Extracellular pH Changes during Spreading Depression and Cerebral Ischemia: Mechanisms of Brain pH Regulation

We have examined the extracellular pH (pH e ) during spreading depression and complete cerebral ischemia in rat parietal cortex utilizing double-barrelled H + liquid ion exchanger microelectrodes. The baseline pH e of the parietal cortex was 7.33 at a mean arterial Pco 2 of 38 mm Hg. Following spreading depression and cerebral ischemia, highly reproducible triphasic changes in pH e occurred, which were intimately related to the negative deflection in tissue potential (V e ). The changes in pH e for spreading depression (n = 23) were a small initial acidic shift, beginning before the rapid change in V e , followed by a rapid transient alkaline shift of 0.16 pH units, the onset of which coincided with the negative deflection in V e . A prolonged acidic shift of 0.42 pH units then occurred. The maximal decrease in pH e was to 6.97 and the mean duration of the triphasic pH e change was 7.8 min. The lactate concentration in brain cortex increased from baseline 1.2 m M to 7.0 m M (n = 6) during the maximal acidic change in spreading depression. In addition, lactate levels correlated well with resolution of the pH e changes during spreading depression. The triphasic pH e changes following complete cerebral ischemia were an initial acidic shift of 0.43 pH units which developed over 2 min, then an alkaline shift of 0.10 pH units coincident with the negative deflection in V e , and a final acidic shift of 0.26 pH units. The terminal pH e was 6.75. Superfusion of the cortex with inhibitors of carbonic anhydrase (acetazolamide), Na + /H + counter transport (amiloride), and Cl − /HCO 3 − countertransport (4,4'-diisothiocyanostilbene-2,2'-disulfonic acid) altered the triphasic pH e changes in a similar fashion for both spreading depression and cerebral ischemia, providing insights into the pH e regulatory mechanisms in mammalian brain.