Ischemic preconditioning attenuates of ischemia-induced degradation of spectrin and tau: implications for ischemic tolerance.

Global ischemia selectively induces CA1 neuronal death in the hippocampus. Pretreatment with non-lethal ischemia (i.e. ischemic preconditioning) prevents CA1 neuronal death induced by lethal ischemia. While ischemic tolerance is a well-known phenomenon, the underlying molecular mechanisms are not fully understood. Cytoskeletal proteins including α-spectrin, tau, and microtubule-associated protein 2 (MAP-2) are indispensable for the maintenance of neuronal homeostasis. Here, we report the effects of ischemic preconditioning on the ischemia-induced degradation of cytoskeletal proteins α-spectrin, tau, and MAP-2 in the rat CA1 region. We found that most neurons of the CA1 region had died after 5 min of ischemia. However, exposing the brain to 3 min of ischemic preconditioning 3 days earlier significantly reduced the number of neuronal death. A significant degradation of α-spectrin and tau, but not of MAP-2, was found in the CA1 region after 5 min of ischemia. Ischemic preconditioning attenuated the ischemia-induced massive degradation of α-spectrin and tau. Our results suggest that the attenuation of ischemia-induced degradation of α-spectrin and tau by ischemic preconditioning may be associated with the neuroprotective mechanism of the ischemic tolerance.