Proton transfer ratio, lactate, and intracellular pH in acute cerebral ischemia

Abstract

The amide proton transfer ratio (APTR) from the asymmetry of the Z-spectrum was determined in rat brain tissue during and after unilateral middle cerebral artery occlusion (MCAo). Cerebral lactate (Lac) as determined by (1)H NMR spectroscopy, water diffusion, and T(1rho) were quantified as well. Lac concentrations were used to estimate intracellular pH (pH(i)) in the brain during the MCA occlusion. A decrease in APTR during occlusion indicated acidification from 7.1 to 6.79 +/- 0.19 (a drop by 0.3 +/- 0.2 pH units), whereas pH(i) computed from Lac concentration was 6.3 +/- 0.2 (a drop by 0.8 +/- 0.2 pH units). Despite the disagreement between the two methods in terms of the size of the change in the absolute pH(i) during ischemia, DeltaAPTR and pH(i) (and Lac concentration) displayed a strong correlation during the MCAo. Diffusion and T(1rho) indicated cytotoxic edema following MCA occlusion; however, APTR returned slowly toward the values determined in the contralateral hemisphere post-ischemia. These data argue that the APTR during ischemia is affected not only by pH(i) but by other physicochemical factors as well, and indicates different aspects of pathology in the post-ischemic brain compared to those that influence water diffusion and T(1rho).