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)
