Enhancement of Hippocampal Neurogenesis following Small Ischemic Cortical Infarcts in the Adult Brain

Stimulation of cell proliferation and neurogenesis in the adult dentate gyrus (DG) has been observed after focal and global brain ischemia. There is some evidence that this proliferative response is at least in part mediated by NMDA-dependent mechanisms. We here analyzed the effects of cortical infarcts on cell proliferation and differentiation after small cortical infarcts leaving the hippocampal formation intact. Using the photothrombosis model, focal ischemic infarcts were induced in different cortical areas (sensorimotor forelimb and hindlimb cortex) and proliferating cells were labeled at day 3–14 after infarct induction with bromodeoxyuridine (BrdU, 50mg/kg, i.p.). 4 and 10 weeks following ischemia, immunocytochemistry was performed with markers. When compared with β antibodies against neuronal (NeuN) and glial (S100 sham-operated controls) both animals with infarcts in the forelimb as well as hindlimb cortex revealed an increase in BrdU-positive cells at 4 weeks after the insult. The ipsilateral DG usually showed more BrdU-positive cells compared with the contralateral side although there was no significant difference. At 10 weeks after ischemia the BrdU-positive cell number was still increased in both groups reaching significance in animals with infarcts in the hindlimb cortex. Confocal laser scanning microscopy revealed an increase in neurogenesis in all groups that was more pronounced 10 weeks after the infarct. Notably, this proliferative response was not influenced by administration of the NMDA receptor antagonist MK-801 during lesion induction. The present study demonstrates that even small cortical infarcts induce an increase in cell proliferation and neurogenesis in the DG. It further indicates that these effects are not mediated by early NMDA-dependent excitatory mechanisms occurring during lesion induction. Supported by DFG Re 1315/3–1.