Circadian Rhythm Disturbance and Stroke Risk

The results of a recent study seem to show that disruption of the circadian rhythm may interact with biological sex to raise or lower the risk of stroke. Published in the journal Endocrinology, the study was conducted by David Earnest, PhD, of the Department of Neuroscience and Experimental Therapeutics at Texas A&M Health Science Center, and colleagues.

Although there has been a significant amount of research showing that disruption of circadian rhythms can affect coronary health, blood pressure, hyperglycemia, and cerebro-vascular disease, among other things, the authors say “little is known about how circadian disturbances affect stroke severity.” They add that nonmodifiable risk factors such as age and sex, when combined with circadian rhythm disruption may “modulate the pathological effects of stroke.”

Thus, the researchers aimed to use an MCAo-induced model fo ischemic stroke to find out how much circadian rhythm disruption impacts stroke severity, and whether or not biological sex changes that impact.

The began by exposing rats to a 12:12 light-dark (LD) pattern for 12 weeks. Then, the animals were divided into 2 groups, one on a fixed LD 12:12 cyclen and the other on a shifted cycle. On the shifted cycle, “the lights-on was advanced by 12hr every 5 days for 7 weeks,” said the researchers. After that, both groups underwent experimental ischemic stroke surgeries at about the same times in their circadian cycles.

The rats in the fixed cycle continued to do things at the same times, for example, the researchers say, “their daily onsets of activity consistently occurred around 5-15 minutes after lights-off.” However, the animals in the shifted group “were distinguished by desynchronized patterns of wheel-running behavior” was different day-to-day. However, both groups ran on the wheels for about the same amount of time each day.

The female rats in the fixed LD group continued to have regular estrous cycles, but the researchers say, for those in the shifted group, “cyclicity was completely abolished and smears were indicative of persistent estrus in all shifted LD animals.” They also found that mortality was higher for males in the shifted group, and that survival times were lower. In fact, the mortality rate for males in the shifted group was 70% following surgery and survival time was 1 day.

“The specific mechanisms by which circadian disturbances affect stroke severity and interact with other nonmodifiable risk factors to modulate the pathological effects of stroke are unknown,” say the researchers. However, future studies “will yield novel insight into the pathophysiological changes in endocrine signals, cytokines, and growth factors that linke disordered circadian clocks to cerebrovascular disease,” they conclude.