Is cell death necessary for hippocampal mossy fiber sprouting?

To examine the relationship between cell death and sprouting of the mossy fibers, repeated seizures of the hippocampal-parahippocampal circuit were elicited in anesthetized rats. The presence of mossy fiber growth was assessed with the Timm's stain for zinc. At 4 weeks, after 18 repeated seizures, there was a significant increase in the degree of zinc containing granules in the inner molecular layer of the dentate gyrus. The amount of sprouting was less than that seen four weeks after a single injection of kainic acid. A silver impregnation stain and an assay for damaged DNA were used to detect damaged or dying neurons and immunohistochemistry for a 72 kDa heat shock protein was used to detect any neurons that had suffered potentially injurious stress. The same number of repeated seizures that caused sprouting of the mossy fibers did not cause detectable cell death or severe stress in any cells within the hippocampus, subicular region or adjacent entorhinal cortex. These experiments demonstrate that repeated seizures of the hippocampal-parahippocampal circuits can cause sprouting of mossy fibers in the absence of evidence of cell death. This supports the hypothesis that alterations in intrinsic neural excitability and impulse activity from the dentate gyrus can result in growth of axonal processes in the adult rat brain.