role of Wnt signaling pathway.Methods: Ault male Wistar rats were randomly divided into 6 groups (n=60) as control, sham, SCI, vehicle (SCI+platelet-poor plasma), PRP2day (SCI+injection 2 days after SCI) and PRP14day (SCI+injection 14 days after SCI). SCI was performed at the T12-T13 level. BBB tests were done weekly after injury for six weeks. caspase3 expression was determined using the Immunohistochemistry technique. The expression of GSK3β, Tau and MAG were determined using the Western blot technique. Data were analyzed by PRISM & SPSS software. Results: PRP injected animals showed a higher locomotor function recovery than those in the SCI group (p<0.0001). The level of caspase3, GSK3β and CSF- Tau reduced and MAG level in the spinal cord increased by injection of HUCB-PRP in animals with spinal cord injury. Conclusions: Injection of HUCB-PRP enhanced hind limb locomotor performance by modulation of caspase3, GSK3β, tau and MAG expression. Using HUCB-PRP could be a new therapeutic option for recovering the motor function and axonal regeneration after spinal cord injury.

scholarly journals A meta-analysis of exosome in the treatment of spinal cord injury

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 1043-1060
Author(s):  
Hanxiao Yi ◽  
Yang Wang
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Sequential Analysis ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Trial Sequential Analysis ◽  
Therapeutic Effects ◽  
Locomotor Function ◽  
Cord Injury

Abstract Context There are no recommended therapeutic agents for acute spinal cord injury (SCI) due to the pathophysiological complexity of the injury. Objective The objective of this study is to investigate the efficacy of various exosomes and potential factors impacting the efficacy of exosomes. Methods We searched the PubMed, EMBASE, Web of Science, Medline, Scopus, and Cochrane Library databases to systematically collect articles comparing the locomotor function of SCI rodents undergoing exosome treatment and untreated SCI rodents. No language was preferred. Results Pooled analysis revealed that the locomotor function recovery of SCI rodents receiving exosomes was greatly improved (583 rats, 3.12, 95% CI: 2.56–3.67, p < 0.01; 116 mice, 2.46, 95% CI: 1.20–3.72, p < 0.01) compared to those of control rodents. The trial sequential analysis demonstrated the findings of the meta-analysis with the cumulative Z-curve crossing the upper monitoring boundary for the benefit and reaching the adjusted required information size. However, the origin of the exosome, SCI model, and administration method determined the therapeutic effect to some extent. Conclusions Despite the proven therapeutic effects of exosomes on SCI rodents, the results should be interpreted cautiously considering the diversity in vivo and in vitro in relation to future trials.

scholarly journals Ecto-domain phosphorylation promotes functional recovery from spinal cord injury

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Kenji Suehiro ◽  
Yuka Nakamura ◽  
Shuai Xu ◽  
Youichi Uda ◽  
Takafumi Matsumura ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Enhanced Recovery ◽  
Neuronal Cell ◽  
Cell Production ◽  
Locomotor Function ◽  
Neuronal Precursor Cells ◽  
Cord Injury ◽  
Adult Spinal Cord

Abstract Inhibition of Nogo-66 receptor (NgR) can promote recovery following spinal cord injury. The ecto-domain of NgR can be phosphorylated by protein kinase A (PKA), which blocks activation of the receptor. Here, we found that infusion of PKA plus ATP into the damaged spinal cord can promote recovery of locomotor function. While significant elongation of cortical-spinal axons was not detectable even in the rats showing enhanced recovery, neuronal precursor cells were observed in the region where PKA plus ATP were directly applied. NgR1 was expressed in neural stem/progenitor cells (NSPs) derived from the adult spinal cord. Both an NgR1 antagonist NEP1-40 and ecto-domain phosphorylation of NgR1 promote neuronal cell production of the NSPs, in vitro. Thus, inhibition of NgR1 in NSPs can promote neuronal cell production, which could contribute to the enhanced recovery of locomotor function following infusion of PKA and ATP.

scholarly journals Jia-Ji Electro-Acupuncture Improves Locomotor Function With Spinal Cord Injury by Regulation of Autophagy Flux and Inhibition of Necroptosis

