Cortical Spreading Depression Denotes Concussion Injury

Cortical spreading depression (CSD) has been described after moderate-to-severe traumatic brain injury (TBI). It is uncertain, however, whether CSD occurs after mild, concussive TBI and whether it relates to brain pathology and functional outcome. Male C57BL6/J mice (n = 62) were subjected to closed head TBI with a 25 g weight (n = 11), 50 g weight (n = 45), or sham injury (n = 6). Laser Doppler flowmetry and optical intrinsic signal imaging were used to determine cerebral blood flow dynamics after concussive CSD. Functional deficits were assessed at baseline, 2 h, 24 h, and 48 h. TUNEL and Prussian blue staining were used to determine cell death and presence of cerebral microbleeds at 48 h. No CSD was observed in mice subjected to a 25 g weight drop whereas 58.9% of mice subjected to a 50 g weight drop developed a CSD. Mice with concussive CSD displayed significantly greater numbers of apoptotic cell profiles in the ipsilesional hemisphere compared with mice without a CSD that underwent the same 50 g weight drop paradigm (p < 0.05, each). All investigated animals had at least one cerebral microbleed (range 1 to 24). Compared with mice without a CSD, mice with a CSD had significantly more microbleeds in the traumatized hemisphere (p < 0.05, each) and showed impaired functional recovery (p < 0.05). Incidence of CSD after mild TBI depended on impact severity and was associated with histological and behavioral outcomes. These observations indicate that concussive CSD may serve as viable marker for concussion severity and provide novel avenues for outcome prediction and therapeutic decision making.