Slow-wave sleep and REM sleep without atonia predict motor progression in Parkinson's disease.

BACKGROUND: Growing evidence supports the potential role of sleep in the motor progression of Parkinson's disease (PD). Slow-wave sleep (SWS) and rapid eye movement (REM) sleep without atonia (RWA) are important sleep parameters. The association between SWS and RWA with PD motor progression and their predictive value have not yet been elucidated. METHODS: We retro-prospectively analyzed clinical and polysomnographic data of 136 patients with PD. The motor symptoms were assessed using Unified Parkinson's Disease Rating Scale Part III (UPDRS III) at baseline and follow-up to determine its progression. Partial correlation analysis was used to explore the cross-sectional associations between slow-wave energy (SWE), RWA and clinical symptoms. Longitudinal analyses were performed using Cox regression and linear mixed-effects models. RESULTS: Among 136 PD participants, cross-sectional partial correlation analysis showed SWE decreased with the prolongation of the disease course (P = 0.046), RWA density was positively correlated with Hoehn & Yahr (H-Y) stage (tonic RWA, P < 0.001; phasic RWA, P = 0.002). Cox regression analysis confirmed that low SWE (HR = 1.739, 95% CI = 1.038-2.914; P = 0.036; FDR-P = 0.036) and high tonic RWA (HR = 0.575, 95% CI = 0.343-0.963; P = 0.032; FDR-P = 0.036) were predictors of motor symptom progression. Furthermore, we found that lower SWE predicted faster rate of axial motor progression (P < 0.001; FDR-P < 0.001) while higher tonic RWA density was associated with faster rate of rigidity progression (P = 0.006; FDR-P = 0.024) using linear mixed-effects models. CONCLUSIONS: These findings suggest that SWS and RWA might represent markers of different motor subtypes progression in PD.

Involvement of angiotensin-(1-7) in the neuroprotection of captopril against focal cerebral ischemia.

Accumulating evidence suggests that brain angiotensin-converting enzyme (ACE)/angiotensin II/angiotensin II type I receptor axis is activated and thus contributes to the neuronal injury during ischemic stroke. Conversely, inhibition of this axis using centrally active ACE inhibitor captopril was proven neuroprotective in rodents with focal cerebral ischemia. Interestingly, captopril was able to increase angiotensin-(1-7) [Ang-(1-7)] levels in the peripheral organs. As the main component of the alternative renin-angiotensin system axis in the brain, Ang-(1-7) was revealed to protect against focal cerebral ischemia via a MAS1 receptor-dependent manner. Based on this evidence, we hypothesized that Ang-(1-7) might contribute to the neuroprotection of captopril during ischemic stroke. In this study, we evaluated this hypothesis using a rat model of focal cerebral ischemia. We revealed that brain ACE2 activity and Ang-(1-7) levels were significantly elevated following captopril treatment in rats with focal cerebral ischemia. More importantly, we showed that the neuroprotection provided by captopril was partially reversed by A-779, an antagonist for Ang-(1-7) receptor MAS1, indicating that Ang-(1-7) was involved in the neuroprotection of captopril. These findings have uncovered new mechanisms by which captopril protects against focal cerebral ischemia and further suggest that captopril may have practical clinical use for stroke prevention and treatment in addition to its antihypertensive effect.

Up-regulation of angiotensin-converting enzyme in response to acute ischemic stroke via ERK/NF-κB pathway in spontaneously hypertensive rats.

Cerebral ischemic stroke is usually caused by a temporary or permanent decrease in blood supply to the brain. Despite general progress in diagnosis and treatment, the prognosis of stroke is still unsatisfactory, and more detailed potential mechanisms are needed to investigate underlying the pathological process. Here, we showed that serum angiotensin-converting enzyme (ACE) concentration was positively correlated with infarct volume after acute ischemic stroke (AIS). Moreover, using a permanent middle cerebral artery occlusion rat model, we indicated for the first time that increased ACE expression in response to AIS was regulated by the ERK/NF-κB pathway in peri-infarct regions. More importantly, we disclosed that angiotensin II type 1 receptors were implicated in up-regulation of ACE expression in peri-infarct regions. These findings offer insight into ACE expression and activity in response to stroke, and further our understanding of ACE mechanisms.