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

Abstract

Summary:We have examined the extracellular pH (pH e) during spreading depression and complete cerebral isch emia in rat parietal cortex utilizing double-barrelled H + liquid ion exchanger microelectrodes. The baseline pHe of the parietal cortex was 7.33 at a mean arterial Peoz of 38 mm Hg. Following spreading depression and cerebral ischemia, highly reproducible triphasic changes in pHe occurred, which were intimately related to the negative deflection in tissue potential (Ye). The changes in pHe for spreading depression (n = 23) were a small initial acidic shift, beginning before the rapid change in Ye, followed by a rapid transient alkaline shift of 0.16 pH units, the onset of which coincided with the negative deflection in Ye• A prolonged acidic shift of 0.42 pH units then oc curred. The maximal decrease in pHe was to 6.97 and the mean duration of the triphasic pHe change was 7.8 min. The lactate concentration in brain cortex increased fromThe adaptive response by the brain microenvi ronment to altered extracellular pH (pHe) remains poorly understood, partially due to the difficulty in directly measuring the interstitial hydrogen ion con centration. Now, however, high-fidelity recordings of pH changes in mammalian brain interstitium can be obtained with double-barrelled H+ liquid ion ex changer (LIX) microelectrodes (Ammann et aI., 1981; Kraig et aI., 1983). The use of similar LIX microelectrodes has greatly facilitated study of Dr. Mutch's present address is Department of Anesthesia, St. Boniface General Hospital, 40 9 Ta che Avenue, Winnipeg, Man itoba, Canada R2H 2A6.Address correspondence and reprint requests to Dr. Hansen at Department of Medical Physiology A, University of Copen hagen, The Panum Institute, B1egdamsvej 3, DK-22 00, Copen hagen N, Denmark.Abbreviations used: DIDS, 4,4'-Diisothiocyanostilbene-2,2' disulfonic acid; DNDS, 4, 4' -dinitrostilbene-2,2' -disulfonic acid; EH+, potential derived from H+ activity; LlX, liquid ion ex changer; pHe, extracellular pH; Ve, tissue potential. 17 baseline 1.2 mM to 7.0 mM (n = 6) during the maximal acidic change in spreading depression. In addition, lactate levels correlated well with resolution of the pHe changes during spreading depression. The triphasic pHe 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 Ye, and a final acidic shift of 0.26 pH units. The terminal pHe was 6.75. Superfusion of the cortex with inhibitors of carbonic anhydrase (acetazol amide), Na+/H+ counter transport (amiloride), and Cl-/ HC03' countertransport (4,4' -diisothiocyanostilbene-2,2' disulfonic acid) altered the triphasic pHe changes in a similar fashion for both spreading depression and cerebral ischemia, providing insights into the pHe regulatory mechanisms in mammalian brain.

Extra- and Intracellular pH in the Brain during Seizures and in the Recovery Period following the Arrest of Seizure Activity

“…From the seven experi ments available, the pre epileptic pHe was 7.31 ± 0.02. Since this value is similar to that reported by others (Kraig et aI., 1983;Mutch and Hansen, 1984), we assumed that the pre seizure pHe was 7.31 in each experiment. It was then possible to calculate the HC03 -concentration from the Hendersson Hasselbalch equation.…”

“…The electrodes were constructed as described in two recent communications (Kraig et aI., 1983;Mutch and Hansen, 1984). Following silanization, the tip of the pH barrel was filled with the pH "cocktail" developed by Ammann et al (1981), and the barrel was back-filled with a phosphate buffer (pH 6.5).…”

“…Although liquid ion-exchange pH electrodes with tip diameters of 1-3 /-Lm should provide reli able and non traumatic estimates of pHe (Kraig et aI., 1983;Mutch and Hansen, 1984), some prob lems of interpretation exist. One of these concerns the absolute pH values obtained.…”

Terminal spreading depolarization and electrical silence in death of human cerebral cortex

“…These overlapped with the terminal SD. They seemed to start with the final drop in p ti O 2 , which in addition is characterized by progressive acidification 46, 47. This timing suggests that they resulted, at least partially, from interferences of p ti O 2 and pH with platinum.…”

In vivo Measurement of Regional Brain and Tumor pH Using [14C]Dimethyloxazolidinedione and Quantitative Autoradiography. II: Characterization of the Extracellular Fluid Compartment Using pH-Sensitive Microelectrodes and [14C]Sucrose

“…15 ml/g, white matter water content was 0.69 ml/g, and white matter extracellular water volume was O. II ml/g (Arnold et aI., 1985). Based on pre viously reported microelectrode measurements of normal brain pHe (Cragg et aI., 1977;Davies and Nolan, 1982;Mutch and Hansen, 1984;Kraig et aI. , 1985Kraig et aI.…”