Metabolic and Hemodynamic Activation of Postischemic Rat Brain by Cortical Spreading Depression

Abstract

Following transient ischemia of the brain, the coupling between somatosensory activation and the hemodynamic-metabolic response is abolished for a certain period despite the partial recovery of somatosensory evoked responses. To determine whether this disturbance is due to alterations of the stimulus-induced neuronal excitation or to a breakdown of the coupling mechanisms, cortical spreading depression was used as a metabolic stimulus in rats before and after ischemia. Adult rats were subjected to 30 min of global forebrain ischemia and 3–6 h of recirculation. EEG, cortical direct current (DC) potential, and laser-Doppler flow were continuously recorded. Local CBF (LCBF), local CMR_glc (LCMR_glc), regional tissue contents of ATP, glucose, and lactate, and regional pH were determined by quantitative autoradiography, substrate-induced bioluminescence, and fluorometry. Amplitude and frequency of the DC shifts did not differ between groups. In control animals, spreading depression induced a 77% rise in cortical glucose consumption, a 66% rise in lactate content, and a drop in tissue pH of 0.3 unit. ATP and glucose contents were not depleted. During the passage of DC shifts, transient increases (glc was depressed after ischemia, it was activated 47% during spreading depression. Lactate increased by 26%, pH decreased by 0.3 unit, and ATP and glucose remained unchanged. The extent of the transient increase in laser-Doppler flow did not differ from that of the control group, and a post–spreading depression hypoperfusion was also found. The results demonstrate that the postischemic brain may, although to a lesser degree, cover additional energy demands. The previously observed suppression of functional activation after ischemia is probably caused by both alterations in afferent synaptic transmission and subsequent neuronal excitation and the diminution of the metabolic response to a local stimulus as observed during spreading depression.