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

IF 3.7 3区 医学 Q2 ENGINEERING, BIOMEDICAL Journal of neural engineering Pub Date : 2023-09-12 DOI:10.1088/1741-2552/acec13
Sarah E Mondello, Lisa Young, Viet Dang, Amanda E Fischedick, Nicholas M Tolley, Tian Wang, Madison A Bravo, Dalton Lee, Belinda Tucker, Megan Knoernschild, Benjamin D Pedigo, Philip J Horner, Chet Moritz
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引用次数: 1

Abstract

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.

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光遗传学脊髓刺激促进亚慢性颈脊髓损伤大鼠新的轴突生长和熟练的前肢恢复。
目的:脊髓损伤(SCI)导致衰弱的感觉运动缺陷,极大地限制了生活质量。这项工作旨在发展对如何最好地促进SCI后功能恢复的机制理解。脊髓电刺激是一种很有前途的方法,对SCI动物模型和人类都有效。光遗传学刺激是一种刺激脊髓的替代方法,允许细胞类型特异性刺激。目前的工作研究了优先刺激脊髓内神经元而不是神经胶质细胞的影响,称为“神经元特异性”光遗传学脊髓刺激。我们检测了宫颈SCIA大鼠在光遗传学或假刺激后的前肢恢复、轴突生长和血管系统。方法。成年雌性大鼠接受中度宫颈半刺激,然后在病变部位同侧和尾部注射神经元特异性光遗传学病毒载体。然后,动物开始进行熟练的前肢伸展任务的康复。在损伤后四周,大鼠接受微发光二极管(µLED)植入物,以光遗传学刺激尾脊髓。刺激在受伤后六周开始,与促进前肢使用的活动同时进行。刺激六周后,对大鼠进行灌注,并对组织进行GAP-43、层粘连蛋白、尼斯小体和髓鞘染色。还评估了病毒转导的位置和转导的细胞类型。主要结果:我们的研究结果表明,神经元特异性光遗传学脊髓刺激显著提高了熟练前肢伸展的恢复能力。我们还发现,在光遗传学刺激组中,GAP-43和层粘连蛋白标记显著增加,表明刺激促进轴突生长和血管生成。意义。这些发现表明,光遗传学刺激是一种强大的神经调节剂,可以使未来的治疗和研究特定细胞类型、途径和神经元群体在支持SCI后恢复中的作用。
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来源期刊
Journal of neural engineering
Journal of neural engineering 工程技术-工程:生物医学
CiteScore
7.80
自引率
12.50%
发文量
319
审稿时长
4.2 months
期刊介绍: The goal of Journal of Neural Engineering (JNE) is to act as a forum for the interdisciplinary field of neural engineering where neuroscientists, neurobiologists and engineers can publish their work in one periodical that bridges the gap between neuroscience and engineering. The journal publishes articles in the field of neural engineering at the molecular, cellular and systems levels. The scope of the journal encompasses experimental, computational, theoretical, clinical and applied aspects of: Innovative neurotechnology; Brain-machine (computer) interface; Neural interfacing; Bioelectronic medicines; Neuromodulation; Neural prostheses; Neural control; Neuro-rehabilitation; Neurorobotics; Optical neural engineering; Neural circuits: artificial & biological; Neuromorphic engineering; Neural tissue regeneration; Neural signal processing; Theoretical and computational neuroscience; Systems neuroscience; Translational neuroscience; Neuroimaging.
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