Pronounced hypoperfusion during spreading depression in mouse cortex.
We studied unique cerebral blood flow (CBF) responses to cortical spreading depression in mice using a novel two-dimensional CBF imaging technique, laser speckle flowmetry. Cortical spreading depression caused a triphasic CBF response in both rat and mouse cortex. In rats, mild initial hypoperfusion (approximately 75% of baseline) was followed by a transient hyperemia reaching approximately 220% of baseline. In mice, the initial hypoperfusion was pronounced (40-50% of baseline), and the anticipated hyperemic phase barely reached baseline. The duration of hypoperfusion significantly correlated with the duration of the DC shift. As a possible explanation for the pronounced hypoperfusion, mouse cerebral vessels showed enhanced resistance to relaxation by acetylcholine (3 microM) after K+ -induced preconstriction (20, 40, and 80 mM) but dilated normally in response to acetylcholine after preconstriction with U46619, a synthetic thromboxane A2 analog. By contrast, rat vessels dilated readily to acetylcholine after preconstriction by K+. The transient normalization of CBF after hypoperfusion in the mouse was abolished by L-NA but not 7-NI. In summary, the CBF response to cortical spreading depression in mice contrasts with the rat in that the initial hypoperfusion is pronounced, and the hyperemic phase is markedly diminished. The differences in CBF response between species may be in part caused by an increased sensitivity of mouse cerebral vessels to elevated extracellular K+.
Ayata
Cenk
C
Stroke and Neurovascular Regulation Laboratory, Department of Radiology, Harvard Medical School, Charlestown, Massachusetts, 02129, USA. cayata@partners.org
Shin
Hwa Kyoung
HK
Salomone
Salvatore
S
Ozdemir-Gursoy
Yasemin
Y
Boas
David A
DA
Dunn
Andrew K
AK
Moskowitz
Michael A
MA
D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000098:blood supply* / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D013181:Cortical Spreading Depression / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017078:Laser-Doppler Flowmetry; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D019001:Nitric Oxide Synthase; D011188:Potassium