Summary:The effects of hyperglycemia on the time course of changes in cerebral energy metabolite concen trations and intracellular pH were measured by nuclear magnetic resonance (NMR) spectroscopy in rats sub jected to temporary complete brain ischemia. Interleaved 31p and IH NMR spectra were obtained every 5 min be fore, during, and for 2 h after a 30-min bilateral carotid occlusion preceded by permanent occlusion of the basilar artery. The findings were compared with free fatty acid and excitatory amino acid levels as well as with cations and water content in funnel-frozen brain specimens. One hour before occlusion, nine rats received 50% glucose (12 mJJkg i.p.) and five received 7% saline (12 mllkg i.p.). Before ischemia, there were no differences in cerebral metabolite levels or pH between hyperglycemic rats and controls. During the carotid occlusion, the lactatelN acetylaspartate (Lac/NAA) peak ratio was higher (0.73- 456phate were totally depleted in both groups. Within 5-15 min after the onset of reperfusion, the LaclNAA peak ratio increased further in all rats; however, only in ex tremely hyperglycemic rats (serum glucose> 960 mg/dl) did the lactic acidosis progress rather than recover later during reperfusion. Total free fatty acid and excitatory amino acid levels, but not cation concentration or water content, in brain correlated with serum glucose levels during and after ischemia and with NMR findings after 2 h of reperfusion. Although profound hyperglycemia (se rum glucose of 970-1 ,650 mg/dl) appears to be associated with progression of anaerobic glycolysis and failure of cerebral energy metabolism to recover after temporary complete brain ischemia and with postischemic excito toxic and lipolytic reactions thought to participate in de layed cellular injury, severe hyperglycemia (490-720 mg/ dl) was associated with recovery of energy metabolism.

Summary:The effects of dichloroacetate (DCA) on brain lactate, intracellular pH (pHJ, phosphocreatine (PCr), and ATP during 60 min of complete cerebral ischemia and 2 h of reperfusion were investigated in rats by in vivo IH and 31p magnetic resonance spectroscopy; brain lactate, water content, cations, and amino acids were measured in vitro after reperfusion. DCA, 100 mg/kg, or saline was infused before or immediately after the ischemic period. Preischemic treatment with DCA did not affect brain lac tate or pHi during ischemia, but reduced lactate and in creased pHi after 30 min of reperfusion (p < 0.05 vs. controls) and facilitated the recovery of PCr and ATP during reperfusion. Postischemic DCA treatment also re duced brain lactate and increased pHj during reperfusion Treatments that lower brain lactate levels during ischemia or reperfusion could prevent or reduce subsequent brain injury (Hossmann and Kleihues, 1973;Rehncrona et al., 1981; Siesjo, 1988). Dichlo roacetate (DCA) has been shown to decrease lac tate levels in many tissues (Stacpoole, 1989)

To study the therapeutic effect of phenytoin on cerebral ischaemia and confirm whether or not the effectiveness of phenytoin could be enhanced by combined administration with free radical scavengers, twenty-five dogs were subjected to ischaemia, using the "canine model of the completely ischaemic brain regulated with a perfusion method". Five animals served as untreated controls, fifteen received treatment with several doses of phenytoin and five were treated with 10 mg/kg phenytoin, 2 g/kg mannitol and 30 mg/kg vitamin E. These drugs were administered prior to the production of ischaemia. After one hour ischaemia, cerebral blood flow was restored and the recovery of electrical activity of the brain and the degree of brain swelling were observed for three hours. With regard to the recovery of the EEG, the higher the administered dosage, the better was the degree of recovery of the EEG. And the group which was treated with a combination of phenytoin, mannitol and vitamin E exhibited remarkable recovery of the EEG. With regard to the degree of brain swelling, a similar dose-related suppressive effect was seen in the phenytoin-treated groups. Furthermore, in the combination therapy group, brain swelling was attenuated significantly. Based on these results, it is concluded that phenytoin has a protective effect in cerebral ischaemia and it shows its most remarkable effect when given together with radical scavengers, such as mannitol and vitamin E.