Abstract 46: Obstructive Sleep Apnea (OSA) Accelerates Cerebral Pathology in Spontaneously Hypertensive Stroke Prone Rat (SHRsp)
Cerebral small vessel disease (CSVD) and its pathological changes in small vessels in brain, is responsible for lacunar infarcts, white matter lesions, hemorrhages, microbleeds, and cognitive impairment. Although it has been suggested that OSA has a role in CSVD, there are no controlled studies relating OSA to CSVD and it pathological consequences. We tested the hypothesis that OSA in SHRsp rats, a model for CSVD, accelerates the development of associated brain pathologies. Chronic intermittent airway obstructions (termed OSA, 10 sec in duration, 60/hr, during 8 hr of the sleep cycle) were induced by remotely inflating balloons implanted in the tracheas of SHRsp and their parent strain, Wistar Kyoto rats (WKY). Studies were conducted at 12 and 20 weeks of age after being subjected to 14 days of OSA. Sham rats had balloons implanted but without inflations to occlude the airway. Systolic blood pressure was significantly increased in SHRsp with OSA by 58 ± 15 and 32 ± 7 mm Hg at 12 and 20 weeks respectively compared to SHRsp sham rats (n=7-10, p<0.05). Working memory as assessed by novel object recognition was impaired in the SHRsp with OSA at both 12 and 20 weeks (n=6, p<0.01). IgG extravasation, a measure of blood brain barrier integrity, was significantly increased (n=6, p<0.05) in small vessels of the 12 and 20 week SHRsp OSA groups. In the 12 week SHRsp OSA group the IgG extravasation was mainly present in the white matter small vessels, while in the 20 week SHRsp OSA group, which contained far greater (p<0.05, n=6) IgG positive small vessels, the majority of the IgG extravasation was found in the grey matter. Activation of microglia in the external capsule (as determined by morphometric analysis) was significantly greater in the SHRsp OSA group compared to all other groups of rats (n=6 each group, p<0.05). There was a significant loss of white matter as indicated by a 192 ± 10% increase (n=6, p<0.05) in the breakdown products of myelin basic protein in the SHRsp OSA group at 20 weeks but not at 12 weeks. We conclude that OSA in the SHRsp accelerates the onset of the cerebral pathologies associated with cerebral small vessel disease.
Author Disclosures: E.E. Lloyd: None. D.J. Durgan: None. S.C. Phillips: None. R.M. Bryan Jr.: None.
- © 2015 by American Heart Association, Inc.