2021 ◽  
Vol 14 ◽  
Author(s):  
Yin Hongna ◽  
Tian Hongzhao ◽  
Li Quan ◽  
Feng Delin ◽  
Liu Guijun ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Acupuncture Treatment ◽  
Spinal Cord Tissue ◽  
Autophagy Flux ◽  
Nissl Staining ◽  
Microscopy Imaging ◽  
Locomotor Function ◽  
Cord Injury

Jia-Ji electro-acupuncture (EA) has been widely applied in clinic to exhibit curative effects on spinal cord injury (SCI). However, its underlying mechanisms leading to improvement of motor function after SCI remain unclear. Allen’s method was made by NYU Impactor M-III equipment to create the SCI rats model. Rats were randomly divided into four groups: Sham (only laminectomy), Model (SCI group), EA (SCI + Jia-Ji EA treatment), EA + CQ (SCI + Jia-Ji EA treatment + inhibitor chloroquine). Basso-Beattie-Bresnahan assessment showed improvement of hind limb motor function after Jia-Ji electro-acupuncture treatment. Histological change of injured spinal cord tissue was alleviated after treatment, observed by hematoxylin-eosin and Nissl staining. The mRNA and protein expression levels of RIPK1, RIPK3 and MLKL were decreased in EA group. Besides, the increased expression of LC3 and reduced expression of P62 after treatment compared with Model group, confirmed that Jia-Ji electro-acupuncture could enhance the autophagy flux. Electron microscopy imaging showed increasing the number of lysosomes, autophagosomes, and autolysosomes after Jia-Ji electro-acupuncture treatment. Furthermore, inhibition of lysosome function with CQ led to partly eliminate the effect of EA on reducing necroptosis. These data make the case that Jia-Ji electro-acupuncture treatment may improve locomotor function by promoting autophagy flux and inhibiting necroptosis.

scholarly journals Mettl14-mediated m6A modification modulates neuron apoptosis during the repair of spinal cord injury by regulating the transformation from pri‐mir‐375 to miR-375

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Haoyu Wang ◽  
Jing Yuan ◽  
Xiaoqian Dang ◽  
Zhibin Shi ◽  
Wenrui Ban ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Critical Region ◽  
Cell Model ◽  
Spinal Cord Tissue ◽  
Spinal Cord Neurons ◽  
Cord Injury ◽  
Neuron Apoptosis

Abstract Background Spinal cord injury (SCI) is a disabling disorder, resulting in neurological impairments. This study investigated the mechanism of methyltransferase-like 14 (Mettl14) on apoptosis of spinal cord neurons during SCI repair by mediating pri-microRNA (miR) dependent N6-methyladenosine (m6A) methylation. Methods The m6A content in total RNA and Mettl14 levels in spinal cord tissues of SCI rats were detected. Mettl14 expression was intervened in SCI rats to examine motor function, neuron apoptosis, and recovery of neurites. The cell model of SCI was established and intervened with Mettl14. miR-375, related to SCI and positively related to Mettl14, was screened out. The expression of miR-375 and pri-miR-375 after Mettl14 intervention was detected. The expression of pri-miR-375 combined with DiGeorge critical region 8 (DGCR8) and that modified by m6A was detected. Furthermore, the possible downstream gene and pathway of miR-375 were analysed. SCI cell model with Mettl14 intervention was combined with Ras-related dexamethasone-induced 1 (RASD1)/miR-375 intervention to observe the apoptosis. Results Mettl14 level and m6A content in spinal cord tissue were significantly increased. After Mettl14 knockdown, the injured motor function was restored and neuron apoptosis was reduced. In vitro, Mettl14 silencing reduced the apoptosis of SCI cells; miR-375 was reduced and pri-miR-375 was increased; miR-375 targeted RASD1. Silencing Mettl14 inactivated the mTOR pathway. The apoptosis in cells treated with silencing Mettl14 + RASD1/miR-375 was inhibited. Conclusions Mettl14-mediated m6A modification inhibited RASD1 and induced the apoptosis of spinal cord neurons in SCI by promoting the transformation of pri-miR-375 to mature miR-375.

