Abstract
To examine the involvement of manganese superoxide dismutase (MnSOD) in the acquisition of ischemic tolerance by CAI neurons, we performed in situ hybridization histochemistry and immunocyto-chemistry for MnSOD in gerbil hippocampus following lethal or non-lethal transient cerebral ischemia to the hippocampal CA1 neurons. We produced transient global cerebral ischemia by occluding the common carotid artery bilaterally. The animals were divided into three groups : 1) a single 5-min ischemic insult group, 2) a single 2-min ischemic insult group, and 3) a repeated ischemic insult group with underwent a 5-min period of ischemia 2 days after a single 2-min period of ischemia. Histochemical examination revealed a transient increase in the expression of MnSOD mRNA without expression of MnSOD protein in CA1 pyramidal neurons following 5 min of ischemia. However, at 3 days of ischemia, MnSOD mRNA as well as its protein was expressed in the glial cells such as microglia which proliferated in the white matter region of CAl. On the contrary, both MnSOD mRNA and protein were expressed in the CAl pyramidal neurons by 1 day after non-lethal 2 min of ischemia. This expression was lasting during 7-day recirculation following the ischemia. Little MnSOD expression was noted in the reactive microglia. Repeated ischemia demonstrated a subtle change in MnSOD protein expression as compared to that expressed before the Last ischemic insult. Lethal ischemia causing delayed neuronal death in the CAl is associated with the loss of MnSOD, while non-lethal ischemia inducing ischemic tolerance by the CAl neurons is associated with the increase of MnSOD. These results suggested that MnSOD in the neurons has an important role in the cell defense mechanism against oxidative stress.
