Glucose metabolism and acidosis in the metabolic penumbra of rat brain

The characterization of tissue acid-base status related to the penumbral zone of increased glucose consumption surrounding a focal cerebral ischemic lesion may suggest therapeutic techniques to maximize tissue survivability from stoke. We measured local cerebral metabolic rate for glucose (l CMRglc) and an index of brain tissue pH (pH_t) concurrently and characterized their interaction in a model of focal cerebral ischemia in rats in a double-label autoradiographic study, using [¹⁴C]2-deoxyglucose and [¹⁴C]dimethyloxazolidinedione. Computer-assisted digitization and analysis permitted the simultaneous quantification of the two variables on a pixel-by-pixel basis in the same brain slices. Hemispheres ipsilateral to intravascular tamponade-induced middle cerebral artery occlusion showed areas of normal, depressed, and elevated glucose metabolic rate (as defined by an interhemispheric asymmetry index) after 2 hr of ischemia. Regions of increased l CMRglc showed moderate acidosis (6.87±0.05), while regions of normal glucose metabolic rate showed normal pH_t (pH±SD=6.98 ± 0.05) and regions of decreased l CMRglc showed severe acidosis (6.69±0.11). A repeated-measures analysis of variance found these values to differ from each other at the P < 0.0005 significance level. The finding of moderate acidosis coupled with increased l CRMglc in the metabolic penumbra suggests that the excess protons may result from the anaerobic dissociation of ATP synthesis and hydrolysis.