Sleep disturbance impairs stroke recovery in the rat.

STUDY OBJECTIVES There is a lack of experimental evidence to support the hypothesis that sleep may modulate stroke outcome as suggested by clinical observations. We have previously shown that sleep disturbance (SDis) over 3 days aggravates brain damage in a rat model of focal cerebral ischemia. The aim of this study is to further investigate effects of SDis on long-term stroke recovery and neuroplasticity as assessed by axonal sprouting, neurogenesis, and angiogenesis. DESIGN Focal cerebral ischemia was induced by permanent occlusion of the distal branches of middle cerebral artery. Twelve hours after initiation of ischemia, SDis was performed over 3 consecutive days (deprivation of 80% sleep during the 12-h light phase). Weekly assessments on sensorimotor function by the single pellet reaching test (SPR) were performed for 5 weeks after surgery. Axonal sprouting was evaluated by anterograde tracing with biotinylated dextran amine (BDA) and neurogenesis/angiogenesis by bromodeoxyuridine (BrdU) labelling along with cell-type markers. Control groups included ischemia without SDis, sham with SDis, and sham without SDis. SETTING Basic sleep research laboratory. MEASUREMENTS AND RESULTS Rats subjected to SDis after ischemia showed significantly less recovery of forearm motor skills during the post-stroke period of 5 weeks. This effect was accompanied by a substantial reduction in axonal sprouting, expression of synaptophysin, and the ischemia-stimulated neural and vascular cell proliferation. CONCLUSION SDis has detrimental effects on functional and morphological/structural outcomes after stroke, suggesting a role of sleep in the modulation of recovery processes and neuroplasticity.

[1]  J. Sarnthein,et al.  Sleep disruption aggravates focal cerebral ischemia in the rat. , 2010, Sleep.

[2]  L. Zagrean,et al.  Sleep deprivation attenuates experimental stroke severity in rats , 2010, Experimental Neurology.

[3]  S. Carmichael.  Translating the frontiers of brain repair to treatments: Starting not to break the rules , 2010, Neurobiology of Disease.

[4]  Claudio L Bassetti,et al.  Sleep-related breathing and sleep-wake disturbances in ischemic stroke , 2009, Neurology.

[5]  M. Zhuo,et al.  Sleep deprivation impairs cAMP signaling in the hippocampus , 2009, Nature.

[6]  G. Norman,et al.  Sleep deprivation attenuates inflammatory responses and ischemic cell death , 2009, Experimental Neurology.

[7]  C. Verfaillie,et al.  Stem cells for ischemic brain injury: A critical review , 2009, The Journal of comparative neurology.

[8]  Peter Meerlo,et al.  New neurons in the adult brain: the role of sleep and consequences of sleep loss. , 2009, Sleep medicine reviews.

[9]  A. Lüthi,et al.  Consequences of sleep deprivation on neurotransmitter receptor expression and function , 2009, The European journal of neuroscience.

[10]  Derk-Jan Dijk,et al.  Sleep function: current questions and new approaches , 2009, The European journal of neuroscience.

[11]  M. Chopp,et al.  Neurorestorative therapies for stroke: underlying mechanisms and translation to the clinic , 2009, The Lancet Neurology.

[12]  M. Chopp,et al.  Mechanisms underlying improved recovery of neurological function after stroke in the rodent after treatment with neurorestorative cell-based therapies. , 2009, Stroke.

[13]  M. Walker.  The Role of Sleep in Cognition and Emotion , 2009, Annals of the New York Academy of Sciences.

[14]  G. Tononi,et al.  Long-Term Homeostasis of Extracellular Glutamate in the Rat Cerebral Cortex across Sleep and Waking States , 2009, The Journal of Neuroscience.

[15]  Karl H. Plate,et al.  Angiogenesis after cerebral ischemia , 2009, Acta Neuropathologica.

[16]  Veronica Guillen,et al.  Motor Recovery and Axonal Plasticity With Short-Term Amphetamine After Stroke , 2009, Stroke.

[17]  M. Chopp,et al.  Down‐regulation of neurocan expression in reactive astrocytes promotes axonal regeneration and facilitates the neurorestorative effects of bone marrow stromal cells in the ischemic rat brain , 2008, Glia.

[18]  I. Whishaw,et al.  The problem of relating plasticity and skilled reaching after motor cortex stroke in the rat , 2008, Behavioural Brain Research.

[19]  C. Baumann,et al.  Gamma-Hydroxybutyrate Accelerates Functional Recovery after Focal Cerebral Ischemia , 2008, Cerebrovascular Diseases.

