Upregulation of TRESK Channels Contributes to Motor and Sensory Recovery after Spinal Cord Injury

TWIK (tandem-pore domain weak inward rectifying K+)-related spinal cord K+ channel (TRESK), a member of the two-pore domain K+ channel family, is abundantly expressed in dorsal root ganglion (DRG) neurons. It is well documented that TRESK expression is changed in several models of peripheral nerve injury, resulting in a shift in sensory neuron excitability. However, the role of TRESK in the model of spinal cord injury (SCI) has not been fully understood. This study investigates the role of TRESK in a thoracic spinal cord contusion model, and in transgenic mice overexpressed with the TRESK gene (TGTRESK). Immunostaining analysis showed that TRESK was expressed in the dorsal and ventral neurons of the spinal cord. The TRESK expression was increased by SCI in both dorsal and ventral neurons. TRESK mRNA expression was upregulated in the spinal cord and DRG isolated from the ninth thoracic (T9) spinal cord contusion rats. The expression was significantly upregulated in the spinal cord below the injury site at acute time points (6, 24, and 48 h) after SCI (p < 0.05). In addition, TRESK expression was markedly increased in DRGs below and adjacent to the injury site. TRESK was expressed in inflammatory cells. In addition, the number and fluorescence intensity of TRESK-positive neurons increased in the dorsal and ventral horns of the spinal cord after SCI. TGTRESK SCI mice showed faster paralysis recovery and higher mechanical threshold compared to wild-type (WT)-SCI mice. TGTRESK mice showed lower TNF-α concentrations in the blood than WT mice. In addition, IL-1β concentration and apoptotic signals in the caudal spinal cord and DRG were significantly decreased in TGTRESK SCI mice compared to WT-SCI mice (p < 0.05). These results indicate that TRESK upregulated following SCI contributes to the recovery of paralysis and mechanical pain threshold by suppressing the excitability of motor and sensory neurons and inflammatory and apoptotic processes.

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Cortical neuroprosthesis-mediated functional ipsilateral control of locomotion in rats with incomplete spinal cord injury

10.1101/2021.06.18.448959 ◽

2021 ◽

Author(s):

Elena Massai ◽

Marco Bonizzato ◽

Marina Martinez

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Causal Link ◽

Cortical Activation ◽

Motor Tasks ◽

Thoracic Spinal Cord ◽

Thoracic Spinal ◽

Cord Injury ◽

Hindlimb Movement

Control of voluntary limb movement is predominantly attributed to the contralateral motor cortex. Nevertheless, increasing evidence suggests the involvement of ipsilateral cortical networks in this process. Ipsilateral control particularly emerges in motor tasks requiring bilateral coordination, which is an essential characteristic of locomotion. Here, we combined a unilateral thoracic spinal cord injury (SCI) with a cortical neuroprosthetic intervention that uncovered a functional role of the ipsilateral cortex in rat movement. In all rats, after SCI, ipsilesional cortex excitation promoted a bilateral synergy, whereby the elevation of the contralateral foot was complemented by ipsilateral hindlimb extension. In two animals, we found that stimulation of a medial cortical sub-region modulated ipsilateral hindlimb flexion. Ipsilateral cortical stimulation delivered after SCI alleviated multiple locomotor and postural deficits. These results establish a causal link between cortical activation and a remarkably fine and proportional ipsilateral control of hindlimb movement, a potential target for future neuroprosthetic technology.

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Intraspinal AAV Injections Immediately Rostral to a Thoracic Spinal Cord Injury Site Efficiently Transduces Neurons in Spinal Cord and Brain

Molecular Therapy — Nucleic Acids ◽

10.1038/mtna.2013.34 ◽

2013 ◽

Vol 2 ◽

pp. e108 ◽

Cited By ~ 20

Author(s):

Michelle C Klaw ◽

Chen Xu ◽

Veronica J Tom

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Thoracic Spinal Cord ◽

Injury Site ◽

Thoracic Spinal ◽

Cord Injury

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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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