Rehabilitative training effects on cell proliferation after cortical ischemic damage

The main goal of this dissertation was to investigate if rehabilitative training after ischemic damage can increase cell proliferation and encourage the differentiation and maintenance of newly formed neurons. For all studies, I utilized a rehabilitative training task which has repeatedly been found to enhance behavioral performance after ischemic lesions of the sensorimotor cortex. Training was focused on the impaired forelimb in order to (1) target forelimb deficits induced by the lesions and (2) engage remaining cortex in potential plastic events. The level of cell proliferation was investigated by measuring and phenotyping cells labeled with a mitotic marker (bromodeoxyuridine) in the peri-lesion area and various other regions. First, in an animal model of cortical ischemia, the level of cell proliferatoin measured in rehabilitated animals after ischemic damage was significantly decreased in peri-lesion cortex compared to non-rehabilitated animals. In order to investigate which component of cell generation, proliferation or maintenance, was affected by rehabilitative training, pulse labeling of new cells followed by short or long term training periods was accomplished. This study revealed thatrehabilitative training had increased cell proliferation that occurred early after ischemic damage and the maintenance of these early generated cells were significantly increased in the peri-lesion cortex of rehabilitated animals compared to controls. Lastly, in order to verify the results of the first study (experience induced reduction of new cells in periinfarct tissue) pulse labeling of new cells during a mid-time point of rehabilitation period after ishemic lesions was employed and resulted in the same significantly reduced level of new cells in peri-infarct tissue of rehabilitated animals compared to controls. In all studies, the proportion of the neuronal and astrocyte phenotype of newly generated cells was not significantly affected by rehabilitative training after ischemic damage. However, a significant increased accumulation of new microglia was seen in rehabilitated animals, but reactive microglia produced early after ischemic damage were not significantly maintained which indicates a possible dual role that microglia during post-operative rehabilitative training. Together these studies indicate that functionally beneficial behavioral experience can affect cell proliferative responses, and mainitenance of newly generated non-neuronal cells early after ischemic damage.