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Short‐term exposure to chronic intermittent hypoxia (CIH) to model repetitive hypoxemias of sleep apnea is sufficient to confer protection from brain ischemia
Author(s) -
Toney Glenn M.,
Wellford Alexander J.,
Andrade Mary Ann
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1010.11
Subject(s) - medicine , ischemia , anesthesia , intermittent hypoxia , neuroprotection , hypoxia (environmental) , stroke (engine) , hypoxemia , cardiology , apnea , obstructive sleep apnea , oxygen , mechanical engineering , chemistry , organic chemistry , engineering
Sleep Apnea (SA), a form of sleep disordered breathing, is characterized by repetitive episodes of arterial hypoxemia resulting from interrupted breathing. Often SA results in develop of hypertension, which studies demonstrate results from increased vasoconstriction driven by excessive sympathetic nerve activity. The sympathetic activation response involves recruitment of pre‐sympathetic neurons in the hypothalamic paraventricular nucleus (PVN). Clinical studies report that SA increases the risk of stroke by ~4‐fold. By contrast, pre‐clinical studies in mice suggest that prolonged (~30 days) exposure to CIH is neuroprotective in the middle cerebral artery occlusion (MCAO) model of stroke. Thus available data suggest that neural, glial and/or vascular adaptations to repetitive hypoxia confer protection from brain ischemia. To gain insight into mechanisms of CIH‐induced ischemic protection, effects of short‐term (7 days) exposure to moderate CIH (21% to 10% O2, 10 episodes/h, 8 h/day) on brain tissue infarct volumes were quantified. This was accomplish using a permanent MCAO model as well as a photothrombic lesioning (PTL) model of focal ischemic injury. Results indicate that exposure to CIH for just 7 days reduced the estimated volume of MCAO‐ and hypothalamic PTL‐induced focal ischemic infarcts. In the MCAO model, CIH reduced infarct volume by 31 ± 4 % (SEM, n=5) relative to normoxic controls. CIH more effectively reduced infarct volume in the hypothalamic PTL model by 65 ± 9 % (SEM, n=7). These findings indicate that CIH exposure for only 7 days is sufficient to induce robust protective adaptations. PO2 recordings from multiple brain regions indicate that episodes of CIH cause rapid reductions of tissue O2 availability. However, episodes of brain tissue hypoxia showed little change over consecutive days of CIH exposure, suggesting that CIH does not induce progressive cerebrovascular adaptations that protect brain tissue from experiencing acute hypoxia. Thus findings suggest that adaptations among resident neurons and/or glia promote tissue survival in the face of focal ischemia. Support or Funding Information Support: NIH HL088052 & AHA 15GRNT25710176 (GMT)