Research Scientist Stanford University Stanford, California
Rationale: Evidence has suggested that epilepsy contributes to cognitive impairment and anxiety behavior that are common in patients with post-traumatic epilepsy (PTE). Our previous results showed that TrkB receptor partial agonist can reduce epileptogenesis following cortical injury by enhancing the function of interneurons. This study focused on whether a TrkB partial agonist can also help improve cognition and anxiety behavior through its effects on epilepsy and interneurons whose abnormal function is critically involved in cognitive dysfunction following traumatic brain injury (TBI). Methods: We used the controlled cortical impact (CCI) model of PTE in C57BL/6J mice that were treated intraperitoneally for two weeks beginning the day of injury with PTX BD4-3 (BD), a small molecule partial agonist at the BDNF TrkB receptor, using a a treatment regimen previously shown to significantly increase inhibitory interneuronal function (Gu et al., 2018). A series of behavioral tests, including open field, Y maze, novel object recognition, and elevated zero maze tests, were performed four to six weeks after the last BD treatment to evaluate the effects of BD on locomotor activity, spatial learning and memory, recognition memory, and anxiety behavior respectively. Results: Our results revealed that 1) CCI mice did not show any impairment in locomotor activity, and there was no effect of BD on locomotion; 2) CCI mice performed worse in Y maze and novel object recognition tests compared to sham control, and BD treatment significantly improved the performance of CCI mice in these tests; 3) in elevated zero maze test, percentage of time spent in exploring open arms was significantly increased from 20% in CCI mice treated with saline (n=14) to 27% in CCI mice treated with BD (n=14). Conclusions: These results suggest that chronic TrkB activation by a partial agonist after cortical injury can improve cognition and reduce anxiety in the CCI model of PTE. Funding: Please list any funding that was received in support of this abstract.: Supported by grant NS082644 from the NINDS (DP).