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

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 H-1 NMR spectroscopy, water diffusion, and T-1 rho were quantified as well. Lac concentrations were used to estimate intracellular pH (pH,) 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, 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, during ischemia, Delta APTR and pH, (and Lac concentration) displayed a strong correlation during the MCAo. Diffusion and T-1 rho, 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-1 rho.