Fibrin scaffolds embedded with sonic hedgehog/chitosan microspheres for recovery of spinal cord injury in rats

2020 ◽  
Vol 10 (3) ◽  
pp. 437-445 ◽  
Author(s):  
Wenjing Yang ◽  
Zhe Wang ◽  
Jingxin Zhang ◽  
Kaiyuan Yang ◽  
Cong Lu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Biological Activity ◽  
Motor Function ◽  
Sonic Hedgehog ◽  
Nerve Fibers ◽  
Injury Site ◽  
Cord Injury ◽  
Recovery Of Motor Function

Sonic hedgehog (SHH) has been shown to exert a protection on promoting the spinal cord injury (SCI) recovery, but it can’t remain with its biological activity and sustained release at the injury site for long-term application. Herein, fibrin scaffolds embedded with SHH-loaded chitosan (CS) microspheres (SHH/CS) were synthesized and applied to provide protection and regeneration for complete transected spinal cord in rats. Characteristics of fibrin scaffolds embedded with SHH/CS microspheres, histological studies, immunohistochemistry staining, Western Blotting and recovery of motor function were conducted after implantation, respectively. Result showed that SHH maintained its biological activity and continued to act at the injury site, and the fibrin scaffolds embedded with SHH/CS microspheres could protect neurons and reduce apoptosis in the in vivo study, it also promoted some nerve fibers cross the spinal cord injury area. Moreover, the scaffolds improved partial motor function of double-hindlimb on a macro level. Overall, the fibrin scaffolds embedded with SHH/CS microspheres showed more satisfactory effect on nerve regeneration, tissue cavities prevention and motor function improvement, compared to fibrin scaffolds with SHH directly encapsulated into or fibrin scaffolds alone.

scholarly journals Photobiomodulation inhibits the activation of neurotoxic microglia and astrocytes by inhibiting Lcn2/JAK2-STAT3 crosstalk after spinal cord injury in male rats

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Xuankang Wang ◽  
Xin Li ◽  
Xiaoshuang Zuo ◽  
Zhuowen Liang ◽  
Tan Ding ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Male Rats ◽  
In Vitro Experiments ◽  
Post Injury ◽  
Stat3 Pathway ◽  
Cord Injury ◽  
Recovery Of Motor Function

Abstract Background Neurotoxic microglia and astrocytes begin to activate and participate in pathological processes after spinal cord injury (SCI), subsequently causing severe secondary damage and affecting tissue repair. We have previously reported that photobiomodulation (PBM) can promote functional recovery by reducing neuroinflammation after SCI, but little is known about the underlying mechanism. Therefore, we aimed to investigate whether PBM ameliorates neuroinflammation by modulating the activation of microglia and astrocytes after SCI. Methods Male Sprague–Dawley rats were randomly divided into three groups: a sham control group, an SCI + vehicle group and an SCI + PBM group. PBM was performed for two consecutive weeks after clip-compression SCI models were established. The activation of neurotoxic microglia and astrocytes, the level of tissue apoptosis, the number of motor neurons and the recovery of motor function were evaluated at different days post-injury (1, 3, 7, 14, and 28 days post-injury, dpi). Lipocalin 2 (Lcn2) and Janus kinase-2 (JAK2)-signal transducer and activator of transcription-3 (STAT3) signaling were regarded as potential targets by which PBM affected neurotoxic microglia and astrocytes. In in vitro experiments, primary microglia and astrocytes were irradiated with PBM and cotreated with cucurbitacin I (a JAK2-STAT3 pathway inhibitor), an adenovirus (shRNA-Lcn2) and recombinant Lcn2 protein. Results PBM promoted the recovery of motor function, inhibited the activation of neurotoxic microglia and astrocytes, alleviated neuroinflammation and tissue apoptosis, and increased the number of neurons retained after SCI. The upregulation of Lcn2 and the activation of the JAK2-STAT3 pathway after SCI were suppressed by PBM. In vitro experiments also showed that Lcn2 and JAK2-STAT3 were mutually promoted and that PBM interfered with this interaction, inhibiting the activation of microglia and astrocytes. Conclusion Lcn2/JAK2-STAT3 crosstalk is involved in the activation of neurotoxic microglia and astrocytes after SCI, and this process can be suppressed by PBM.

