Abstract

Background Spinal cord injury (SCI) affects locomotion and quality of life. Two spinal cord stimulation approaches are currently under investigation for restoring standing and walking following SCI: epidural spinal cord stimulation (ESCS) and intraspinal microstimulation (ISMS). In ESCS, electrodes are placed on the dura mater and in ISMS, ultrafine wires are inserted into the cord. These modalities likely activate the locomotor regions in the ventral horn through different pathways. Objective The goal of this study is to examine the difference in the distribution of neuronal activation and the type of neurons activated by ESCS and ISMS. Methods The first step was to establish the needed immunohistochemical (IHC) staining protocols. Domestic pigs were divided into naïve (n=2) and positive control (n=1) groups. The naïve control animals were anesthetized for 5 hrs. The positive control animal was anesthetized for 2 hrs and injected with hypertonic saline in hindlimb muscles. The animals were then euthanized, and the spinal cord removed for IHC analysis. Antibodies against cFos, a maker of neuronal activation, and NeuN, a neuronal marker were used. Results Preliminary results indicate that ESCS activates neurons in the dorsal horn with scattered activation in the intermediate and ventral regions. ISMS primarily activates neurons in the intermediate and ventral regions where locomotor-related networks reside. Significance To the best of our knowledge, this is the first time the type and sites of activation of ESCS and ISMS are investigated. This will provide a foundational understanding of the mechanism of action of these stimulation modalities.

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