Effect of Mild Hypothermia on Cytoskeletal Damage Related to Intracellular Signal Transduction System after Progressive Cerebral Ischemia

It has been demonstrated that intracellular increases in calcium induced by massive release of excitatory amino acid and by increased phospholipid metabolism during and after ischemia play an important role in brain damage. Furthermore, recent studies revealed that mild hypothermia (2-5℃ reduction of brain temperature below normothermia) provided protective effect, though the mechanism of this effect is obscure. The present study was designed to gain further insight into the mechanism for neuroprotective effect of mild hypothermia especially focussing on the changes of intracellular signal transduction system in a model of progressive forebrain ischemia intherat. Two series of study were performed in 79 male Wistar rats in which the brain temperature was kept either at normothermia (37℃ ) or at a mild hypothermia (33℃ ) during the ischemic period. Forebrain ischemia (10, 20, and 30 min duration) was produced by bilateral occulusion of the carotid artery combined with hemorrhagic hypotension (mean BP= 50mmHg). In the first series of experiment, neuropathological damages were assessed by H&E stain for neuronal damage and by the immunohistochemical reactivity for microtubule-associated protein (MAP2) in the cerebral cortex, caudate nucleus, hippocampus CA1 and thalamus. In the second series, the changes in binding for 3^H-PDBu, 3^H-forskolin, and 3^H-PN200-110 were measured to evaluate the functional changes of protein kinase C, adenylate cyclase, and L-type Ca ion channel, respectively. In additional rats, local cerebral blood flow (LCBF) during the ischemic period was measured using ^<14>C-iodo antipyrine autoradiography. LCBF was progressively decreased in all structures examined. After 10 min of ischemia, LCBFs were 7%, 10%, 10%, and 24% in the cerebral cortex, caudate nucleus, hippocampus CA1 and thalamus

脳虚血

脳低温

MAP2

Cキナーゼ

アデニル酸シクラーゼ