Striatal damage may underlie motor learning impairment following experimental mild traumatic brain injury in mice.

The Renin-Angiotensin system (RAS) has receptors in key brain areas, including the striatum, and has been implicated in traumatic brain injury (TBI) outcomes through involvement in inflammation and oxidative stress. To date, whether striatal RAS dysregulation alongside inflammatory response and oxidative stress underlie mild TBI-related motor coordination and learning impairments remain to be explored. Herein, we employed a weight drop model to induce mild TBI (mTBI) in mice and investigate striatal damage at 72 h after the trauma. mTBI mice displayed significant decrease in the motor learning index and increase in the latency to fall in the rotarod compared with sham controls. In parallel, mTBI-mice had increased expression of RAS classical arm components AT1 and AT2 receptors along with a decrease in RAS counter-regulatory component Mas receptor in the ipsilateral striatum. The neurotrophic factor GDNF increased and the chemokine CX3CL1 decreased in the ipsilateral striatum while TNF-α enhanced in the contralateral striatum at 72 h after mTBI. Higher lipid peroxidation (TBARS) levels were found in both ipsilateral and contralateral striatum of mTBI mice compared with sham mice. We provided original evidence that changes in RAS, inflammatory, neurotrophic and oxidative stress responses in the striatum may contribute to motor dysfunction following acute mTBI.