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Pathological effects of obstructive apneas during the sleep cycle in an animal model of cerebral small vessel disease.

ABSTRACT: We tested the hypothesis that apneas during the sleep cycle exacerbate hypertension and accelerate changes that occur with cerebral small vessel disease. Obstructive sleep apnea was modeled by intermittent inflations of a chronically implanted tracheal balloon to occlude the airway during the sleep cycle (termed OSA) in spontaneously hypertensive stroke-prone (SHRSP) rats, a model of cerebral small vessel disease. SHRSP rats and their parent strain, Wistar Kyoto (WKY) rats, were exposed to OSA for 2 weeks (from 9 to 11 or from 18 to 20 weeks). At 9 weeks, hypertension was developing in the SHRSP rats and was firmly established by 18 weeks. OSA exposure increased systolic blood pressure in SHRSP rats by ?30 mm Hg in both age groups compared with shams that were surgically prepared but not exposed to OSA (P<0.05). OSA exposure also increased systolic blood pressure in WKY rats by 20 and 37 mm Hg at 11 and 20 weeks, respectively (P<0.05). OSA exposure in SHRSP rats compromised blood-brain barrier integrity in white matter at both 11 and 20 weeks of age when compared with SHRSP sham rats (P<0.05). Microglia were activated in SHRSP rats exposed to OSA but not in sham rats at 11 weeks (P<0.05). At 20 weeks, microglia were activated in sham SHRSP rats (P<0.05) compared with WKY sham rats and were not further activated by OSA. Neither was blood-brain barrier integrity altered nor microglia activated in any of the WKY groups. We conclude that OSA accelerates the onset of the cerebral pathologies associated with cerebral small vessel disease in SHRSP, but not WKY, rats.

SUBMITTER: Lloyd EE

PROVIDER: S-EPMC4567494 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Pathological effects of obstructive apneas during the sleep cycle in an animal model of cerebral small vessel disease.

Lloyd Eric E EE Durgan David J DJ Martini Sharyl R SR Bryan Robert M RM

Hypertension (Dallas, Tex. : 1979) 20150810 4

We tested the hypothesis that apneas during the sleep cycle exacerbate hypertension and accelerate changes that occur with cerebral small vessel disease. Obstructive sleep apnea was modeled by intermittent inflations of a chronically implanted tracheal balloon to occlude the airway during the sleep cycle (termed OSA) in spontaneously hypertensive stroke-prone (SHRSP) rats, a model of cerebral small vessel disease. SHRSP rats and their parent strain, Wistar Kyoto (WKY) rats, were exposed to OSA f ...[more]

PMID: 26259594

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Project description:BACKGROUND:Sleep apnea is a respiratory disorder characterized by an intermittent reduction (hypopnea) or cessation (apnea) of breathing during sleep. Depending on the presence of a breathing effort, sleep apnea is divided into obstructive sleep apnea (OSA) and central sleep apnea (CSA) based on the different pathologies involved. If the majority of apneas in a person are obstructive, they will be diagnosed as OSA or otherwise as CSA. In addition, as it is challenging and highly controversial to divide hypopneas into central or obstructive, the decision about sleep apnea type (OSA vs CSA) is made based on apneas only. Choosing the appropriate treatment relies on distinguishing between obstructive apnea (OA) and central apnea (CA). OBJECTIVE:The objective of this study was to develop a noncontact method to distinguish between OAs and CAs. METHODS:Five different computer vision-based algorithms were used to process infrared (IR) video data to track and analyze body movements to differentiate different types of apnea (OA vs CA). In the first two methods, supervised classifiers were trained to process optical flow information. In the remaining three methods, a convolutional neural network (CNN) was designed to extract distinctive features from optical flow and to distinguish OA from CA. RESULTS:Overnight sleeping data of 42 participants (mean age 53, SD 15 years; mean BMI 30, SD 7 kg/m2; 27 men and 15 women; mean number of OA 16, SD 30; mean number of CA 3, SD 7; mean apnea-hypopnea index 27, SD 31 events/hour; mean sleep duration 5 hours, SD 1 hour) were collected for this study. The test and train data were recorded in two separate laboratory rooms. The best-performing model (3D-CNN) obtained 95% accuracy and an F1 score of 89% in differentiating OA vs CA. CONCLUSIONS:In this study, the first vision-based method was developed that differentiates apnea types (OA vs CA). The developed algorithm tracks and analyses chest and abdominal movements captured via an IR video camera. Unlike previously developed approaches, this method does not require any attachment to a user that could potentially alter the sleeping condition.

Project description:Background and purposePrevious neuroimaging studies have demonstrated type 2 diabetes (T2D)-related brain structural and functional changes are partly associated with cognitive decline. However, less is known about the underlying mechanisms. Chronic hyperglycemia and microvascular complications are the two of most important risk factors related to cognitive decline in diabetes. Cerebral small vessel diseases (CSVDs), such as those defined by lacunar infarcts, white matter hyperintensities (WMHs) and microhemorrhages, are also associated with an increased risk of cognitive decline and dementia. In this study, we examined brain magnetic resonance imaging (MRI) changes in patients in the early stages of T2D without CSVDs to focus on glucose metabolism factors and to avoid the interference of vascular risk factors on T2D-related brain damage.MethodsT2D patients with disease durations of less than 5 years and without any signs of CSVDs (n = 34) were compared with healthy control subjects (n = 24). Whole-brain region-based functional connectivity was analyzed with network-based statistics (NBS), and brain surface morphology was examined. In addition, the Montreal Cognitive Assessment (MoCA) was conducted for all subjects.ResultsAt the whole-brain region-based functional connectivity level, thirty-three functional connectivities were changed in T2D patients relative to those in controls, mostly manifested as pathological between-network positive connectivity and located mainly between the sensory-motor network and auditory network. Some of the connectivities were positively correlated with blood glucose level, insulin resistance, and MoCA scores in the T2D group. The network-level analysis showed between-network hyperconnectivity in T2D patients, but no significant changes in within-network connectivity. In addition, there were no significant differences in MoCA scores or brain morphology measures, including cortical thickness, surface area, mean curvature, and gray/white matter volume, between the two groups.ConclusionThe findings indicate that pathological between-network positive connectivity occurs in the early stages of T2D without CSVDs. The abnormal connectivity may indicate that the original balance of mutual antagonistic/cooperative relationships between the networks is broken, which may be a neuroimaging basis for predicting cognitive decline in early T2D patients.

Dataset Information

Pathological effects of obstructive apneas during the sleep cycle in an animal model of cerebral small vessel disease.

Publications

Pathological effects of obstructive apneas during the sleep cycle in an animal model of cerebral small vessel disease.

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