Neurogenesis in the adult dentate gyrus after cortical infarcts: effects of NMDA receptor blockade and anti-inflammatory treatment

Stimulation of cell proliferation and neurogenesis in the adult dentate gyrus (DG) has been observed after focal and global brain ischemia but only little is known about the underlying mechanisms. We analyzed neurogenesis after small cortical infarcts leaving the hippocampal formation and subcortical regions 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). At 2, 4, and 10 weeks after ischemia, immunocytochemistry was performed with immature neuronal (DCX), mature neuronal (NeuN) and glial (S100beta) markers. When compared with sham-operated controls, animals with infarcts in the forelimb as well as hindlimb cortex revealed an increase in survival of new-born progenitor cells at 4 and 10 weeks after the insult with predominance at the ipsilateral side. Triple immunofluorescence and confocal laser scanning microscopy revealed an increase in neurogenesis in all groups that was more pronounced 10 weeks after the infarct. Application of the NMDA-receptor antagonist MK-801 during lesion induction significantly enhanced neurogenesis in the dentate gyrus. An even stronger increase in newborn neurons was observed after anti-inflammatory treatment with indomethacine during the first 16 days of the experiment. The present study demonstrates that small cortical infarcts also increase neurogenesis in the DG and that these processes can be stimulated by NMDA receptor blockade and anti-inflammatory treatment. (Supported by DFG Re 1315/3–1, IZKF TP 1.7)