Timing and duration of anti–α4β1 integrin treatment after spinal cord injury: effect on therapeutic efficacy

2009 ◽  
Vol 11 (5) ◽  
pp. 575-587 ◽  
Author(s):  
Jennifer C. Fleming ◽  
Feng Bao ◽  
Yuhua Chen ◽  
Eilis F. Hamilton ◽  
Laura E. Gonzalez-Lara ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Mechanical Allodynia ◽  
Myeloperoxidase Activity ◽  
Antibody Treatment ◽  
Locomotor Function ◽  
Cord Injury ◽  
Tissue Sparing

Object After spinal cord injury (SCI) leukocytes infiltrate the injured cord, causing significant damage and further impairment of functional recovery. The leukocyte integrin α4β1 is crucial for their entry. The authors previously demonstrated that an anti-α4 monoclonal antibody (mAb) treatment attenuates leukocyte infiltration, improves motor and autonomic function, and reduces neuropathic pain when administered at 2 hours and 24 hours after SCI. Methods The authors conducted 2 preclinical studies: the first determined effects of treatment commencing at 6 hours, a clinically relevant time after injury, and the second examined effects of long-lasting treatment (28 days) on neurological recovery after SCI, as current clinically used anti-inflammatory monoclonal antibodies have such longevity. In the first study (timing study), rats were treated with anti-α4 or control mAb (intravenously) at 6 hours and 48 hours after moderate (35 g) thoracic compression SCI. Effects on intraspinal inflammation and oxidative injury were assessed at 3 and 7 days after SCI; motor function and pain were examined for 6 weeks. In the second study (duration study), anti-α4 mAb was administered starting 2 hours after SCI and subsequently every 3 days for 4 weeks (total of 8 doses), using a schedule of decreasing doses to resemble the pharmacodynamics of long-lasting antibodies used clinically. Motor function and pain were examined for 6 weeks. Lesions were assessed for tissue sparing and inflammation at 6 weeks by histological examination and MR imaging. Results Anti-α4 mAb treatment at 6 hours and 48 hours after SCI (timing study) significantly decreased neutrophil and monocyte/macrophage influx at 3 days by 36% and 20%, respectively, but had no effect by at 7 days after SCI. Antibody treatment significantly reduced intraspinal myeloperoxidase activity by 48% and lipid peroxidation by 27% at 3 days post-injury. The treatment did not improve locomotor function but reduced mechanical allodynia elicited from the trunk and hind paw by ~ 50% at 3–6 weeks after SCI. In contrast, long-term mAb treatment commencing at 2 hours after SCI (duration study) significantly improved locomotor function at 2–6 weeks after SCI, (mean BBB scores ± SE: treated rats, 8.3 ± 0.16; controls, 7.3 ± 0.2 at 6 weeks). At 3–6 weeks, mAb treatment decreased mechanical allodynia elicited from the trunk and hind paw by ~ 55%. This recovery correlated with 30% more myelin-containing white matter in treated rats than controls at 6 weeks. The lesion cavity was smaller in the treated rats when assessed by both histological (−37%) and imaging (−50%) methods. The accumulation of ED1-immunoreactive microglia/macrophages at the lesion was similar in treated and control rats. Conclusions Although delayed treatment reduced intraspinal inflammation and pain, motor function was not improved, revealing decreased efficacy at the more clinically feasibly treatment onset. Long-term anti-α4 mAb treatment starting 2 hours after SCI improved neurological outcomes, with tissue sparing near the lesion and no impairment of the late immune response to injury. These findings reveal no disadvantage of long-lasting immunosuppression by the treatment but show that efficacy depends upon very early delivery.

Photobiomodulation Inhibits the Activation of Neurotoxic Microglia and Astrocytes Through Inhibiting the Crosstalk of Lcn2/JAK2-STAT3 after Spinal Cord Injury in Rats

2021 ◽  
Author(s):  
Xuankang Wang ◽  
Xin Li ◽  
Xiaoshuang Zuo ◽  
Zhuowen Liang ◽  
Zhe Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Janus Kinase ◽  
Vehicle Group ◽  
Lipocalin 2 ◽  
Stat3 Pathway ◽  
Cord Injury ◽  
Recovery Of Motor Function

