Cortical Spreading Depression Denotes Concussion Injury
Year: 2018
Type: article
Abstract: 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.
Source: Journal of Neurotrauma
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: ALS Association, Fondation Leducq, National Institutes of Health, U.S. Food and Drug Administration, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Institutional Career Development Core, The Harvard Clinical and Translational Science Center, Remodeling and recovery in the neurovascular unit, Non-invasive vagus nerve stimulation targeting cortical spreading depression in migrane prophylaxis, G4023803055, Biomarkers for Therapy of FSHD (U54), Silencing C9or72 with rAAV Mediated RNAi, Inhibiting axon degeneration in a mouse model of acute brain injury through deletion of Sarm1, G9000137960, G9000323787, Novel Therapeutics for FSHD, Neuroscience Resident Research Program
OpenAlex ID: W2860860357