179 Stem Progenitor Cell Proliferation in the Brainstem After Spinal Cord Injury: A Potential Target for Therapeutic Intervention Distant From the Site of Injury

Abstract

INTRODUCTION: Though there has been an increasing number of clinical trials focused on modulating stem/progenitor cell proliferation in the spinal cord after spinal cord injury (SCI), little is known about the acute response of stem/progenitor cells in supraspinal structures. We hypothesized that the signals stimulating stem/progenitor cell proliferation in the spinal cord after SCI activate similar responses in supraspinal regions because pathways injured in the spinal cord have their targets or sources in the brain. METHODS: We employed a mouse model of SCI, bromodeoxyuridine (BrdU) labeling of cells in S-phase, and co-labeling of markers of astrocytes, microglia, glial/oligodendrocyte precursor cells, and neuronal lineages to characterize the proliferative response within the brainstem of C57BL/6J mice 96 hours after a thoracic SCI. The extent of SCI and white matter (WM) spared was quantified by labeling of beta amyloid precursor protein and eriochrome cyanine R staining, respectively. RESULTS: Compared to sham-operated mice, there was a significant increase (3-fold; p < 0.01) in BrdU-labeled cells in the ventral-caudal medulla of injured mice. This response was consistent with the extent of SCI and primarily in WM tracts (57%) and the inferior olive (41%; IO). Co-labeling with cell-specific markers indicated that this response is glial (i.e., NG-2+ glial/oligodendrocyte precursor cells and GFAP+ astrocytes) with the largest increase in the number of BrdU-labeled cells occurring in the IO (6-fold increase; p < 0.01). Notably, there were no BrdU-labeled cells that co-labeled with markers of microglia or neuronal lineages. CONCLUSIONS: Our results demonstrate a stem/progenitor cell response within days of SCI that occurs distant from the injury site, notably in brainstem structures involved in motor learning and coordination. These findings highlight an acute response of glial/oligodendrocyte precursor cells in the brainstem as a potential target for future studies and therapeutic intervention after SCI.