Remodeling of lumbar motor circuitry remote to a thoracic spinal cord injury promotes locomotor recovery

Retrogradely-transported neurotrophin signaling plays an important role in regulating neural circuit specificity. Here we investigated whether targeted delivery of neurotrophin-3 (NT-3) to lumbar motoneurons (MNs) caudal to a thoracic (T10) contusive spinal cord injury (SCI) could modulate dendritic patterning and synapse formation of the lumbar MNs. In vitro, Adeno-associated virus serotype two overexpressing NT-3 (AAV-NT-3) induced NT-3 expression and neurite outgrowth in cultured spinal cord neurons. In vivo, targeted delivery of AAV-NT-3 into transiently demyelinated adult mouse sciatic nerves led to the retrograde transportation of NT-3 to the lumbar MNs, significantly attenuating SCI-induced lumbar MN dendritic atrophy. NT-3 enhanced sprouting and synaptic formation of descending serotonergic, dopaminergic, and propriospinal axons on lumbar MNs, parallel to improved behavioral recovery. Thus, retrogradely transported NT-3 stimulated remodeling of lumbar neural circuitry and synaptic connectivity remote to a thoracic SCI, supporting a role for retrograde transport of NT-3 as a potential therapeutic strategy for SCI.

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RGMa inhibition promotes axonal growth and recovery after spinal cord injury

The Journal of Cell Biology ◽

10.1083/jcb.200508143 ◽

2006 ◽

Vol 173 (1) ◽

pp. 47-58 ◽

Cited By ~ 168

Author(s):

Katsuhiko Hata ◽

Masashi Fujitani ◽

Yuichi Yasuda ◽

Hideo Doya ◽

Tomoko Saito ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Axonal Growth ◽

Axonal Guidance ◽

Neural Tube Closure ◽

Cns Injury ◽

Thoracic Spinal Cord ◽

Thoracic Spinal ◽

Cord Injury

Repulsive guidance molecule (RGM) is a protein implicated in both axonal guidance and neural tube closure. We report RGMa as a potent inhibitor of axon regeneration in the adult central nervous system (CNS). RGMa inhibits mammalian CNS neurite outgrowth by a mechanism dependent on the activation of the RhoA–Rho kinase pathway. RGMa expression is observed in oligodendrocytes, myelinated fibers, and neurons of the adult rat spinal cord and is induced around the injury site after spinal cord injury. We developed an antibody to RGMa that efficiently blocks the effect of RGMa in vitro. Intrathecal administration of the antibody to rats with thoracic spinal cord hemisection results in significant axonal growth of the corticospinal tract and improves functional recovery. Thus, RGMa plays an important role in limiting axonal regeneration after CNS injury and the RGMa antibody offers a possible therapeutic agent in clinical conditions characterized by a failure of CNS regeneration.

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Effect of thoracic spinal cord injury on forelimb somatosensory evoked potential

Brain Research Bulletin ◽

10.1016/j.brainresbull.2021.05.005 ◽

2021 ◽

Author(s):

Angelo H. All ◽

Shiyu Luo ◽

Xiaogang Liu ◽

Hasan Al-Nashash

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Evoked Potential ◽

Somatosensory Evoked Potential ◽

Thoracic Spinal Cord ◽

Thoracic Spinal ◽

Cord Injury

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Emergency decompression and stabilization of 1st thoracic spinal cord injury and sacral fracture in a Covid-19 patient: A case report

International Journal of Surgery Case Reports ◽

10.1016/j.ijscr.2021.105670 ◽

2021 ◽

Vol 81 ◽

pp. 105670

Author(s):

Achmad Jadi Didy Surachman ◽

Yanuarso ◽

Danar Lukman Akbar

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Case Report ◽

Sacral Fracture ◽

Thoracic Spinal Cord ◽

Thoracic Spinal ◽

Cord Injury

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Sonic Hedgehog modulates the inflammatory response and improves functional recovery after spinal cord injury in a thoracic contusion–compression model

European Spine Journal ◽

10.1007/s00586-021-06796-2 ◽

2021 ◽

Author(s):

Hao Zhang ◽

Alexander Younsi ◽

Guoli Zheng ◽

Mohamed Tail ◽

Anna-Kathrin Harms ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Sonic Hedgehog ◽

Functional Recovery ◽

Intrathecal Administration ◽

Neuroprotective Effects ◽

Thoracic Spinal Cord ◽

Shh Pathway ◽

Thoracic Spinal ◽

Cord Injury

Abstract Purpose The Sonic Hedgehog (Shh) pathway has been associated with a protective role after injury to the central nervous system (CNS). We, therefore, investigated the effects of intrathecal Shh-administration in the subacute phase after thoracic spinal cord injury (SCI) on secondary injury processes in rats. Methods Twenty-one Wistar rats were subjected to thoracic clip-contusion/compression SCI at T9. Animals were randomized into three treatment groups (Shh, Vehicle, Sham). Seven days after SCI, osmotic pumps were implanted for seven-day continuous intrathecal administration of Shh. Basso, Beattie and Bresnahan (BBB) score, Gridwalk test and bodyweight were weekly assessed. Animals were sacrificed six weeks after SCI and immunohistological analyses were conducted. The results were compared between groups and statistical analysis was performed (p < 0.05 was considered significant). Results The intrathecal administration of Shh led to significantly increased polarization of macrophages toward the anti-inflammatory M2-phenotype, significantly decreased T-lymphocytic invasion and significantly reduced resident microglia six weeks after the injury. Reactive astrogliosis was also significantly reduced while changes in size of the posttraumatic cyst as well as the overall macrophagic infiltration, although reduced, remained insignificant. Finally, with the administration of Shh, gain of bodyweight (216.6 ± 3.65 g vs. 230.4 ± 5.477 g; p = 0.0111) and BBB score (8.2 ± 0.2 vs. 5.9 ± 0.7 points; p = 0.0365) were significantly improved compared to untreated animals six weeks after SCI as well. Conclusion Intrathecal Shh-administration showed neuroprotective effects with attenuated neuroinflammation, reduced astrogliosis and improved functional recovery six weeks after severe contusion/compression SCI.

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