Alterations of calcium/calmodulin-dependent protein kinase II activity in ischaemia-induced neuronal death and neuronal protection against ischaemia in the gerbil hippocampus

To clarify the relation between neuronal protection against ischaemia and c alcium/calmodulin-dependent protein kinase II (CaM kinase II) activity, we investigated temporal alterations of the kinase activity in the hippocampus after transient forebrain ischaemia under neuroprotective conditions, empl oying the gerbil bilateral carotid artery occlusion model. The hippocampal CA1 neuronal density at 2 hours after 5 minutes of forebrai n ischaemia was 214.7 +/- 25.8 /mm (mean +/- S.D.), and did not differ from the control significantly; however, it decreased to 11.7 +/- 4.2 /mm at 7 days after the ischaemia. The neuronal density at 7 days after the ischaemi a was 185.1 +/- 18.5 under the hypothermic conditions, 128.7 +/- 19.6 with the brief ischaemic pretreatment, 65.0 +/- 13.4 with administration of MK-8 01, and 20.5 +/- 4.2 with the repetitive hyperthermic pretreatment, respect ively. These results indicated that the preservation of the Ca2+/calmodulin-depend ent activity of cytosolic CaM kinase II after ischaemia parallelled the neu roprotective effect in the gerbil hippocampus. Thus, it is suggested that t he preservation of the activity may be involved in the mechanism of neurona l protection against ischaemia.