Anti-Inflammatory Potential of Stearidonic Acid Ethanolamide in a Model of Mild Traumatic Brain Injury in Mice

Chronic neuroinflammation is recognized as a pivotal mechanism responsible for secondary damage following mild traumatic brain injury (mTBI), underscoring the critical need for therapeutic strategies capable of mitigating this pathological process. This study evaluated the anti-inflammatory properties of stearidonic acid ethanolamide (SDEA, C20H33NO2). The findings indicate that mTBI triggers persistent neuroinflammation, which is correlated with cognitive deficits. A ten-day treatment regimen with SDEA at 10 mg/kg/day facilitated the restoration of cognitive abilities and suppressed the neuroinflammatory cascade in a mouse model. Memory impairments and anxiety-like behaviors were quantified through behavioral testing. Immunohistochemical techniques were employed to examine alterations in Iba-1-positive microglia and nNOS-positive cells within the cortical and hippocampal regions (CA1 and DG). The expression profiles of pro- and anti-inflammatory markers (IL1β, IL6, TNFα, CD68, CD206) were analyzed via reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Furthermore, an in vitro model of LPS-induced inflammation in SIM-A9 microglial cells was utilized to investigate the impact of SDEA on the production of cytokines, reactive oxygen species (ROS), nitric oxide (NO), and nitrites. Integrative analysis of in vivo and in vitro data showed that SDEA: (1) improved behavioral deficits by reducing anxiety and improving working memory; (2) suppressed pro-inflammatory microglial activation and nNOS-positive cells; (3) lowered pro-inflammatory cytokine, ROS, NO, and nitrite concentrations; and (4) enhanced CD206 marker expression in the cerebral cortex. These collective findings underscore the therapeutic potential of SDEA for traumatic CNS injuries.