Spreading depression reversibly impairs autoregulation of cortical blood flow

Abstract

The experiment examines whether the mechanisms responsible for the autoregulation of cerebral blood flow (CBF) in response to hypotension were affected during the initial phase of cortical spreading depression (CSD). CSD was induced by a cortical pinprick in anesthetized rabbits, and CBF was measured by laser-Doppler flowmetry through a chronically implanted Plexiglas window. The reactivity to CO2 and papaverine was also studied before and after CSD. Fifteen minutes after CSD, autoregulatory vasodilation was reduced (P < 0.01). This impairment was reversible, since the autoregulatory response was restored 35 min after CSD. The time course of the reactivity to papaverine after CSD paralleled the autoregulatory response, with a significant correlation between the two reactivities (r = 0.47; P < 0.01). Conversely, the reactivity to CO2 was significantly reduced after CSD (P < 0.001) and remained affected for at least 95 min. We conclude that the mechanisms underlying autoregulation are transiently disturbed by CSD and that these mechanisms are not mediated by an accumulation of CO2 but seem instead to be related to an increase in adenosine 3',5'-cyclic monophosphate concentration.

Is the Acetazolamide Test Valid for Quantitative Assessment of Maximal Cerebral Autoregulatory Vasodilation?

“…12 Changes in PaCO 2 affect CVR since an increase in PaCO 2 results in an increase in CBF. This parallelism between ACZ and CO 2 effects is con- 15 demonstrated in anesthetized rabbits that spreading depression reversibly impairs cerebral autoregulatory vasodilation but, in contrast, induces a longlasting decrease in the cerebrovascular reactivity to CO 2 . In contrast, other reports suggest that CO 2 interacts with autoregulation, which can even be exhausted during hypercapnia.…”

Spreading Depression, Spreading Depolarizations, and the Cerebral Vasculature

“…Indeed, isolated vessels harvested after they were exposed to an SD in situ showed much diminished reactivity to pH and [K ϩ ] o changes (415). Even the response to the direct vasodilator papaverine appeared to be diminished after an SD in one study (130), although responses to acetylcholine, CGRP, NMDA, K ATP channel opener aprikalim, and adenylate cyclase activator forskolin were reportedly preserved after SD in rabbits (46, 80), suggesting that the vasomotor paralysis may not apply to all species or mediators.…”

CO 2 Reactivity Measured by Perfusion MRI During Transient Focal Cerebral Ischemia in Rats

“…The other possible explanation relates to spreading depression, which occurs shortly after ischemia 31 and results in a long-lasting reduction of cortical blood flow with impaired CO 2 response. 27,32 There was no difference in CO 2 response during MCAO between areas that were permanently damaged and those that recovered. This means that the CO 2 reactivity during MCAO cannot be used to predict the outcome after 4.5 hours of reperfusion.…”