Abstract WMP118: Preclinical Evaluation Of Circadian Rhythm In Ischemic Stroke Outcomes

Abstract

Background: 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 outcomes of stroke also varies during the 24 hour period Hypothesis: We hypothesized that the size of cerebral infarct and outcome from stroke would show circadian variation in a mouse suture occlusion model. Methods: Seven to eight-month-old C57BL/6J (Wild Type, n=10-15 mice/group) mice were randomly assigned to do stroke at the different time points of the day following zeitgeber time at ZT0, ZT6, ZT12, and Z18. Cerebral Ischemia was induced by occlusion of the middle cerebral artery (MCAO) for 60 min. Blood flow was monitored by Laser Speckle before, after occlusion, and at 24h. Neurological deficit was observed by using Bederson score at 24h and 48h. The corner test was used to detect unilateral abnormalities of sensory and motor functions in the stroke mice at 48h. TTC staining was done, 48 hours after stroke, to estimate brain infarction, and the infarct area was measured by using NIH-Image J software. Results: We did not find a significant difference in CBF at any time points. There was a significant increased ( p <0.05) neurological deficit (Bederson score) at 48h during deep sleep period (ZT6, noon) stroke (1.55±0.17) in comparison to fully awake period stroke (1.1±0.1). In the corner test, we found right turn preference significantly higher ( p <0.005) at noon/ZT6 (9.5±0.34) compared to the fully awake (5.5±0.34) (midnight, ZT18) period. Similarly, the infarction volume was significantly higher ( p <0.05) during the sleep (ZT6, noon) period (29.32±5.03) in comparison to a fully awake midnight/ZT18 period (15.68±2.38). Conclusion: This is the first report demonstrating that mice have larger infarcts and worse short term outcomes during their sleep period (noon/ZT6) than during their awake period (midnight/ZT18).