Effects of sensorimotor activity on the perilesional glial response after cortical infarcts

Focal cerebral ischemia in the adult central nervous system evokes a strong glial proliferative response forming a dense astroglial scar in the perilesional area. Increasing evidence indicates that the role of this proliferation of astrocytes but also oligodendrocytes and microglial cells is ambiguous comprising protective and deleterious effects as well. Here, we analyzed the effects of activity on the perilesional glial response after circumscribed cortical infarcts in the forelimb sensorimotor cortex using a photochemical model in rats. Sham-operated animals served as controls. Following infarct induction one experimental subgroup was transferred to an enriched environment, a second group received daily reaching training of the impaired forelimb (reaching of 100 food pellets per day), whereas a third group remained in the standard cage. In order to analyze the proliferative response bromodeoxyuridine (BrdU) was applied at day 2 to 6 after beginning of the experiments. Animals were perfused at day 10 to assess ongoing proliferation and at day 42 to analyze the survival of the BrdU-labeled cells in the perilesional area. At day 10 the proliferative response was significantly increased in the standard group compared to the reaching training and enriched environment group. However, at day 42 the reaching training showed the significantly highest numbers of surviving BrdU positive cells. Immunocytochemical co-localization studies and confocal laser scanning microscopy revealed that nearly all BrdU-labeled cells displayed glial phenotypes. Furthermore, we provide evidence that astrocytes, oligodendrocytes and microglial cells were differentially influenced by the activity. Our data clearly demonstrate that the perilesional glial response can be significantly influenced by environmental enrichment and specific sensorimotor training. (Supported by DFG Re 1315/3–1 and IZKF TP 1.7)