Derangements of Neuronal Activity Following Forebrain Ischemia in Rats : Modification with Graded Hypothermia and Burst suppression dose of Thiopental

Treatment manipulations known to modulate metabolic rate and suppress neuronal activity such as hypothermia or barbiturates are known to provide significant protection after transient episodes of cerebral ischemia. However, detailed mechanism and the differential effects of such a protective effect is not fully understood, The present study was designed to investigate the effects of graded hypothermia and thiopental treatment on local cerebral glucose utilization (LCGU) and synaptic transmission during the period of early reperfusion following transient forebrain ischemia in rats. Forebrain ischemia was induced by bilateral occlusion of carotid arteries for 1 5 min in combination with hemorrhagic hypotension (50mmHg) and followed by 2 hr-reperfusion. Rats were assigned into four basic groups as follows: i) normothermia (37℃) , ii) mild hypothermia (33℃) , iii) moderate hypothermia (27℃) , and iv) thiopental (30mg/kg i.v. followed by 2mg/kg/min: EEG burst suppression dose). In control animals identical treatment protocol was followed, however, ischemia was not induced. After 2 hrs of reperfusion all animals were sacrificed and brains harvested. Transverse coronal sections (20 μm thick) were then prepared and processed for LCGU, 3^H-QNB (mACh receptor) and 3^H-PDBu (PKC) bindings and subsequently evaluated by using autoradiographic techniques. In control animals LCGU decreased with hypothermia by approximately 7-8％ per each℃ in all brain structures analyzed. After thiopental treatment, the decrease in LCGU was not consistent with no decrease measured in hippocampus CAI region. In ischemic groups ischemia-induced decrease in LCGU was attenuated with the most pronounced effect observed in 27℃ temperature group. After thiopental treatment little or no such attenuation was observed. Ischemia-induced decrease in mACh receptor binding and increase in PKC activity in vulnerable brain regions were suppressed by graded hypothermia. No similar effect after thiopental treatment was observed. These data suggest that the difference in neuroprotective effects between hypothermia and burst suppression dose of barbiturate treatment may be related in part to their different efficacy in the suppression of brain metabolism as well as synaptic transmission.

脳虚血

局所脳ブドウ糖代謝

ムスカリン性アセチルコリン受容体

PKC

脳保護