Exercise plasma improves traumatic brain injury outcomes in mice.

Traumatic brain injury (TBI) is associated with pain and cognitive impairment although exercise may improve some adverse outcomes. We hypothesized that transfer of plasma derived from exercised mice would improve outcomes related to pain and memory after TBI. These studies used a concussive murine model of mild TBI. Plasma from sedentary or exercised mice was administered to TBI mice beginning 3 days after injuries. Mechanical nociceptive sensitization and descending control of nociception (DCN) were assessed. Object recognition memory and Y-maze were used to assess working memory. In addition, the spinal expression of Pdyn, Bdnf, Cxcl1 and Cxcl2 was measured 7 and 28 days after injuries. Levels of several candidate mediators of the exercise effects were measured in the transferred plasma. Mechanical allodynia following TBI recovered more quickly and DCN responses were partially preserved in animals receiving exercise plasma. Working memory was preserved in the same mice. The upregulation of spinal pain genes Pdyn and Bdnf was reduced by exercise plasma. Finally, exercise was associated with substantially higher plasma levels of TIMP2 and irisin. The present study suggests that developing therapies based on the administration of exercise plasma or its components may help reduce pain and cognitive loss after TBI.