Cortical spreading depression impairs oxygen delivery and metabolism in mice.
Cortical spreading depression (CSD) is associated with severe hypoperfusion in mice. Using minimally invasive multimodal optical imaging, we show that severe flow reductions during and after spreading depression are associated with a steep decline in cerebral metabolic rate of oxygen. Concurrent severe hemoglobin desaturation suggests that the oxygen metabolism becomes at least in part supply limited, and the decrease in cortical blood volume implicates vasoconstriction as the mechanism. In support of oxygen supply-demand mismatch, cortical nicotinamide adenine dinucleotide (NADH) fluorescence increases during spreading depression for at least 5 minutes, particularly away from parenchymal arterioles. However, modeling of tissue oxygen delivery shows that cerebral metabolic rate of oxygen drops more than predicted by a purely supply-limited model, raising the possibility of a concurrent reduction in oxygen demand during spreading depression. Importantly, a subsequent spreading depression triggered within 15 minutes evokes a monophasic flow increase superimposed on the oligemic baseline, which markedly differs from the response to the preceding spreading depression triggered in naive cortex. Altogether, these data suggest that CSD is associated with long-lasting oxygen supply-demand mismatch linked to severe vasoconstriction in mice.
Department of Radiology, Neurovascular Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
Izumi
I
Yuzawa
Sava
S
Sakadžić
Vivek J
VJ
Srinivasan
Hwa Kyoung
HK
Shin
Katharina
K
Eikermann-Haerter
David A
DA
Boas
Cenk
C
Ayata
D000818:Animals; D001810:Blood Volume; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D013181:Cortical Spreading Depression; D005260:Female; D006439:Hemodynamics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D036641:Microscopy, Fluorescence, Multiphoton; D009243:NAD / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*
D009243:NAD; D010100:Oxygen