Degeneration of newly formed CA1 neurons following global ischemia in the rat.

The pyramidal neurons of the hippocampal CA1 region are essential for spatial learning and memory and are almost entirely destroyed 7-14 days after transient cerebral ischemia (DAI). Recently, we found that CA1 neurons reappeared at 21-90 DAI, in association with a recovery of ischemia-induced deficits in spatial learning and memory. However, at 125 DAI the number of neurons was fewer than at 90 DAI, suggesting that the new nerve cells undergo neurodegeneration during this time period. We therefore investigated whether neuronal degeneration occurred between 90 and 250 DAI and how this related to learning and memory performance. We found that many of the new CA1 neurons previously seen at 90 DAI had disappeared at 250 DAI. In parallel, large mineralized calcium deposits appeared in the hippocampus and thalamus, in association with neuroinflammatory and astroglial reactions. In spite of the extensive CA1 damage, the ischemic rats showed no deficiencies in spatial learning and memory, as analyzed in the Morris water maze and a complimentary water maze test based on sequential left-right choices. However, ischemia rats showed a general increase in swim length in the Morris water maze suggesting altered search behaviour. Taken together, these results indicate that the CA1 neurons that reappear after transient global ischemia to a large extent degenerate at 125-250 DAI, in parallel with the appearance of a less efficient search strategy.