Effects of mild traumatic brain injury on phrenic and hypoglossal motor plasticity

With neurologic injury or disease, the central nervous system fights to retain function via compensatory mechanisms, including spontaneous injury-induced neuroplasticity. Just as in other neural systems, the neural system controlling breathing compensates in response to severe challenges that threaten breathing stability. Although respiratory dysfunction is the most common medical complication following a traumatic brain injury (TBI), including sleep apnea, little information is available concerning how TBI undermines breathing stability. One possibility is that TBI impairs key forms of compensatory respiratory plasticity that normally stabilize breathing during sleep. One well-studied model of respiratory motor plasticity is long-term facilitation (LTF) elicited by brief exposure to moderate acute intermittent hypoxia (mAIH; 15, 1 min episodes; PaO2=40-50 mmHg). While most often studied (and best understood) in phrenic motor neurons (phrenic LTF), similar plasticity is observed in upper airway motor neurons that innervate muscles contributing to upper airway patency during sleep, such as hypoglossal (XII) motor neurons. Thus, we hypothesized that a single mild TBI induced by closed-head impact model of engineered rotational acceleration (CHIMERA) blunts mAIH-induced phrenic and XII LTF in young (3-4 months) male Sprague Dawley rats 24 hours post-injury. In control rats, mAIH induced phrenic (131±18%; n=4) and XII (142±27%; n=4) LTF. In striking contrast, mAIH induced LTF was nearly abolished 24 hours post-TBI in both phrenic (7±12%; n=4; p< 0.001) and XII (10±22%; n=4; p< 0.001) motor pools. We conclude that mild TBI undermines phrenic and XII LTF through (currently) unknown mechanisms. These findings begin to lay the foundation for insights concerning 1) the impact of mild TBI on any form of respiratory motor plasticity; and 2) XII LTF in any model of acquired neural injury This work was supported by NIH K99HL175029. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.