DYNAMICS OF INTERSTITIAL AND INTRACELLULAR PH IN EVOLVING BRAIN INFARCT

We examined the relationships between intracellular pH (PH(i)) and interstitial pH (pH(e)) in a rat model of focal ischemia. Interstitial pH was measured with pH-sensitive microelectrodes, and the average tissue pH was measured with the [C-14]dimethadione method in rats subjected to occlusion of the right middle cerebral and common carotid arteries (MCA-CCAO). In normal cortex, pH(e) and pH(i) were 7.24 +/- 0.07 and 7.01 +/- 0.13 (means +/- SD, n = 6), respectively. In the ischemic cortex, pH(e) fell to 6.43 +/- 0.13, whereas pH(i) decreased only to 6.86 +/- 0.11 (n = 5) 1 h after MCA-CCAO. After 4 h of ischemia, the pH(e) was 6.61 +/- 0.09 and pH(i) was 6.62 +/- 0.20 (n = 4). Treatment with glucose before ischemia markedly lowered the pH(e) (5.88 +/- 0.17) but not pH(i) (6.83 +/- 0.03, n = 4) measured 1 h after ischemia. In the ischemic cortex of animals made hypoglycemic by pretreatment with insulin, neither pH(e) (7.25 +/- 0.06) nor pH(i) (6.99 +/- 0.13, n = 4) decreased. The demonstrated difference in pH(i) and pH(e) indicates that some cells remained sufficiently functional to maintain a plasma membrane gradient of protons within the evolving infarct. If the calculated pH(i) values accurately reflect the true pH(i) of cells within zones of severe focal ischemia, then cerebral infarction can proceed at pH(i) levels not greatly altered from normal.