[20]  Steven C Cramer,et al.  Repairing the human brain after stroke. II. Restorative therapies , 2008, Annals of neurology.

[21]  J. Epp,et al.  Sleep deprivation can inhibit adult hippocampal neurogenesis independent of adrenal stress hormones. , 2008, American journal of physiology. Regulatory, integrative and comparative physiology.

[22]  S. Carmichael,et al.  Themes and Strategies for Studying the Biology of Stroke Recovery in the Poststroke Epoch , 2008, Stroke.

[23]  Steven C. Cramer.  Repairing the human brain after stroke: I. Mechanisms of spontaneous recovery , 2008, Annals of neurology.

[24]  S. Paek,et al.  Endogenous neurogenesis and neovascularization in the neocortex of the rat after focal cerebral ischemia , 2008, Journal of neuroscience research.

[25]  C. Bassetti,et al.  Correlation between sleep EEG and cognitive functions after hemispheric ischemic stroke , 2008, Clinical Neurophysiology.

[26]  R. Dempsey,et al.  Repairing brain after stroke: A review on post-ischemic neurogenesis , 2007, Neurochemistry International.

[27]  E. Gould,et al.  Sleep deprivation inhibits adult neurogenesis in the hippocampus by elevating glucocorticoids , 2006, Proceedings of the National Academy of Sciences.

[28]  M. Tafti,et al.  Sleep EEG changes after middle cerebral artery infarcts in mice: different effects of striatal and cortical lesions. , 2006, Sleep.

[29]  G. Kartje,et al.  Axonal plasticity is associated with motor recovery following amphetamine treatment combined with rehabilitation after brain injury in the adult rat , 2006, Brain Research.

[30]  S. Carmichael.  Cellular and molecular mechanisms of neural repair after stroke: Making waves , 2006, Annals of neurology.

[31]  J. Parent,et al.  Adult Neurogenesis and the Ischemic Forebrain , 2006, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[32]  T. Hagg.  Molecular regulation of adult CNS neurogenesis: an integrated view , 2005, Trends in Neurosciences.

[33]  S. Carmichael,et al.  Growth-associated gene expression after stroke: evidence for a growth-promoting region in peri-infarct cortex , 2005, Experimental Neurology.

[34]  H. Cameron,et al.  New GABAergic interneurons in the adult neocortex and striatum are generated from different precursors , 2005, The Journal of cell biology.

[35]  I. Whishaw,et al.  Skilled reaching impairments from the lateral frontal cortex component of middle cerebral artery stroke: a qualitative and quantitative comparison to focal motor cortex lesions in rats , 2005, Behavioural Brain Research.

[36]  Jidong Fang,et al.  Sleep deprivation impairs spatial memory and decreases extracellular signal-regulated kinase phosphorylation in the hippocampus , 2004, Brain Research.

[37]  S. Davies,et al.  Decorin suppresses neurocan, brevican, phosphacan and NG2 expression and promotes axon growth across adult rat spinal cord injuries , 2004, The European journal of neuroscience.

[38]  Jeffrey C Magee,et al.  Sleep Deprivation Causes Behavioral, Synaptic, and Membrane Excitability Alterations in Hippocampal Neurons , 2003, The Journal of Neuroscience.

[39]  E. Ling,et al.  Sleep Deprivation Inhibits Expression of NADPH-d and NOS while Activating Microglia and Astroglia in the Rat Hippocampus , 2003, Cells Tissues Organs.

[40]  T. Erkinjuntti,et al.  Insomnia in Ischemic Stroke Patients , 2002, Cerebrovascular Diseases.

[41]  M. Chesselet,et al.  Synchronous Neuronal Activity Is a Signal for Axonal Sprouting after Cortical Lesions in the Adult , 2002, The Journal of Neuroscience.

[42]  A. Reiner,et al.  Pathway tracing using biotinylated dextran amines , 2000, Journal of Neuroscience Methods.

[43]  R. P. Stroemer,et al.  Enhanced neocortical neural sprouting, synaptogenesis, and behavioral recovery with D-amphetamine therapy after neocortical infarction in rats. , 1998, Stroke.

[44]  E. van Cauter,et al.  Simultaneous stimulation of slow-wave sleep and growth hormone secretion by gamma-hydroxybutyrate in normal young Men. , 1997, The Journal of clinical investigation.

[45]  M F Chesselet,et al.  Anatomical and functional evidence for lesion‐specific sprouting of corticostriatal input in the adult rat , 1996, The Journal of comparative neurology.

[46]  E. Hogan,et al.  A model of focal ischemic stroke in the rat: reproducible extensive cortical infarction. , 1986, Stroke.

[47]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .