Hypothermia enhances the colocalization of calmodulin kinase IIα with neuronal nitric oxide synthase in the hippocampus following cerebral ischemia.
Hypothermia has been shown to have neuroprotective effects against neurotrauma and cerebrovascular disease. Cerebral ischemia induces the activation of calcium/calmodulin kinase II (CaM-KII), which modulates many enzymes. We have previously demonstrated that CaM-KIIα downregulates neuronal nitric oxide synthase (nNOS) activity. However, precise details regarding the neuroprotective mechanism of hypothermia largely remain to be elucidated. Therefore, in this study, we investigated the neuroprotective mechanism of hypothermia, focusing on the association between CaM-KIIα and nNOS in CA1 hippocampus after focal cerebral ischemia in mice. The temperature was maintained at normothermia (36.5-37.5°C) or mild hypothermia (31.5-32.5°C) during these procedures. Focal cerebral ischemia induced significant dissociation of CaM-KIIα from nNOS in the CA1 hippocampus but not in the cerebral cortex under normothermia. Hypothermia did not change the expression of nNOS, but it significantly induced the colocalization of CaM-KIIα with nNOS in CA1 hippocampus immediately after cerebral ischemia. These results presumably result in the attenuation of nNOS activity and could contribute to the tolerance to post-ischemic damage. This effect could be one of the neuroprotective mechanisms of hypothermia.
Department of Neurosurgery, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi 466-8550, Japan.
Shigemasa
S
Hayashi
Koji
K
Osuka
Yasuo
Y
Watanabe
Muneyoshi
M
Yasuda
Masakazu
M
Takayasu
Toshihiko
T
Wakabayashi
D000818:Animals; D002545:Brain Ischemia / Q000473:pathology* / Q000628:therapy*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D007839:Functional Laterality; D006624:Hippocampus / Q000378:metabolism*; D007036:Hypothermia, Induced / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D013997:Time Factors
D052248:Nitric Oxide Synthase Type I; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2