Deep cerebellar stimulation enhances cognitive recovery after prefrontal traumatic brain injury in rodent.

Functional outcome following traumatic brain injury (TBI) varies greatly, with approximately half of those who survive suffering long-term motor and cognitive deficits despite contemporary rehabilitation efforts. We have previously shown that deep brain stimulation (DBS) of the lateral cerebellar nucleus (LCN) enhances rehabilitation of motor deficits that result from brain injury. The objective of the present study was to evaluate the efficacy of LCN DBS on recovery from rodent TBI that uniquely models the injury location, chronicity and resultant cognitive symptoms observed in most human TBI patients. We used controlled cortical impact (CCI) to produce an injury that targeted the medial prefrontal cortex (mPFC-CCI) bilaterally, resulting in cognitive deficits. Unilateral LCN DBS electrode implantation was performed 6 weeks post-injury. Electrical stimulation started at week eight post-injury and continued for an additional 4 weeks. Cognition was evaluated using baited Y-maze, novel object recognition task and Barnes maze. Post-mortem analyses, including Western Blot and immunohistochemistry, were conducted to elucidate the cellular and molecular mechanisms of recovery. We found that mPFC-CCI produced significant cognitive deficits compared to pre-injury and naïve animals. Moreover, LCN DBS treatment significantly enhanced the long-term memory process and executive functions of applying strategy. Analyses of post-mortem tissues showed significantly greater expression of CaMKIIα, BDNF and p75