Changes in Vascular and Metabolic Reactivity as Indices of Ischaemia in the Penumbra

Abstract

The reactivities of cerebral cortical blood flow (hydrogen clearance) and of compensated NADH fluorescence to local cortical electrical stimulation were examined on the marginal gyrus before and after transorbital occlusion of the middle cerebral artery in cats. Prestimulus cerebral blood flow (CBF) was 38.2 ± 12.9 (SD) ml 100 g−1 min−1 and fell to 19.8 ± 11.1 following occlusion (p < 0.02). Peak hydrogen clearance rate (percent increase above prestimulus clearance) was 81.6 ± 53.6 and fell to 19.9 ± 29.8 after middle cerebral artery occlusion (p < 0.01). Steady-state NADH fluorescence rose from 33.5 ± 10.7 to 40.5 ± 17.6% full-scale deflection following MCAO (p < 0.01). Latency from stimulus to maximal fluorescence depression in response to cortical stimulation increased from 12.2 ± 8.2 to 22.1 ± 11.9 s (p < 0.01). Hyperaemic responses at anteromedial sites on the marginal gyrus significantly exceeded those at posterolateral sites. The results are interpreted as indicating early ischaemic metabolic change; however, the presence of residual vasodilator responses to stimulation suggests that flow reduction and early ischaemic change in the territory studied are not simply due to inadequate collateral input, but may also reflect deafferentation or functional suppression. The possible significance of diminished vascular reactivity in the penumbra as a cause of increased vulnerability to extracellular release of excitatory amino acids is discussed.

Differences in O2 availability resolve the apparent discrepancies in metabolic intrinsic optical signals in vivo and in vitro

“…Numerous reports confirmed that neuronal excitation in intact brain was accompanied by sustained oxidation of NADH [19,30,[34][35][36][37][38][39][40][41][42][43][44][45]. A close correlation was also observed between NADH oxidation and oxygen consumption in cat and rat neocortex [46,47].…”

Cortical spreading depression: an adverse but treatable factor in intensive care?

“…The demonstration of impaired vasoreactivity to cortical stimulation in the penumbra [28] and the knowledge that spreading depression is associated with movement of extracellular calcium into cells suggest that cytotoxicity might arise from abnormally sustained increases in cytosolic calcium. Gido and colleagues [29], however, were unable to confirm this.…”

Penumbral Microcirculatory Changes Associated With Peri-infarct Depolarizations in the Rat

“…Since total blood flow in the MCA territory is limited by the diameter of anatomoses, 25 any focal increase in blood flow in this territory is likely to be accompanied by a decrease in perfusion in other parts of the same arterial territory. Strong et al 26 showed that stimulation of a cortical area within the MCA territory after MCAO caused an increase in blood flow in the stimulated area, with a decrease in blood flow in an adjacent region. It is difficult to assess the clinical relevance of the brief enhancement of ischemic conditions by PIDs in the penumbra, since the occurrence of PIDs in humans has not been studied during stroke.…”