Threshold relationship between cerebral blood flow, glucose utilization, and energy metabolites during development of stroke in gerbils

Abstract

Focal brain ischemia was produced in halothane-anesthetized Mongolian gerbils by occluding the right common and the left external carotid artery. Ninety minutes after vascular occlusion the following regional hemodynamic and metabolic parameters were evaluated in adjacent cryostat sections taken from seven different coronal planes of each brain: cerebral blood flow (CBF), glucose utilization (CMRG), and the tissue content of ATP and glucose. NADH fluorescence was recorded from the surface of the cryostat block. In addition, tissue slices were taken from each brain to determine the rate of phosphorylation of 2-deoxyglucose in ischemic and nonischemic regions. Depending on the density of ischemia, the following metabolic disturbances were observed. At CBF values below 35 ml × 100 g −1 × min −1 CMRG increased and at values below 25 ml × 100 g −1 × min −1 it declined sharply. Glucose content declined when CBF was below 35 ml × 100 g −1 × min −1 and ATP fell at CBF below 20 ml × 100 g −1 × min −1. At 10 ml × 100 g −1 × min −1 ATP was completely depleted. NADH fluorescence was found elevated at flow rates that caused an increase of glucose utilization and was maximal when CBF stopped. The ischemic thresholds for the initial increase in CMRG and the complete depletion of ATP content represent the metabolic equivalent of the penumbra zone and provide a basis for the evaluation of therapeutic procedures for the treatment of stroke.