title: Sleep Is Critical for Remote Preconditioning-Induced Neuroprotection.
abstract: Episodes of brief limb ischemia (remote preconditioning) in mice induce tolerance to modeled ischemic stroke (focal brain ischemia). Since stroke outcomes are in part dependent on sleep-wake history, we sought to determine if sleep is critical for the neuroprotective effect of limb ischemia.
  
  
  
  EEG/EMG recording electrodes were implanted in mice. After a 24 h baseline recording, limb ischemia was induced by tightening an elastic band around the left quadriceps for 10 minutes followed by 10 minutes of release for two cycles. Two days following remote preconditioning, a second 24 h EEG/EMG recording was completed and was immediately followed by a 60-minute suture occlusion of the middle cerebral artery (modeled ischemic stroke). This experiment was then repeated in a model of circadian and sleep abnormalities (Bmal1knockout [KO] mice sleep 2 h more than wild-type littermates). Brain infarction was determined by vital dye staining, and sleep was assessed by trained identification of EEG/EMG recordings.
  
  
  
  Two days after limb ischemia, wild-type mice slept an additional 2.4 h. This additional sleep was primarily comprised of non-rapid eye movement (NREM) sleep during the middle of the light-phase (i.e., naps). Repeating the experiment but preventing increases in sleep after limb ischemia abolished tolerance to ischemic stroke. InBmal1knockout mice, remote preconditioning did not increase daily sleep nor provide tolerance to subsequent focal ischemia.
  
  
  
  These results suggest that sleep induced by remote preconditioning is both sufficient and necessary for its neuroprotective effects on stroke outcome.
authors: Circadian Rhythms and Sleep Disorders Program, Department of Neurobiology, Morehouse School of Medicine, Atlanta GA.|Behavioral Biology Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD.
authors: Allison J
authors: AJ
authors: Brager
authors: Translational Programs in Stroke, Neuroscience Institute, Morehouse School of Medicine, Atlanta GA.
authors: Tao
authors: T
authors: Yang
authors: Circadian Rhythms and Sleep Disorders Program, Department of Neurobiology, Morehouse School of Medicine, Atlanta GA.
authors: J Christopher
authors: JC
authors: Ehlen
authors: Translational Programs in Stroke, Neuroscience Institute, Morehouse School of Medicine, Atlanta GA.
authors: Roger P
authors: RP
authors: Simon
authors: Translational Programs in Stroke, Neuroscience Institute, Morehouse School of Medicine, Atlanta GA.
authors: Robert
authors: R
authors: Meller
authors: Circadian Rhythms and Sleep Disorders Program, Department of Neurobiology, Morehouse School of Medicine, Atlanta GA.|Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA.
authors: Ketema N
authors: KN
authors: Paul
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D004569:Electroencephalography; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000066829:Neuroprotection / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000502:physiology*; D020521:Stroke / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*
keywords: circadian; homeostatic; ischemia; mouse; neuroprotection; tolerance