Pre and Post-Injury Treatment with PSCMA Prevents Symptoms of Chronic Traumatic Encephalopathy

Introduction: It is not well understood why repetitive head injury causes the behavioral and pathologic sequelae associated with Chronic Traumatic Encephalopathy (CTE). Cellular prion protein (PrPC) is associated with several neurodegenerative diseases including Alzheimer’s disease and Creutzfeldt-Jakob disease. There has been indication in the literature that PrPC is involved in traumatic brain injury (TBI). In this study, we demonstrate that inhibiting PrPC via administration of PSCMA prevents the pathology and behavior associated with CTE after repetitive head injury.

Methods: Experimental groups consisted of control and experimental PrPC wild-type (WT) mice. Experimental animals were treated with PSCMA either pre or post-impaction. Acquisition swims and probe trials were completed over a 5-day period with Morris water maze (MWM) testing. Bilateral close-head injury consisted of a 10-day daily impaction with appropriate unimpacted controls. All animals were allowed to recover for 6 weeks. Reversal swims and probe trials in the MWM were conducted over a 5-day period.

Results: Baseline latencies to reach the hidden platform were similar for all pre-impaction mice. Untreated post-impaction mice were found to have significantly increased latencies to reach the location of the hidden platform. Interestingly, latencies observed in pre and post-impaction PSCMA-treated mice were significantly reduced compared to impacted mice that did not receive PSCMA. Untreated mice had clear learning deficits following impactions, whereas PSCMA mice did not.

Conclusion : Pre and post-impaction treatment with PSCMA in a murine model of CTE had a protective effect against the negative pathologic and cognitive sequelae associated with CTE. Mouse behavior in injured PSCMA-treated mice was very similar to uninjured controls. This study provides evidence that PrPc is essential in the generation of CTE and PSCMA is a highly efficacious pharmacologic agent for both prophylactic and therapeutic management of CTE.