Abstract BackgroundIn situ microglia and astrocytes begin to activate and participate in neuroinflammation after spinal cord injury (SCI), and the high expression of lipocalin 2 (Lcn2) and the activation of the Janus kinase-2 (JAK2)-signal transducer and activator of transcription-3 (STAT3) pathway promote the polarization of activated microglia and astrocytes towards the neurotoxic phenotype (M1 microglia and A1 astrocytes). We previously reported that photobiomodulation (PBM) can promote functional recovery by reducing neuroinflammation after SCI, but the mechanism of PBM on the microglia and astrocytes involved is still unclear. Therefore, the purpose of this study was to explore the role of the Lcn2 and JAK2-STAT3 pathways in the activation of M1 and A1 and the mechanism by which PBM may play a therapeutic role.MethodsPBM intervention was performed every day after the SCI model was established, and the activation of microglia and astrocytes was observed at different time points post injury (1, 3, 7, 14, 28 dpi). The level of tissue apoptosis, the number of surviving neurons, the recovery of motor function, the level of Lcn2 and the activation of JAK2-STAT3 were evaluated in the PBM group and the vehicle group. M1 and A1 cells were irradiated with PBM in vitro, and the JAK2-STAT3 pathway inhibitor cucurbitacin I, adenovirus transfection and recombinant Lcn2 protein were cotreated with PBM to explore the mechanism of the activation of M1 and A1 and the underlying effect of PBM.ResultsPBM inhibited the activation of neurotoxic microglia and astrocytes, decreased secondary inflammation and tissue apoptosis, increased the number of neurons retained, and promoted the recovery of motor function after SCI. The upregulation of Lcn2 and the activation of the JAK2-STAT3 pathway after SCI were suppressed by PBM. In vitro experiments also proved that PBM can inhibit the activation of M1 microglia and A1 astrocytes, and the effect is related to the level of Lcn2 and the activation of the JAK2-STAT3 pathway.ConclusionThe crosstalk of Lcn2/JAK2-STAT3 is involved in the activation of neurotoxic microglia and astrocytes after SCI, and this process can be alleviated by PBM.

scholarly journals Locomotor-related V3 interneurons initiate and coordinate muscles spasms after spinal cord injury

2019 ◽  
Vol 121 (4) ◽  
pp. 1352-1367 ◽  
Author(s):  
Shihao Lin ◽  
Yaqing Li ◽  
Ana M. Lucas-Osma ◽  
Krishnapriya Hari ◽  
Marilee J. Stephens ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Muscle Activation ◽  
Muscle Activation Patterns ◽  
Cord Injury ◽  
Sensory Evoked ◽  
Sensory Activation

Spinal cord injury leads to a devastating loss of motor function and yet is accompanied by a paradoxical emergence of muscle spasms, which often involve complex muscle activation patterns across multiple joints, reciprocal muscle timing, and rhythmic clonus. We investigated the hypothesis that spasms are a manifestation of partially recovered function in spinal central pattern-generating (CPG) circuits that normally coordinate complex postural and locomotor functions. We focused on the commissural propriospinal V3 neurons that coordinate interlimb movements during locomotion and examined mice with a chronic spinal transection. When the V3 neurons were optogenetically activated with a light pulse, a complex coordinated pattern of motoneuron activity was evoked with reciprocal, crossed, and intersegmental activity. In these same mice, brief sensory stimulation evoked spasms with a complex pattern of activity very similar to that evoked by light, and the timing of these spasms was readily reset by activation of V3 neurons. Given that V3 neurons receive abundant sensory input, these results suggest that sensory activation of V3 neurons is alone sufficient to generate spasms. Indeed, when we silenced V3 neurons optogenetically, sensory evoked spasms were inhibited. Also, inhibiting general CPG activity by blocking N-methyl-d-aspartate (NMDA) receptors inhibited V3 evoked activity and associated spasms, whereas NMDA application did the opposite. Furthermore, overwhelming the V3 neurons with repeated optogenetic stimulation inhibited subsequent sensory evoked spasms, both in vivo and in vitro. Taken together, these results demonstrate that spasms are generated in part by sensory activation of V3 neurons and associated CPG circuits. NEW & NOTEWORTHY We investigated whether locomotor-related excitatory interneurons (V3) play a role in coordinating muscle spasm activity after spinal cord injury (SCI). Unexpectedly, we found that these neurons not only coordinate reciprocal motor activity but are critical for initiating spasms, as well. More generally, these results suggest that V3 neurons are important in initiating and coordinating motor output after SCI and thus provide a promising target for restoring residual motor function.

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