Repetitive concentric wave-ring spread of oligemia/hyperemia in the sensorimotor cortex accompanying K+-induced spreading depression in rats and cats

Self Cite

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 Â 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.

Section: General Description Of Cortical Spreading Depressionsupporting

confidence: 80%

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

Tomita

Schiszler

Tsutsumi³

et al. 2005

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“…*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.…”

Section: Discussionsupporting

confidence: 66%

“…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.…”

Section: Discussionsupporting

confidence: 58%

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

Sukhotinsky

Dileköz

Moskowitz

et al. 2008

Cortical spreading depression (CSD) evokes a large cerebral blood flow (CBF) increase in normal rat brain. In contrast, in focal ischemic penumbra, CSD-like periinfarct depolarizations (PID) are mainly associated with hypoperfusion. Because PIDs electrophysiologically closely resemble CSD, we tested whether conditions present in ischemic penumbra, such as tissue hypoxia or reduced perfusion pressure, transform the CSD-induced CBF response in nonischemic rat cortex. Cerebral blood flow changes were recorded using laser Doppler flowmetry in rats subjected to hypoxia, hypotension, or both. Under normoxic normotensive conditions, CSD caused a characteristic transient CBF increase (74±7%) occasionally preceded by a small hypoperfusion (À4±2%). Both hypoxia (pO 2 45 ± 3 mm Hg) and hypotension (blood pressure 42 ± 2 mm Hg) independently augmented this initial hypoperfusion (À14±2% normoxic hypotension; À16±6% hypoxic normotension; À21 ± 5% hypoxic hypotension) and diminished the magnitude of hyperemia (44±10% normoxic hypotension; 43±9% hypoxic normotension; 27±6% hypoxic hypotension). Hypotension and, to a much lesser extent, hypoxia increased the duration of hypoperfusion and the DC shift, whereas CSD amplitude remained unchanged. These results suggest that hypoxia and/or hypotension unmask a vasoconstrictive response during CSD in the rat such that, under nonphysiologic conditions (i.e., mimicking ischemic penumbra), the hyperemic response to CSD becomes attenuated resembling the blood flow response during PIDs.

“…Waves typically crossed all 25 analyzed ROIs, and we suspect that they spread over the entire cortex. Concentric wave propagation of CSDs has been described in rats and cats under physiological conditions after induction with high potassium (Farkas et al, 2008;Smith et al, 2001;Tomita et al, 2002). In focal ischemia, in contrast, rostral-caudal or circumferential propagation around the ischemic core seems to be the predominant pattern (Hartings et al, 2003;Luckl et al, 2009;Nakamura et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Distinct Spatiotemporal Patterns of Spreading Depolarizations during Early Infarct Evolution: Evidence from Real-Time Imaging

Kumagai

Walberer

Nakamura

et al. 2010

Experimental and clinical studies indicate that waves of cortical spreading depolarization (CSD) appearing in the ischemic penumbra contribute to secondary lesion growth. We used an embolic stroke model that enabled us to investigate inverse coupling of blood flow by laser speckle imaging (CBF LSF ) to CSD as a contributing factor to lesion growth already in the early phase after arterial occlusion. Embolization by macrospheres injected into the left carotid artery of anesthetized rats reduced CBF LSF in the territories of the middle cerebral artery (MCA) (8/14 animals), the posterior cerebral artery (PCA) (2/14) or in less clearly defined regions (4/14). Analysis of MCA occlusions (MCAOs) revealed a first CSD wave starting off during ischemic decline at the emerging core region, propagating concentrically over large portions of left cortex. Subsequent recurrent waves of CSD did not propagate concentrically but preferentially circled around the ischemic core. In the vicinity of the core region, CSDs were coupled to waves of predominantly vasoconstrictive CBF LSF responses, resulting in further decline of CBF in the entire inner penumbra and in expansion of the ischemic core. We conclude that CSDs and corresponding CBF responses follow a defined spatiotemporal order, and contribute to early evolution of ischemic territories.