Identification of Sleep-Modulated Pathways Involved in Neuroprotection from Stroke.

Pace, Marta; Baracchi, Francesca; Gao, Bo; Bassetti, Claudio (2015). Identification of Sleep-Modulated Pathways Involved in Neuroprotection from Stroke. Sleep, 38(11), pp. 1707-1718. American Academy of Sleep Medicine

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STUDY OBJECTIVES 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. DESIGN 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. SETTINGS Basic sleep research laboratory. MEASUREMENTS AND 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. CONCLUSION 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.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology

UniBE Contributor:

Pace, Marta; Baracchi, Francesca; Gao, Bo and Bassetti, Claudio


600 Technology > 610 Medicine & health




American Academy of Sleep Medicine




Valentina Rossetti

Date Deposited:

30 Sep 2015 15:17

Last Modified:

28 Nov 2015 01:30

PubMed ID:


Uncontrolled Keywords:

Stroke; neuroprotection; preconditioning; sleep deprivation


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