Optogenetic spinal stimulation promotes new axonal growth and skilled forelimb recovery in rats with sub-chronic cervical spinal cord injury.

Autor:	Mondello SE; Department of Rehabilitation Medicine, University of Washington, Seattle, WA 98195, United States of America.; Center for Neurotechnology, Seattle, WA 98195, United States of America., Young L; Department of Rehabilitation Medicine, University of Washington, Seattle, WA 98195, United States of America., Dang V; Department of Rehabilitation Medicine, University of Washington, Seattle, WA 98195, United States of America., Fischedick AE; Department of Rehabilitation Medicine, University of Washington, Seattle, WA 98195, United States of America., Tolley NM; Department of Rehabilitation Medicine, University of Washington, Seattle, WA 98195, United States of America.; Center for Neurotechnology, Seattle, WA 98195, United States of America., Wang T; Department of Rehabilitation Medicine, University of Washington, Seattle, WA 98195, United States of America., Bravo MA; Department of Rehabilitation Medicine, University of Washington, Seattle, WA 98195, United States of America.; Center for Neurotechnology, Seattle, WA 98195, United States of America., Lee D; Department of Rehabilitation Medicine, University of Washington, Seattle, WA 98195, United States of America., Tucker B; Department of Rehabilitation Medicine, University of Washington, Seattle, WA 98195, United States of America., Knoernschild M; Department of Rehabilitation Medicine, University of Washington, Seattle, WA 98195, United States of America., Pedigo BD; Department of Rehabilitation Medicine, University of Washington, Seattle, WA 98195, United States of America.; Center for Neurotechnology, Seattle, WA 98195, United States of America., Horner PJ; Center for Neuroregeneration, Department of Neurological Surgery, Houston Methodist Research Institute, Houston, TX 77030, United States of America., Moritz CT; Department of Rehabilitation Medicine, University of Washington, Seattle, WA 98195, United States of America.; Center for Neurotechnology, Seattle, WA 98195, United States of America.; Department of Electrical and Computer Engineering, University of Washington, Seattle, WA 98195, United States of America.; Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195, United States of America.
Jazyk:	angličtina
Zdroj:	Journal of neural engineering [J Neural Eng] 2023 Sep 12; Vol. 20 (5). Date of Electronic Publication: 2023 Sep 12.
DOI:	10.1088/1741-2552/acec13
Abstrakt:	Objective. Spinal cord injury (SCI) leads to debilitating sensorimotor deficits that greatly limit quality of life. This work aims to develop a mechanistic understanding of how to best promote functional recovery following SCI. Electrical spinal stimulation is one promising approach that is effective in both animal models and humans with SCI. Optogenetic stimulation is an alternative method of stimulating the spinal cord that allows for cell-type-specific stimulation. The present work investigates the effects of preferentially stimulating neurons within the spinal cord and not glial cells, termed 'neuron-specific' optogenetic spinal stimulation. We examined forelimb recovery, axonal growth, and vasculature after optogenetic or sham stimulation in rats with cervical SCI. Approach. Adult female rats received a moderate cervical hemicontusion followed by the injection of a neuron-specific optogenetic viral vector ipsilateral and caudal to the lesion site. Animals then began rehabilitation on the skilled forelimb reaching task. At four weeks post-injury, rats received a micro-light emitting diode (µLED) implant to optogenetically stimulate the caudal spinal cord. Stimulation began at six weeks post-injury and occurred in conjunction with activities to promote use of the forelimbs. Following six weeks of stimulation, rats were perfused, and tissue stained for GAP-43, laminin, Nissl bodies and myelin. Location of viral transduction and transduced cell types were also assessed. Main Results. Our results demonstrate that neuron-specific optogenetic spinal stimulation significantly enhances recovery of skilled forelimb reaching. We also found significantly more GAP-43 and laminin labeling in the optogenetically stimulated groups indicating stimulation promotes axonal growth and angiogenesis. Significance. These findings indicate that optogenetic stimulation is a robust neuromodulator that could enable future therapies and investigations into the role of specific cell types, pathways, and neuronal populations in supporting recovery after SCI. (Creative Commons Attribution license.)
Databáze:	MEDLINE
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