New insights regarding the cellular biology associated with neurotrauma and neurodegenerative disease have led to several proposed therapeutic interventions directed at functional recovery after spinal cord injury (SCI). It is now more conceivable than before that some useful improvements could be obtained through a convergence of cellular, pharmacological, molecular and/or rehabilitative treatment modalities. However, before any innovative strategies can be judiciously advanced to the clinical setting, there ideally needs to be rigorous analysis of functional impact at both the behavioral and cellular levels in animal models of SCI that approximate the human condition from neuropathological and pathophysiological perspectives. Various features of SCI also should be considered since the efficacy of a potential treatment might vary according to different lesion conditions such as: the spinal level of injury, the type of trauma sustained, the distance of the lesion from neuronal pools in which functional improvement would be most desired, the type of recovery being sought, and the time after injury that a particular therapeutic protocol is instituted. It also would be of benefit to be able to anticipate how a treatment approach could interface with intrinsic repair processes (i.e., neuroplasticity). The three component subprojects of this Program, along with the two laboratory Cores described, will address these issues by exploring the effects of fetal neural tissue transplants in relation to loss of interlimb coordination, occurrence of spasticity, and deficits in respiratory- associated phrenic motoneuron activity after midthoracic, upper lumbar, and cervical spinal cord injuries, respectively. These studies will particularly emphasize spontaneous and graft-mediated functional changes in relation to clinically-relevant contusion/compression injuries and will entail a fusion of qualitative and quantitative neuroanatomical, neurophysiological, magnetic resonance imaging, and behavioral methods. The emphasis on fetal cell transplantation reflects an operational bias of this proposal -namely, that some form of cellular grafting strategy will ultimately constitute part of the overall therapeutic formula directed at functional improvement. At the preclinical level, fetal tissue grafting continues to provide a legitimate and compelling experimental tool whereby a better understanding can be obtained concerning the potential for engineering behavioral recovery after SCI. The coordination of these investigations via the Program Project construct also will provide a valuable template upon which to base future analyses of other viable therapeutic interventions complementary to cellular transplantation.
Showing the most recent 10 out of 27 publications
