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Cellular Changes in Injured Rat Spinal Cord Following Electrical Brainstem Stimulation

Department of Neurological Surgery, University of Miami, 1095 NW 14th Terr, Miami, FL 33136, USA
Miami Project to Cure Paralysis, University of Miami, 1095 NW 14th Terr., Miami, FL 33136, USA
Author to whom correspondence should be addressed.
Brain Sci. 2019, 9(6), 124;
Received: 6 May 2019 / Revised: 23 May 2019 / Accepted: 27 May 2019 / Published: 28 May 2019
(This article belongs to the Special Issue Surgery for Spine Disease and Intractable Pain)
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. View Full-Text
Keywords: neuromodulation; inflammation; serotonin; neural progenitor cell; deep brain stimulation neuromodulation; inflammation; serotonin; neural progenitor cell; deep brain stimulation
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Jermakowicz, W.J.; Sloley, S.S.; Dan, L.; Vitores, A.; Carballosa-Gautam, M.M.; Hentall, I.D. Cellular Changes in Injured Rat Spinal Cord Following Electrical Brainstem Stimulation. Brain Sci. 2019, 9, 124.

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