Implications of Circadian Rhythm in Stroke Occurrence: Certainties and Possibilities

Abstract

Stroke occurrence is not randomly distributed over time but has circadian rhythmicity with the highest frequency of onset in the morning hours. This specific temporal pattern is valid for all subtypes of cerebral infarction and intracerebral hemorrhage. It also correlates with the circadian variation of some exogenous factors such as orthostatic changes, physical activity, sleep-awake cycle, as well as with endogenous factors including dipping patterns of blood pressure, or morning prothrombotic and hypofibrinolytic states with underlying cyclic changes in the autonomous system and humoral activity. Since the internal clock is responsible for these circadian biological changes, its disruption may increase the risk of stroke occurrence and influence neuronal susceptibility to injury and neurorehabilitation. This review aims to summarize the literature data on the circadian variation of cerebrovascular events according to physiological, cellular, and molecular circadian changes, to survey the available information on the chronotherapy and chronoprophylaxis of stroke and its risk factors, as well as to discuss the less reviewed impact of the circadian rhythm in stroke onset on patient outcome and functional status after stroke.

Study of Brain Circadian Rhythms in Patients with Chronic Disorders of Consciousness and Healthy Individuals Using Microwave Radiometry

“…Brain damage can lead to disturbances in cerebral circadian rhythms, which was demonstrated using temperature sensors implanted in the brain parenchyma. A better outcome was shown in patients with preserved circadian rhythm and higher mesor (mean level) values, [ 6 , 7 ] which coincides with another study with similar results in half of the patients after severe traumatic brain injury (TBI) with maintained circadian rhythm of cerebral and body temperature [ 8 , 9 ]. These studies emphasize the importance of circadian rhythms, the presence of which reflects the higher potential of one’s own reparative responses.…”

Relationship between circadian syndrome and stroke: A cross-sectional study of the national health and nutrition examination survey

“…Some poor lifestyles, including sleep disturbances, the use of artificial light, and shift work, have been reported to cause the circadian rhythm disturbances, which have adverse effects on human health ( 7 ). Recently, a growing number of studies have focused on the relationship between the circadian system and chronic diseases ( 8 – 10 ). Circadian dysfunction has been proposed and defined as the presence of any four of the following seven traits, including elevated waist circumference, elevated triglycerides, reduced high-density lipoprotein (HDL)-cholesterol, elevated blood pressure, elevated fasting glucose, short sleep duration (<6 h/day), and the depression symptom ( 7 ).…”

New insight into ischemic stroke: Circadian rhythm in post-stroke angiogenesis

“…It is now known that the incidence of myocardial infarction and ischemic stroke occurs significantly more often in the morning, while respiratory and other inflammatory diseases tend to become exacerbated at night ( Paschos and FitzGerald, 2010 ; Tsimakouridze et al, 2015 ). The influence of circadian rhythms on stroke is first manifested in the difference in stroke onset time: the incidence of stroke increases significantly between 6 a.m. and 12 p.m., and the frequency of onset of hemispheric stroke was significantly ( p = 0.0001) higher between 6:01 a.m. and 12:00 p.m. (56.1%) than between 12:01 and 6 p.m. (20.2%), 6:01 p.m. and 12:00 a.m. (8.2%), and 12:01 and 6 a.m. (15.5%) ( Chaturvedi et al, 1999 ; Ripamonti et al, 2017 ; Fodor et al, 2021 ). With the deepening of research, the environmental circadian disruption (ECD) model, induced by 6-h phase advances of the light cycle each week for 6 weeks, is widely used in the research of circadian rhythms ( Sellix et al, 2012 ; Hill et al, 2021 ).…”

“…The core clock genes widely distributed across the brain affect most fundamental physiological processes, including the trigger factors of stroke, such as arterial blood pressure, heart rate, coagulation balance, and other rhythmic events ( Li et al, 2013 ; Fodor et al, 2021 ). In recent years, with the increasing application of ambulatory blood pressure monitoring (ABPM) in stroke research, more and more evidence indicates that circadian blood pressure is closely related to the incidence of stroke, an especially circadian rhythm disturbance of blood pressure as an independent risk factor for stroke ( Pierdomenico et al, 2016 ; Cai et al, 2017 ).…”

“…As previously described, internal circadian dysregulation may contribute to the incidence of stroke; conversely, the stroke itself can lead to the desynchronization of endogenous circadian rhythms by directly affecting the SCN, or by disrupting the clock mechanisms of neurons, glia, and endothelial cells ( Kostenko and Petrova, 2018 ; Fodor et al, 2021 ). Clinically, strokes are positively related to anxiety-depressive and affective disorders, and are accompanied by a high frequency of sleep disorders, and desynchronization in daily curves of the heart rate (HR) and blood pressure (BP) ( Jain et al, 2004 ; Hidehiro et al, 2007 ; Kostenko and Petrova, 2018 ).…”