title: Sex Differences in the Impact of Shift Work Schedules on Pathological Outcomes in an Animal Model of Ischemic Stroke.
abstract: Circadian clock desynchronization has been implicated in the pathophysiology of cardiovascular disease and related risk factors (eg, obesity, diabetes). Thus, we examined the extent to which circadian desynchronization exacerbates ischemic stroke outcomes and whether its detrimental effects on stroke severity and functional impairments are further modified by biological sex. Circadian entrainment of activity rhythms in all male and female rats was observed during exposure to a fixed light-dark (LD) 12:12 cycle but was severely disrupted when this LD cycle was routinely shifted (12 h advance/5 d) for approximately 7 weeks. In contrast to the regular estrous cycles in fixed LD animals, cyclicity was abolished and persistent estrus was evident in all shifted LD females. The disruption of estrous cyclicity in shifted LD females was associated with a significant increase in serum estradiol levels relative to that observed in fixed LD controls. Circadian rhythm disruption exacerbated stroke outcomes in both shifted LD male and female rats and further amplified sex differences in stroke impairments. In males, but not females, circadian disruption after exposure to the shifted LD cycle was marked by high rates of mortality. In surviving females, circadian desynchronization after exposure to shifted LD cycles produced significant increases in stroke-induced infarct volume and sensorimotor deficits with corresponding decreases in serum IGF-1 levels. These results suggest that circadian rhythm disruption associated with shift work schedules or the irregular nature of our everyday work and/or social environments may interact with other nonmodifiable risk factors such as biological sex to modulate the pathological effects of stroke.
authors.affiliation: Department of Neuroscience and Experimental Therapeutics (D.J.E., N.N., J.C., A.S., F.S.) and Women's Health in Neuroscience Program (A.S., F.S.), Texas A&M Health Science Center, College of Medicine, Bryan, Texas 77807-3260; and Department of Biology (D.J.E.) and Center for Biological Clocks Research (D.J.E.), Texas A&M University, College Station, Texas 77843-3258.
authors.forename: David J
authors.initials: DJ
authors.lastname: Earnest
authors.affiliation: Department of Neuroscience and Experimental Therapeutics (D.J.E., N.N., J.C., A.S., F.S.) and Women's Health in Neuroscience Program (A.S., F.S.), Texas A&M Health Science Center, College of Medicine, Bryan, Texas 77807-3260; and Department of Biology (D.J.E.) and Center for Biological Clocks Research (D.J.E.), Texas A&M University, College Station, Texas 77843-3258.
authors.forename: Nichole
authors.initials: N
authors.lastname: Neuendorff
authors.affiliation: Department of Neuroscience and Experimental Therapeutics (D.J.E., N.N., J.C., A.S., F.S.) and Women's Health in Neuroscience Program (A.S., F.S.), Texas A&M Health Science Center, College of Medicine, Bryan, Texas 77807-3260; and Department of Biology (D.J.E.) and Center for Biological Clocks Research (D.J.E.), Texas A&M University, College Station, Texas 77843-3258.
authors.forename: Jason
authors.initials: J
authors.lastname: Coffman
authors.affiliation: Department of Neuroscience and Experimental Therapeutics (D.J.E., N.N., J.C., A.S., F.S.) and Women's Health in Neuroscience Program (A.S., F.S.), Texas A&M Health Science Center, College of Medicine, Bryan, Texas 77807-3260; and Department of Biology (D.J.E.) and Center for Biological Clocks Research (D.J.E.), Texas A&M University, College Station, Texas 77843-3258.
authors.forename: Amutha
authors.initials: A
authors.lastname: Selvamani
authors.affiliation: Department of Neuroscience and Experimental Therapeutics (D.J.E., N.N., J.C., A.S., F.S.) and Women's Health in Neuroscience Program (A.S., F.S.), Texas A&M Health Science Center, College of Medicine, Bryan, Texas 77807-3260; and Department of Biology (D.J.E.) and Center for Biological Clocks Research (D.J.E.), Texas A&M University, College Station, Texas 77843-3258.
authors.forename: Farida
authors.initials: F
authors.lastname: Sohrabji
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000473:pathology* / Q000503:physiopathology; D002940:Circadian Rhythm / Q000502:physiology*; D004195:Disease Models, Animal; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D008297:Male; D009043:Motor Activity / Q000502:physiology; D017440:Photoperiod; D051381:Rats; D012727:Sex Characteristics; D012931:Social Environment; D020521:Stroke / Q000473:pathology* / Q000503:physiopathology