Post-stroke neurogenesis is an endogenous restorative mechanism that shows promise for contributing to functional recovery. Investigations of cell proliferation being driven and effectively maintained in reorganizing brain regions can be applied to the development of more effective therapy strategies after ischemic stroke. Our main question is to investigate if rehabilitative training after ischemic damage, which improves behavioral function, can also increase cell proliferation and encourage the differentiation and maintenance of newly formed neurons. We will approach this question by first establishing the level of cell proliferation and neurogenesis in an animal (adult rat) model of focal cortical ischemia with and without rehabilitative therapy. Next, we will investigate which component of neurogenesis, proliferation or maintenance, is affected by rehabilitative training by using pulse labeling of new cells followed by short or long term rehabilitation training periods. Lastly, we will explore delayed rehabilitative training effects on stroke-induced cell proliferation. For all proposed studies, we will utilize a rehabilitation task (skilled reaching) which has repeatedly been found to enhance behavioral performance after ischemic lesions of the sensorimotor cortex. In an effort to (1) target forelimb deficits induced by the lesions and (2) engage remaining cortex in potential plastic events, rehabilitation will be focused on the impaired forelimb. In addition, we will investigate the level of cell proliferation by measuring and phenotyping cells labeled with a mitotic marker (bromodeoxyuridin; BrdU) in the peri-lesion area, the striatum (indicated as an area of migrating new cells after injury), and the subventricular zone (SVZ; an area of ongoing proliferation in adults). By accomplishing this proposal, we are confident that the results will be important for further understanding the therapeutic potential of experience-facilitated cell proliferation. ? ? ?
| Allred, Rachel P; Adkins, DeAnna L; Woodlee, Martin T et al. (2008) The vermicelli handling test: a simple quantitative measure of dexterous forepaw function in rats. J Neurosci Methods 170:229-44 |
| Maldonado, Monica A; Allred, Rachel P; Felthauser, Erik L et al. (2008) Motor skill training, but not voluntary exercise, improves skilled reaching after unilateral ischemic lesions of the sensorimotor cortex in rats. Neurorehabil Neural Repair 22:250-61 |
