title: Identification of Sleep-Modulated Pathways Involved in Neuroprotection from Stroke.
abstract: OBJECTIVE
  Sleep deprivation (SDp) performed before stroke induces an ischemic tolerance state as observed in other forms of preconditioning. As the mechanisms underlying this effect are not well understood, we used DNA oligonucleotide microarray analysis to identify the genes and the gene-pathways underlying SDp preconditioning effects.
  
  
  METHODS
  Gene expression was analyzed 3 days after stroke in 4 experimental groups: (i) SDp performed before focal cerebral ischemia (IS) induction; (ii) SDp performed before sham surgery; (iii) IS without SDp; and (iv) sham surgery without SDp. SDp was performed by gentle handling during the last 6 h of the light period, and ischemia was induced immediately after.
  
  
  METHODS
  Basic sleep research laboratory.
  
  
  RESULTS
  Stroke induced a massive alteration in gene expression both in sleep deprived and non-sleep deprived animals. However, compared to animals that underwent ischemia alone, SDp induced a general reduction in transcriptional changes with a reduction in the upregulation of genes involved in cell cycle regulation and immune response. Moreover, an upregulation of a new neuroendocrine pathway which included melanin concentrating hormone, glycoprotein hormones-α-polypeptide and hypocretin was observed exclusively in rats sleep deprived before stroke.
  
  
  CONCLUSIONS
  Our data indicate that sleep deprivation before stroke reprogrammed the signaling response to injury. The inhibition of cell cycle regulation and inflammation are neuroprotective mechanisms reported also for other forms of preconditioning treatment, whereas the implication of the neuroendocrine function is novel and has never been described before. These results therefore provide new insights into neuroprotective mechanisms involved in ischemic tolerance mechanisms.
authors.affiliation: ZEN - Zentrum für Experimentelle Neurologie, Inselspital, Bern, Switzerland.|Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
authors.forename: Marta
authors.initials: M
authors.lastname: Pace
authors.affiliation: ZEN - Zentrum für Experimentelle Neurologie, Inselspital, Bern, Switzerland.
authors.forename: Francesca
authors.initials: F
authors.lastname: Baracchi
authors.affiliation: ZEN - Zentrum für Experimentelle Neurologie, Inselspital, Bern, Switzerland.
authors.forename: Bo
authors.initials: B
authors.lastname: Gao
authors.affiliation: ZEN - Zentrum für Experimentelle Neurologie, Inselspital, Bern, Switzerland.|Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
authors.forename: Claudio
authors.initials: C
authors.lastname: Bassetti
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000235:genetics / Q000503:physiopathology; D002453:Cell Cycle / Q000235:genetics; D020869:Gene Expression Profiling; D015292:Glycoprotein Hormones, alpha Subunit / Q000235:genetics; D007028:Hypothalamic Hormones / Q000235:genetics; D007109:Immunity / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000517:prevention & control; D019194:Ischemic Preconditioning; D008297:Male; D008543:Melanins / Q000235:genetics; D000066829:Neuroprotection / Q000235:genetics / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D000068797:Orexins / Q000235:genetics; D010907:Pituitary Hormones / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000235:genetics; D012890:Sleep / Q000235:genetics / Q000502:physiology; D012892:Sleep Deprivation / Q000235:genetics / Q000503:physiopathology*; D020521:Stroke / Q000235:genetics / Q000503:physiopathology* / Q000517:prevention & control* / Q000601:surgery; D015854:Up-Regulation / Q000235:genetics
chemical_list: D015292:Glycoprotein Hormones, alpha Subunit; D007028:Hypothalamic Hormones; D008543:Melanins; D000068797:Orexins; D010907:Pituitary Hormones; C019463:melanin-concentrating hormone
keywords: neuroprotection; preconditioning; sleep deprivation; stroke