Abstract
In the present study, we investigated cerebral ischemia‐induced expression changes in caveolins, regulatory signaling molecules, and autophagy signaling. Cerebral ischemia was induced by middle cerebral artery occlusion (MCAo)–reperfusion in spontaneously hypertensive (SHR) rats (~200 mmHg) and normotensive Wistar Kyoto (WKY) rats. All MCAo surgery groups had neurological deficiency, motor dysfunction, and disruption of balance ability; these pathological changes were more severe in SHR rats compared with WKY rats. Additionally, the caveolin and nNOS levels were decreased in brain tissue of the MCAo group, but the iNOS and GFAP levels were increased. Moreover LC3‐II and beclin‐1 protein expression were elevated in MCAo groups. These results implicate MCAo as a strong causative factor in brain impairment at the molecular level. SHR rats had delayed functional recovery, increased iNOS and autophagic cell death, and decreased caveolin and nNOS levels compared with WKY rats. Therefore, these results suggest that forced exercise is beneficial in promoting brain damage recovery following cerebral ischemia. Finally, improved motor behavioral outcome induced by forced exercise in MCAo rats was associated with altered caveolin expression and caveolin interaction with signaling molecules in ischemic brain regions, which was related to functional rescue of neuromuscular communication.
Highlights
Cerebrovascular disease (CVD) is the third leading cause of death and long-term disability worldwide [1]
spontaneously hypertensive rats (SHR) rats with approximately 200 mmHg systolic blood pressure and age-matched WKY rats (12 weeks of age) were used as controls for middle cerebral artery occlusion (MCAo) surgery
Forced exercise diminished the inducible NOS (iNOS) mRNA level in both WKY and SHR rats (p < 0.01); despite this change, iNOS mRNA level in the SHR MCAo + Ex group was higher than that in the WKY MCAo + Ex group. These results suggest that hypertension may exacerbate iNOS expression in focal cerebral ischemia. neuronal NOS (nNOS) mRNA levels in both MCAo groups were not significantly different compared with the Sham groups
Summary
Cerebrovascular disease (CVD) is the third leading cause of death and long-term disability worldwide [1]. It is the most prevalent neurological disorder in terms of both morbidity and mortality [2]. Cerebral ischemia results from the loss of blood supply to part of the brain caused by various mechanisms such as atherothrombosis, cardioembolism, or hemodynamic compromise; and loss of brain function develops rapidly afterwards [1,2,4]. Risk factors for cerebral ischemia include advanced age, hypertension, previous stroke or transient ischemic attack (TIA), diabetes, high cholesterol, and atrial fibrillation [1,2,3,4]. Blood pressure is thought to be a significant determinant of stroke risk in both normotensive and hypertensive populations [6]
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