EFFECTS OF MODERATE HYPERGLYCEMIA ON THE TEMPORAL PROFILE OF BRAIN-TISSUE INTRACELLULAR PH AND [MG2+] AFTER GLOBAL CEREBRAL-ISCHEMIA IN RATS

In an attempt to understand the mechanisms by which preischemic plasma glucose (pg) worsens neurologic and neuropathologic outcomes, we investigated the effect of moderate preischemic hyperglycemia (200 mg/dl < mean plasma glucose < 360 mg/dl) on postischemic energy metabolism, tissue intracellular pH (pHi) and tissue free intracellular pMg(= -log[Mg2+]) over a one week period after transient global cerebral ischemia in the rat. In vivo P-31 nuclear magnetic resonance spectroscopy was performed prior to and daily up to 1 week (wk) in rats after 12 min of forebrain ischemia, induced by bicarotid occlusion concurrent with systemic hypotension. Preischemic plasma glucose significantly affected 1 wk postischemic survival (p = 0.05, Fisher's exact test). The temporal profile of the brain tissue pHi was significantly different (p < 0.03) between the moderate hyperglycemic (H-1wk, n = 7, mean pg = 266.0 +/- 47.3 mg/dl) and the normoglycemic (N-1wk, n = 8, mean pg = 91.2 +/- 23.7 mg/dl) ischemic animals over 1 wk. Postischemic tissue alkarosis was measured at 24 (p = < 0.006) and 48h (p = 0.001) postischemia in the N-1wk group. A single marginally significant (p = 0.011) mean pHi upshift was measured at 72h postischemia in the H-1wk group. The mean change in pHi at 24h postischemia from the baseline values in moderate hyperglycemic animals that survived only 48h after ischemia (H-48h, n = 6, mean pg = 298.8 +/- 70.1 mg/dl) was significantly lower (p = 0.02) than that of the N-1wk ischemic animals. No differences were detected in the relative area ratios of phosphate metabolites and [Mg2+] profiles between the N-1wk and H-1wk groups. Scattered dark neurons were present in the cortices of the H-1wk ischemic animals. The present study demonstrates that a mild glucose load, administered 40 min before forebrain ischemia, is detrimental to long term survival and indicates that the pHi regulatory mechanism is sensitive to and has a long term response to a moderate preischemic glucose load, independent of the recovery of cerebral phosphate metabolism and free intracellular [Mg2+].