Stroke is a leading cause of disability and death worldwide. There is evidence that there is a circadian rhythm in
stroke with peak occurrence in the morning (6 to 10 am). However, it is not clear if the size of
infarcts and the outcome of
stroke also varies during the 24-hour period. We hypothesized that the size of
cerebral infarct and outcome from
stroke would show circadian variation in a mouse
suture occlusion model. Seven to eight-month-old C57BL/6J (n =10-12 mice/group) mice were randomly assigned to undergo
middle cerebral artery occlusion (MCAO) for 60 minutes at different time points during the 24h day following zeitgeber time at ZT0, ZT6, ZT12, and Z18. Cerebral blood flow was monitored by
Laser Speckle Contrast Imaging at baseline after occlusion, and again at 24h post-occlusion. Neurological deficit was observed by using Bederson score at 24h and 48h. The corner test was used to detect unilateral abnormalities in sensory and motor functions in the
stroke mice at 48h. To estimate
brain infarction, 2,3,5-tryphenyltetrazolium
chloride staining was performed 48h after
stroke and the
infarct area was quantified using NIH-Image J software. We did not find a significant difference in cerebral blood flow at any time point. There was a significant decrease in neurological deficit as assessed using the Bederson Score from 24h (1.82 ± 1.11) to 48h (1.10 ± 0.12) in the ZT18 (midnight) period (p = 0.0025), however there were no differences between groups at 48h. In the corner test, we found right turn preference significantly higher (p = 0.0348) at noon/ZT06 (9.5 ± 1.06) compared to the fully awake (5.5 ± 4.06) (midnight, ZT18) period and ZT0 (6 am, 4.8 ± 0.97, p = 0.0087). Similarly, the
infarction volume was significantly higher (p = 0.0220) during the sleep (ZT06, noon) period (35.22 ± 20.77) than when the ischemic mice were fully awake during the midnight/ZT18 period (15.68 ± 7.54). This is the first report demonstrating that mice have larger
infarcts and worse short-term outcomes during their sleep period (noon/ZT06) than during their awake period (midnight/ZT18).