AJP - Regulatory, Integrative and Comparative Physiology, Vol 260, Issue 3 581-R588, Copyright © 1991 by American Physiological Society

ARTICLES

Dynamics of interstitial and intracellular pH in evolving brain infarct

M. Nedergaard, R. P. Kraig, J. Tanabe and W. A. Pulsinelli
Department of Neurology and Neuroscience, Cornell University Medical College, New York, New York 10021.

We examined the relationships between intracellular pH (pHi) and interstitial pH (pHe) in a rat model of focal ischemia. Interstitial pH was measured with pH-sensitive microelectrodes, and the average tissue pH was measured with the [14C]dimethadione method in rats subjected to occlusion of the right middle cerebral and common carotid arteries (MCA-CCAO). In normal cortex, pHe and pHi were 7.24 +/- 0.97 and 7.01 +/- 0.13 (means +/- SD, n = 6), respectively. In the ischemic cortex, pHe fell to 6.43 +/- 0.13, whereas pHi decreased only to 6.86 +/- 0.11 (n = 5) 1 h after MCA-CCAO. After 4 h of ischemia, the pHe was 6.61 +/- 0.09 and pHi was 6.62 +/- 0.20 (n = 4). Treatment with glucose before ischemia markedly lowered the pHe (5.88 +/- 0.17) but not pHi (6.83 +/- 0.03, n = 4) measured 1 h after ischemia. In the ischemic cortex of animals made hypoglycemic by pretreatment with insulin, neither pHe (7.25 +/- 0.06) nor pHi (6.99 +/- 0.13, n = 4) decreased. The demonstrated difference in pHi and pHe indicates that some cells remained sufficiently functional to maintain a plasma membrane gradient of protons within the evolving infarct. If the calculated pHi values accurately reflect the true pHi of cells within zones of severe focal ischemia, then cerebral infarction can proceed at pHi levels not greatly altered from normal.

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