Cellular Changes in Injured Rat Spinal Cord Following Electrical Brainstem Stimulation.

Walter J Jermakowicz,Ian D Hentall,Stephanie S Sloley,Melissa M Carballosa-Gautam,Alberto Vitores,Lia Dan

doi:10.3390/brainsci9060124

Walter J Jermakowicz, Ian D Hentall + Show 4 more

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https://doi.org/10.3390/brainsci9060124

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Journal: Brain sciences	Publication Date: May 28, 2019
Citations: 3	License type: CC BY 4.0

Affiliation: University of Miami, Neurological Surgery

Abstract

Spinal cord injury (SCI) is a major cause of disability and pain, but little progress has been made in its clinical management. Low-frequency electrical stimulation (LFS) of various anti-nociceptive targets improves outcomes after SCI, including motor recovery and mechanical allodynia. However, the mechanisms of these beneficial effects are incompletely delineated and probably multiple. Our aim was to explore near-term effects of LFS in the hindbrain’s nucleus raphe magnus (NRM) on cellular proliferation in a rat SCI model. Starting 24 h after incomplete contusional SCI at C5, intermittent LFS at 8 Hz was delivered wirelessly to NRM. Controls were given inactive stimulators. At 48 h, 5-bromodeoxyuridine (BrdU) was administered and, at 72 h, spinal cords were extracted and immunostained for various immune and neuroglial progenitor markers and BrdU at the level of the lesion and proximally and distally. LFS altered cell marker counts predominantly at the dorsal injury site. BrdU cell counts were decreased. Individually and in combination with BrdU, there were reductions in CD68 (monocytes) and Sox2 (immature neural precursors) and increases in Blbp (radial glia) expression. CD68-positive cells showed increased co-staining with iNOS. No differences in the expression of GFAP (glia) and NG2 (oligodendrocytes) or in GFAP cell morphology were found. In conclusion, our work shows that LFS of NRM in subacute SCI influences the proliferation of cell types implicated in inflammation and repair, thus providing mechanistic insight into deep brain stimulation as a neuromodulatory treatment for this devastating pathology.

Highlights

Spinal cord injury (SCI) involves widespread damage of local and distal neuronal networks [1,2].It is a major cause of disability worldwide, leading to impairments in motor and autonomic function as well as debilitating mechanical allodynia [3,4,5]
We have previously shown that low-frequency electrical stimulation (LFS) of the nucleus raphe magnus (NRM) or its primary midbrain afferent, the periaqueductal gray (PAG), improves functional and anatomic recovery from incomplete
We have previously shown that 2 h of NRM LFS three days after incomplete SCI restores cyclic adenosine monophosphate, an intracellular signaling molecule implicated in inflammation and repair, to pre-injury levels [19]

Summary

Introduction

Spinal cord injury (SCI) involves widespread damage of local and distal neuronal networks [1,2]. It is a major cause of disability worldwide, leading to impairments in motor and autonomic function as well as debilitating mechanical allodynia [3,4,5]. More recently, LFS of several of these targets and their inputs has received attention for its ability to improve functional outcomes in laboratory and clinical models of SCI [6,11,12,13,14,15]. A critical impediment to the clinical adoption of these treatments is lack of insight into the therapeutic mechanisms involved

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