Celecoxib in a preclinical model of repetitive mild traumatic brain injury: hippocampal learning deficits persist with inflammatory and excitotoxic neuroprotection
We sought to investigate molecular pathways involved in neuroinflammation in response to celecoxib treatment in a mouse model of subconcussive mTBI. 15 mTBIs were delivered over 23 days in adult male C57BL/6J mice in one of four groups (control; celecoxib without impact; celecoxib with impact, and vehicle with impact). Mice were assessed for cognitive function 48 hours and 3 months following the final mTBI. Morris Water Maze (MWM) testing revealed impaired hippocampal spatial learning performance in the celecoxib treatment group compared with control in the acute phase, with no improvement in celecoxib treatment compared with control at chronic testing. mRNA analysis of the cerebral cortex and hippocampus in the genes Mapt, Gfap, Aif1, Gria1, Tardbp, Tnf and Nefl revealed expression change indicating significant improvement in microglial activation, inflammation, excitotoxicity, and neurodegeneration at chronic measurement. These data suggest that in the acute phase following injury, celecoxib provided ineffective treatment against neuroinflammation and exacerbated clinical cognitive disturbance. Moreover, while there was evidence of neuroprotective alleviation of mTBI pathophysiology at chronic measurement, there remained no benefit in clinical features. The results of this study provide insight into the role of COX during inflammation and in the use of COX mediating drugs in the treatment of mTBI symptoms.