The trainee is a physician with substantial clinical expertise in the care of individuals who have sustained a traumatic spinal cord injury (SCI). With the mentorship of a senior investigator, he will acquire skill sets vital to the performance of laboratory research relevant to SCI. The proposed research development plan will facilitate the development of the trainee into an effective, independent investigator. Recovery of function after SCI requires not only the reestablishment of connections from the brain to the spinal cord, but also the presence of intact and functional lower motor neurons (LMN) and neuromuscular junctions (NMJ). SCI compromises conduction of motor signals through the spinal cord, resulting in a population of LMNs deprived of supraspinal input. Unexpectedly, electrophysiological studies in humans following SCI have suggested the presence of peripheral denervation; despite the fact that LMNs caudal to the lesion escape direct injury. Animal models of SCI have revealed synaptic instability at peripheral NMJs. The PIs, therefore, propose to study factors that affect LMN and NMJ health and function following SCI. More specifically, they will (1) investigate passive exercise as a therapeutic strategy for maintaining hind limb NMJ stability following SCI and (2) explore underlying mechanisms through which exercise impacts NMJ stability. This will be accomplished through the use of immunohistochemical and electrophysiological techniques that will qualitatively and quantitatively document NMJ stability and instability following different exercise paradigms. Gene expression of select neurotrophic factors will be measured in LMNs and innervated muscle using laser micro dissection combined with reverse transcriptase polymerase chain reaction (PCR) & immunoassays. ? ? Human SCI is a devastating event that affects approximately 11,000 individuals annually in the United States, with an accompanying prevalence of 222,000 to 285,000. All therapeutic strategies for human SCI will require the presence of viable LMNs and their accompanying connections to peripheral skeletal muscle. It is therefore of vital importance to understand the nature of physiological alterations to the LMN and NMJ following SCI as well as therapeutic strategies that could impact such changes. ? ? ? ?
| Ollivier-Lanvin, Karen; Lemay, Michel A; Tessler, Alan et al. (2009) Neuromuscular transmission failure and muscle fatigue in ankle muscles of the adult rat after spinal cord injury. J Appl Physiol 107:1190-4 |
