1. ^*Stroke and Neurovascular Regulation Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts
2. ^†Stroke Service and Neuroscience Intensive Care Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts
3. ^‡Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts

Correspondence: Cenk Ayata, Stroke and Neurovascular Regulation Laboratory, 149 13th Street, Room 6403, Charlestown, MA 02129; e-mail: cayata@partners.org

Received 9 March 2004; Revised 18 May 2004; Accepted 9 June 2004.

Abstract

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 M) 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⁺.