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 calcium/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, employing the gerbil bilateral carotid artery occlusion model. The hippocampal CA1 neuronal density at 2 hours after 5 minutes of forebrain 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 ischaemia 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-801, and 20.5 +/- 4.2 with the repetitive hyperthermic pretreatment, respectively. The Ca2+/calmodulin-dependent activity of CaM kinase II in the hippocampal cytosolic fraction was decreased to 47.5% of the control value at 2 hours after the ischaemia, when CA1 neuronal death was not observed. In contrast, the activity was 98.8% of the control under the hypothermic conditions, 91.4% with the brief ischaemic pretreatment, 71.2% with administration of MK-801, and 47.9% with the repetitive hyperthermic pretreatment, respectively. These results indicated that the preservation of the Ca2+/calmodulin-dependent activity of cytosolic CaM kinase II after ischaemia parallelled the neuroprotective effect in the gerbil hippocampus. Thus, it is suggested that the preservation of the activity may be involved in the mechanism of neuronal protection against ischaemia.
Uno
H
H
Department of Neurosurgery, Fukui Medical University, Japan.
Kobayashi
H
H
Handa
Y
Y
Kabuto
M
M
Kubota
T
T
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002452:Cell Count; D002470:Cell Survival; D004195:Disease Models, Animal; D005260:Female; D005849:Gerbillinae; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006979:Hyperthermia, Induced; D007036:Hypothermia, Induced; D009410:Nerve Degeneration; D018696:Neuroprotective Agents / Q000494:pharmacology; D012008:Recurrence; D013997:Time Factors
D018696:Neuroprotective Agents; D017871:Calcium-Calmodulin-Dependent Protein Kinases