Rehabilitative therapies differentially alter proliferation and survival of glial cell populations in the perilesional zone of cortical infarcts.

Rehabilitative therapies after stroke are designed to improve remodeling of neuronal circuits and to promote functional recovery. Only very little is known about the underlying cellular mechanisms. In particular, the effects of rehabilitative training on glial cells, which play an important role in the pathophysiology of cerebral ischemia, are only poorly understood. Here, we examined the effects of rehabilitative therapies on proliferation and survival of distinct glial populations in the perilesional area of photochemically induced focal ischemic infarcts in the forelimb sensorimotor cortex in rats. Immediately after the infarct, one group of animals housed in standard cages received daily sessions of skilled reaching training of the impaired forelimb; a second group was transferred to an enriched environment, whereas a third control group remained in standard cages without further treatment. Functional recovery was assessed in a sensorimotor walking task. To label proliferating cells, bromodeoxyuridine (BrdU) was administered from day 2 until day 6 postinfarct. Proliferation and survival of astrocytes, microglia/macrophages, and immature and mature oligodendrocytes in the perilesional zone were immunocytochemically quantified at day 10 and 42. Using this approach, we demonstrate that enriched environment and reaching training both significantly improve functional recovery of the impaired forelimb. Furthermore, these therapies strongly reduce the proliferation of microglia/macrophages in the perilesional zone, and daily training of the impaired forelimb significantly increased the survival of newly generated astrocytes. Our data, therefore, demonstrate that rehabilitative therapies after cortical infarcts not only improve the functional recovery but also significantly influence the glial response in the perilesional zone.