Time matters: Circadian effects on stroke pathophysiology

In the last three decades, a huge amount of data and number of reports have proved that ischemic brain damage develops differently based on the time of the day at which it occurs. Differences in circadian rhythms between nocturnal rodent models and diurnal humans may explain the lost in translation crisis experienced in the stroke field. To clarify aspects related to circadian rhythm in stroke and to maximize the translatability of preclinical studies in the attempt to identify new promising therapeutic strategies in stroke, changes in biomarkers and systemic biology have been studied after stroke induction in mice. Circadian rhythms influence the metabolic response to stroke in the brain and in the peripheral blood and muscles, with greater efficacy observed during the rodent inactive phase. In the present review article, we intend to summarize the main findings recently published in the field with the attempt to underline the importance of studying the circadian timing in stroke research in order to improve the translation of brain protective strategies from animals to humans.