Subcortical Cerebral Blood Flow and Metabolic Changes Elicited by Cortical Spreading Depression in Rat

Changes in cerebral cortical perfusion (CBFLDF), local cerebral blood flow (ICBF) and local cerebral glucose utilization (ICGU) elicited by unilateral cortical spreading depression (SD) were monitored and measured in separate groups of rats anesthetized with a-chloralose. CBFLDF was recorded with laser Doppler flowmetry, while ICBF and ICGU were measured by the quantitative autoradiographic [14C]iodoantipyrine and [14C]-2-deoxyglucose methods, respectively. SD elicited a wave of hyperemia after a latency of 2 to 3 min followed by an oligemic phase. Ninety minutes following the onset of SD cortical (frontal, parietal and occipital) ICBF and ICGU were essentially the same as on the contralateral side and in sham-treated rats. However, alteration in the ICBF and ICGU in upper and lower brainstem persisted. The present results demonstrate, for the first time, that long-lasting cerebrovascular and metabolic alterations take place within the subcortical regions following SD. These regions provide an attractive site to integrate observations in man concerning spreading depression and the aura of migraine with the other features of the syndrome.

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

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2008.35 ◽

2008 ◽

Vol 28 (7) ◽

pp. 1369-1376 ◽

Cited By ~ 56

Author(s):

Inna Sukhotinsky ◽

Ergin Dilekoz ◽

Michael A Moskowitz ◽

Cenk Ayata

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Cortical Spreading Depression ◽

Spreading Depression ◽

Ischemic Penumbra ◽

Doppler Flowmetry ◽

Blood Flow Response ◽

Flow Response ◽

Normal Rat ◽

Cortex Cérébral

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 (−4 ± 2%). Both hypoxia ( pO2 45 ± 3 mm Hg) and hypotension (blood pressure 42 ± 2 mm Hg) independently augmented this initial hypoperfusion (−14 ± 2% normoxic hypotension; −16 ± 6% hypoxic normotension; −21 ± 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.

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Spreading depression reversibly impairs autoregulation of cortical blood flow

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1994.266.4.r1136 ◽

1994 ◽

Vol 266 (4) ◽

pp. R1136-R1140 ◽

Cited By ~ 2

Author(s):

G. Florence ◽

G. Bonvento ◽

R. Charbonne ◽

J. Seylaz

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Laser Doppler Flowmetry ◽

Initial Phase ◽

Cortical Spreading Depression ◽

Time Course ◽

Spreading Depression ◽

Doppler Flowmetry ◽

Cortical Blood Flow ◽

Before And After

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.

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Amylin: Localization, Effects on Cerebral Arteries and on Local Cerebral Blood Flow in the Cat

The Scientific World JOURNAL ◽

10.1100/tsw.2001.23 ◽

2001 ◽

Vol 1 ◽

pp. 168-180 ◽

Cited By ~ 33

Author(s):

Lars Edvinsson ◽

Peter J. Goadsby ◽

Rolf Uddman

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Blood Vessels ◽

Cerebral Arteries ◽

In Vivo Studies ◽

Cerebral Blood Vessels ◽

Local Cerebral Blood Flow ◽

Doppler Flowmetry

Amylin and adrenomedullin are two peptides structurally related to calcitonin gene-related peptide (CGRP). We studied the occurrence of amylin in trigeminal ganglia and cerebral blood vessels of the cat with immunocytochemistry and evaluated the role of amylin and adrenomedullin in the cerebral circulation by in vitro and in vivo pharmacology. Immunocytochemistry revealed that numerous nerve cell bodies in the trigeminal ganglion contained CGRP immunoreactivity (-ir); some of these also expressed amylin-ir but none adrenomedullin-ir. There were numerous nerve fibres surrounding cerebral blood vessels that contained CGRP-ir. Occasional fibres contained amylin-ir while we observed no adrenomedullin-ir in the vessel walls. With RT-PCR and Real-Time�PCR we revealed the presence of mRNA for calcitonin receptor-like receptor (CLRL) and receptor-activity-modifying proteins (RAMPs) in cat cerebral arteries. In vitro studies revealed that amylin, adrenomedullin, and CGRP relaxed ring segments of the cat middle cerebral artery. CGRP and amylin caused concentration-dependent relaxations at low concentrations of PGF2a-precontracted segment (with or without endothelium) whereas only at high concentration did adrenomedullin cause relaxation. CGRP8-37 blocked the CGRP and amylin induced relaxations in a parallel fashion. In vivo studies of amylin, adrenomedullin, and CGRP showed a brisk reproducible increase in local cerebral blood flow as examined using laser Doppler flowmetry applied to the cerebral cortex of the a-chloralose�anesthetized cat. The responses to amylin and CGRP were blocked by CGRP8-37. The studies suggest that there is a functional sub-set of amylin-containing trigeminal neurons which probably act via CGRP receptors.

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