Initial Oligemia with Capillary Flow Stop Followed by Hyperemia during K⁺-Induced Cortical Spreading Depression in Rats

Abstract

Local cerebral blood volume (CBV) and capillary flow changes in regions of depolarizing neurons during K þ -induced cortical spreading depression (CSD) in the cerebral cortex of a-chloraloseurethane-anesthetized rats were examined employing a transillumination (550 nm) video system. Capillary flow was calculated as the reciprocal of mean transit times of blood in pixels of 40 lm  40 lm, each of which contains a few capillaries. Potassium microinjection into the cortex evoked repetitive wave-ring spreads of oligemia at a speed of ca. 2.3370.48 mm/min. During the spread of CSD, tracer (either saline or carbon black) was injected into the internal carotid artery. Colocated with the oligemic wave, we detected capillary flow stop as evidenced by disappearance of the hemodilution curves. At any location in the region of interest within the cerebral cortex, we observed cyclic changes of capillary flow stop/hyperperfusion in synchrony with oligemia/ hyperemia fluctuations. The initial flow stop and oligemia were ascribed to capillary compression by astroglial cell swelling, presumably at the pericapillary endfeet, since the oligemia occurred before larger vessel changes. We conclude that local depolarizing neurons can decrease adjacent capillary flow directly and immediately, most likely via astroglial cell swelling, and that the flow stop triggers upstream arteriolar dilatation for capillary hyperperfusion.

Hypoxia and Hypotension Transform the Blood Flow Response to Cortical Spreading Depression from Hyperemia into Hypoperfusion in the Rat

“…Under nonphysiologic conditions, such as systemic hypoxia and reduced cerebral perfusion pressure, the vasoconstrictive response can be augmented and become the predominant response to CSD, as previously reported in response to CSD during focal and global ischemia (Shin et al, 2006;Sonn and Mayevsky, 2000;Strong et al, 2007). The observed variability of hypoperfusion response to CSD in previous studies (Ayata et al, 2004;Bures and Buresova, 1956;Duckrow, 1993;Fabricius et al, 1995;Farkas et al, 2007;Lauritzen, 1987;Mayevsky et al, 1998;Osada et al, 2006;Piper et al, 1991;Sonn and Mayevsky, 2000;Tomita et al, 2002Tomita et al, , 2005Van Harreveld and Stamm, 1952;Van Harreveld and Ochs, 1957) may thus be related to differences in baseline systemic physiology (pO 2 , BP), choice of anesthesia, species, and the caliber of vessels from which the recordings are obtained.…”

“…*P < 0.01 versus normoxic normotension and hypoxic normotension; w P < 0.01 versus normoxic normotension. Under normoxic normotensive conditions, the characteristic large hyperemia is often preceded by a small hypoperfusion, as previously described in anesthetized rats, rabbits, and cats (Ayata et al, 2004;Fabricius et al, 1995;Osada et al, 2006;Tomita et al, 2002Tomita et al, , 2005Van Harreveld and Stamm, 1952), suggesting that CSD causes vasoconstriction followed by vasodilation. More recently, selective measurements of arterial diameter in 15-to 25-day-old rats show heterogeneous vasomotor responses to CSD depending on the vessel caliber.…”

“…This profound CBF increase starts late during the depolarization phase and outlasts it by a few minutes (Ayata et al, 2004;Bures and Buresova, 1956;Farkas et al, 2007;Lauritzen, 1987;Mayevsky et al, 1998;Piper et al, 1991;Sonn and Mayevsky, 2000). A brief vasoconstriction occasionally precedes the vasodilation leading to an initial small hypoperfusion (Ayata et al, 2004;Osada et al, 2006;Tomita et al, 2002Tomita et al, , 2005Van Harreveld and Stamm, 1952;Van Harreveld and Ochs, 1957), which is augmented by nitric oxide (NO) inhibition (Duckrow, 1993;Fabricius et al, 1995), particularly when [K + ] e is artificially elevated (Dreier et al, 1998). Published data also suggest that partial tissue ischemia augments the initial vasoconstriction and diminishes vasodilation, as observed during hypoxia, after bilateral carotid occlusion and in focal ischemic penumbra (Shin et al, 2006;Sonn and Mayevsky, 2000;Strong et al, 2007).…”

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

“…When neuronal-vascular coupling is so prevented, the stimulus-induced P O2 decrease ('dip') is enhanced and prolonged, resembling in vitro conditions [59]. In the case of SD, hyperemia predominates while neurons are depolarized but this is usually followed by prolonged hypo-perfusion [72][73][74][75][76][77][78]. The late hypo-perfusion following SD can cause delayed reduction of NADH-NAD + [44].…”

High-ResolutionIn VivoImaging of the Neurovascular Unit during Spreading Depression

“…Recently, astrocytic calcium has been linked to motion of vessels (Zonta et al, 2003;Filosa et al, 2004;Mulligan and MacVicar, 2004;Metea and Newman, 2006); the astrocytic wave of SD could therefore affect blood flow (Mulligan and MacVicar, 2004). Several laser Doppler flowmetry (LDF) studies observed that, occasionally in rats Dreier et al, 2001;Ayata et al, 2004;Tomita et al, 2005) and mice (Ayata et al, 2004), a brief hypoperfusion precedes the large transient hyperemia in SD. This can become a deleterious ischemia when nitric oxide is blocked or extracellular [K ϩ ] is artificially elevated (Dreier et al, 2001).…”