Spinal Cord Injury: Neuropathology well away from the lesion contributes to dysfunction

Denman Undergraduate Research Forum 2nd Place in Health Professions- Laboratory/CellularSpinal cord injury (SCI) results in sensory and motor dysfunction and ultimately physical, psychological, and financial burden. Unfortunately, the cure for SCI remains elusive and intensive neurorehabilitation produces only modest functional gains. The most abundant cells in the CNS, astrocytes, are essential to neuronal function through bidirectional communication, support, and maintenance of the blood-brain / blood-spinal cord barrier (BBB/BSCB). Studies of the injury epicenter have identified activation and proliferation of astrocytes in the production of a glial scar as an essential component of the innate post- injury response. While this response is well characterized, the role of astrocytes in remote regions is controversial and less understood. Studies suggest a decreasing gradient of astrocyte reactivity moving away from the epicenter, however studies extending into the lumbar cord display conflicting results. To determine the remote astrocytic response, we examined the time course of astrocyte dysfunction in the intermediate grey matter of the lumbar spinal cord at 7, 14, 21, and 42 days post injury (dpi) using C56BL/6 mice after a moderate (75 kilodyne) midthoracic contusion injury. We examined the BSCB in detail by labeling vasculature with tomato lectin, astrocytes with GFAP, and their interface with aquaporin-4. Additionally, we used the cell adhesion molecule, ICAM-1, to determine the presence of active trafficking of peripheral cells into the CNS as well as Iba-1 to examine microglia/macrophage morphology. GFAP was seen to be significantly upregulated at 7 dpi and remained slightly elevated through 42 dpi. Microglia/macrophages displayed a reactive phenotype and increased expression through 42 dpi with biphasic peaks at 7 and 21 dpi. ICAM-1 showed slight increases at 14 dpi, indicating active trafficking of peripheral immune cells into the cord, and AQP4 was localized to the vasculature at all time points with an apparent increase in co-labeling at 7 dpi. These results provide valuable insight into astrocyte dysfunction in key locomotor regions essential for functional recovery following SCI as well as focus for future research to help improve the benefits of activity based therapies like treadmill training.NIH 1 R01 NS074882-01A1 (DMB)NIH HHSN271200800036C (CBSCR)Foundation for Physical Therapy (TDF)Florence P. Kendall Doctoral ScholarshipPromotion of Doctoral Studies Level IA five-year embargo was granted for this item.Academic Major: Neuroscienc