POST-CONCUSSION SYNDROME: VALIDATING ALLODYNIA AND TRANSIENT MOTOR DEFICITS IN A RAT MODEL OF REPETITIVE CLOSED HEAD INJURY (rCHI).
CM Macolino1,2, MB Elliott2
1Jefferson Graduate School of Biomedical Sciences, Thomas Jefferson University, Philadelphia, PA. 2Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA.
More than 300,000 sports-related concussions occur each year in the United States. Concussion is associated with headache and transient motor deficits. We hypothesized that rats undergoing repetitive closed head injury (rCHI), a model of concussion, will show persistent periorbital (PO) and paw allodynia, as well as increased transient motor deficits compared to incision-only and sCHI groups. We propose increases in markers for a nociceptive neuropeptide, astrogliosis and traumatic axonal injury will support the effects of CHI on behavior. Male Sprague-Dawley rats received incision-only, single CHI or repetitive CHI. Von Frey mechanical sensory testing for allodynia and rotarod testing for motor deficits were evaluated at baseline, day 3 and day 7 after last impact. Immunohistological changes were evaluated using Calcitonin Gene Related Peptide (CGRP), β-Amyloid Precursor Protein (β-APP) and Glial Fibrillary Acidic Protein (GFAP). sCHI and rCHI rats had reduced periorbital and forepaw (p<.05, respectively) thresholds three days after last impact. Reduced rCHI PO thresholds persisted seven days after last impact (p<.0001) while sCHI PO thresholds returned to baseline by day seven. Rotarod testing at accelerated speeds revealed increased motor deficits in sCHI rats on day three (p<0.01) that resolve by day seven while rCHI rats have increased deficits on day three and persist to day seven (p<0.05). Increases in CGRP in the TNC were present in sCHI and rCHI groups seven days after injury. Increases in β-APP and GFAP were present in the sensorimotor cortex. In conclusion, allodynia and motor deficits persist up to seven days after last impact in rCHI rats compared to sCHI and incision-only control rats, corresponding with histopathological markers for nociception, gliosis and traumatic axonal injury.