Stroke is one of the most common causes of morbidity and a leading cause of mortality in western society (Bonita, 1992; Wang et al. 2003). Despite some degree of spontaneous functional recovery, 50% of stroke patients are left with a residual motor deficit (Duncan et al., 1992). In addition to the cerebral cortex and basal ganglia, first-time clinical strokes often affect the underlying white matter, resulting in significant long-term cognitive and motor impairments. It has been estimated that more than half of the elderly population have some degree of cerebral white matter lesions (Schmidt et al., 2003; van Dijk et al., 2002). Animal models of stroke have proven to be beneficial in the understanding of the acute pathophysiology of stroke, the neural mechanisms of motor recovery after stroke and in the development of rehabilitation strategies for stroke patients. However, currently there are no studies using animal models of white matter infarct. An animal model of white matter infarct will be valuable in the understanding of the underlying mechanisms of subcortical ischemic stroke, neuronal reorganization leading to motor recovery and most importantly, the evaluation of therapeutic interventions. The goal of this project is to develop such an animal model. Focal injections of the potent vasoconstrictor endothelin-1 will be used to develop a model for future evaluation of potential therapeutic treatments for disabilities resulting from focal infarcts in posterior limb of the internal capsule; a common site for clinical strokes in the cerebral white matter. This dense fiber bundle contains corticofugal axons originating in the motor cortex (including the corticospinal tract), as well as ascending fibers conveying cutaneous and proprioceptive information to the somatosensory cortex. In clinical stroke, injury to the posterior limb of the internal capsule results in substantial sensorimotor deficits. This animal model of white matter infarct will be extremely valuable in future development of therapeutic interventions in stroke treatment of white matter stroke. This will be an important, and unique, animal model for research into pharmaceutical and physical therapeutic effects on recovery of function following white matter infarct and subcortical stroke. ? ? ?
