Electrical stimulation of cerebellar fastigial nucleus protects rat brain,in vitro, from staurosporine-induced apoptosis

Electrical stimulation of the cerebellar fastigial nucleus (FN) elicits a p rolonged (similar to 10 days) and substantial (50-80%) protection against i schemic and excitotoxic injuries. The mechanism(s) of protection are unknow n. We investigated whether FN stimulation directly protects brain cells aga inst apoptotic cell death in an in vitro rat brain slice culture model. Rat s were electrically stimulated in FN or, as control, the cerebellar dentate nucleus (DN). Coronal slices through the forebrain were explanted, exposed to staurosporine, harvested, and analyzed for caspase-3 activity by a fluo rescence assay. FN, but not DN, stimulation significantly reduced staurospo rine-induced caspase-3 activity by 39 +/- 7% at 3 h, 31 +/- 3% at 6 h and 2 6 +/- 40% at 10 h of incubation. Immunocytochemistry revealed FN-specific r eductions in activated caspase-3 mainly in glial-like cells throughout the forebrain. FN stimulation also results in a 56.5% reduction in cytochrome c release upon staurosporine incubation. We conclude that neuroprotection el icited from FN stimulation can directly modify the sensitivity of brain cel ls to apoptotic stimuli and thereby suppress staurosporine induced apoptosi s in adult rat brain slices. This model indicates that neuroprotection can be studied in vitro and provides new insight into the potential role of gli al cells in ischemic protection of neurons induced by FN stimulation.