Long-Lasting Reduction of Cortical Blood Flow of the Rat Brain after Spreading Depression with Preserved Autoregulation and Impaired CO2 Response

Abstract

The purpose of the present study was to examine the cerebral perfusion after spreading depression with special emphasis on its relation to the perfusion changes in migraine. The cerebrovascular reactivity to changes of arterial Pco2 tension in the range of 24–70 mm Hg and to changes of MABP in the range of 55–150 mm Hg was studied in the rat brain after one episode of cortical spreading depression. Regional CBF (rCBF) was measured in the frontal, parietal, and occipital cortex, the basal ganglia, and the cerebellum of both hemispheres after the intravenous bolus injection of [14C]iodoantipyrine. rCBF decreased in the cortical regions to 69–73% of control values for 1 h after spreading depression in every single rat, but remained unchanged in the basal ganglia and cerebellum. CBF changed with alterations of arterial carbon dioxide tension in all brain regions. In control regions, CBF changed by 2.8–3.9% per mm Hg Paco2 change, whereas in the spreading depression cortex, CBF changed by only 1.3–1.5%. The difference between control and spreading depression cortex was significant at p < 0.001, indicating a reduced CO2 sensitivity of the cortical regions invaded by spreading depression. rCBF remained unchanged in all brain regions in the MABP range of 80–150 mm Hg, reflecting the intact autoregulatory function of the two sides, and at a MABP of <80 mm Hg, rCBF decreased in parallel in symmetrical regions. It is concluded that the hypoperfusion after spreading depression is due to a vasoconstrictor stimulus overriding the vasodilatory effect of acid pH. The reduced CO2 response is probably the effect and not the cause of this vasoconstriction. The coexistence of rCBF reduction with perserved autoregulation and impaired CO2 response in an otherwise normally perfused brain has previously been found in patients during migraine attacks. This study therefore corroborates the notion that the perfusion changes of migraine may be pathophysiologically related to spreading depression and that spreading depression may serve as an experimental model of migraine.