Post‐TBI administration of DHA selectively suppresses pro‐inflammatory and promotes resolving microglial activation (877.5)

Abstract

We investigated the manifestation of neuroinflammation after traumatic brain injury (TBI) and the efficacy of docosahexaenoic acid (DHA) in reducing neuroinflammation. TBI was induced by cortical contusion injury in Sprague Dawley rats. Either DHA (16 mg/kg in DMSO) or vehicle DMSO (1 ml/kg) was administered interperitonially at 5 min after TBI, followed by a daily dose for 3‐21 days. TBI triggered activation of microglia, detected by increase of Iba1 positively stained microglial cells in cortical tissues at 3‐21 days post‐TBI. The neuroinflammatory response was further characterized by an increased expression of the pro‐inflammatory marker CD16/32 in Iba1+ microglia at 3‐7 days post‐TBI. The Iba1+ microglia surrounded cortical neurons exhibiting ER stress. In contrast, DHA reduced acute neuronal damage and ER stress at 3 days post‐TBI. DHA‐treated TBI brains also showed significantly less CD16/32+ and Iba1+ microglial population, but increased CD206+/Iba1+ microglial (phagocytic) population. In summary, this study demonstrated that TBI induces a profound neuroinflammatory response that is characterized by pro‐inflammatory microglial activation. ER stress‐associated inflammation may play a role in the activation of microglia. Post‐TBI administration of DHA reduces neuronal damage, ER stress, and promotes the resolving microglial activation.Grant Funding Source: Supported by Univ. of Pitt. startup funds, endowed Chair Professorship (DS) & VA RR&D grant (CED).