The effect of rapid preconditioning on the microglial, astrocytic and neuronal consequences of global cerebral ischemia

Previous studies indicated preconditioning of the brain with sublethal isch emic insults separated by many hours, protected tissues from a subsequent l ethal insult. We recently reported neuroprotection by a rapid preconditioni ng paradigm where a sublethal ischemic insult preceded test ischemia by onl y 30 min. We hypothesize that neuroprotection caused by the rapid ischemic preconditioning (TPC) will result in lowered microglial, reactive astrocyte s and increased normal neuronal cell counts. Wistar rats underwent normothe rmic (36.5-37 degrees C) global cerebral ischemia, produced by bilateral ca rotid artery ligation after lowering mean systemic blood pressure. The prec onditioning ischemic insult lasted 2 min and was associated with a sufficie nt, amount of time to provoke anoxic depolarization. After a 30-min reperfu sion period, 10-min test ischemia was produced, and histopathology was asse ssed 3 and 7 days later. Normal neuronal cell counts for control rats at 3 days survival were significantly lower (by 58%) than in IPC animals. Althou gh there was a trend toward protection in IPC rats at 7 days, the differenc e in normal neuronal cell count between the IPC and control groups was not significant. IPC rats at 3 days but not 7 days of survival showed a signifi cantly lower microglial cell count (by 56%) than control rats. These result s showed that the protection induced through LPC at 3 days of survival prod uced lower numbers of microglia, while maintaining normal neuronal cells. N o significant differences between control and IPC groups were found in astr ocytic cell count at any time of reperfusion in any region of the hippocamp us studied. The beneficial effects of IPC may, therefore, involve anti-infl ammatory processes that target microglial activation after cerebral ischemi a.