ABSTRACT
Obstructive sleep apnea (OSA) is associated with ischemic stroke. There is, however, a lack of knowledge on the exact cause-effect relationship, and preclinical models of OSA for experimental ischemic stroke investigations are not well characterized. In this review, we discuss sleep apnea and its relationship with stroke risk factors. We consider how OSA may lead to ischemic stroke and how OSA-induced metabolic syndrome and hypothalamic-pituitary axis (HPA) dysfunction could serve as therapeutic targets to prevent ischemic stroke. Further, we examine the translational potential of established preclinical models of OSA. We conclude that metabolic syndrome and HPA dysfunction, which are often overlooked in the context of experimental stroke and OSA studies, are crucial for experimental consideration to improve the body of knowledge as well as the translational potential of investigative efforts.
Subject(s)
Hypothalamo-Hypophyseal System , Ischemic Stroke , Sleep Apnea, Obstructive , Humans , Ischemic Stroke/physiopathology , Ischemic Stroke/complications , Animals , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/physiopathology , Hypothalamo-Hypophyseal System/physiopathology , Disease Models, Animal , Risk Factors , Translational Research, Biomedical , Metabolic Syndrome/physiopathology , Metabolic Syndrome/complications , Pituitary-Adrenal System/physiopathology , Sleep Apnea Syndromes/complications , Sleep Apnea Syndromes/physiopathologyABSTRACT
Intraluminal monofilament model of middle cerebral artery occlusion (MCAO) is widely adopted for ischemic stroke; and Sprague-Dawley (SD) rats are commonly used rodents for preclinical research. Due to the paucity of information on the appropriate monofilament size for inducing MCAO in SD rats and the importance of including middle-aged models in ischemic stroke studies, we aimed to: (i). determine an appropriate Doccol® monofilament size for middle-aged male SD rats which weighed > 500 g following 24-h transient MCAO survival as well as (ii). demonstrate the optimal Doccol® filament size for middle-aged males (≤ 500 g) and females (273-300 g) while using young adult male SD rats (372-472 g) as control for severity of infarct volume following 7-days post-MCAO. All rats were subjected to 90-min transient MCAO. We show that 0.43 mm Doccol® monofilament size is more appropriate to induce large infarct lesion and optimal functional deficit when compared to 0.45 mm and 0.47 mm at 24 h post-MCAO. Our data on infarct volumes at 7 days post-MCAO as well as the observed weight loss and functional deficits at post-MCAO days 1, 3 and 7 demonstrate that 0.41 mm, 0.37 mm and 0.39 mm are optimal Doccol® filament sizes for middle-aged male (477.3 ± 39.61 g) and female (302.6 ± 26.28 g) as well as young-adult male (362.2 ± 28.38 g) SD rats, respectively.