Background and Purpose- We aimed to examine the relation of baseline plasma zinc with the risk of first stroke and investigate any possible effect modifiers in hypertensive patients. Methods- The study population was drawn from the CSPPT (China Stroke Primary Prevention Trial), using a nested case-control design, including 599 first stroke cases and 599 matched controls. Results- Compared with participants with baseline plasma zinc <106.9 mu g/dL (median), a significantly lower risk of first hemorrhagic stroke was found in those with plasma zinc >= 106.9 mu g/dL (multivariate-adjusted odds ratio, 0.45; 95% CI, 0.21-0.94). Furthermore, the inverse plasma zinc-first hemorrhagic stroke association was significantly stronger in participants with body mass index >= 25.0 kg/m(2) or plasma copper <100.1 mu g/dL at baseline (P-interaction <0.05 for both variables). However, there was no significant association between plasma zinc and first ischemic stroke (<103.3 versus >= 103.3 mu g/dL [median]; multivariate-adjusted odds ratio, 1.16; 95% CI, 0.83-1.61). Conclusions- In this sample of hypertensive patients, we found a significant, inverse association between plasma zinc and first hemorrhagic stroke.
Background and Purpose- Accumulating evidence has demonstrated hemodynamic abnormalities and cerebral hypoperfusion in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Increased venous susceptibility assessed by susceptibility weighted imaging and mapping has been shown to indicate a decrease in venous oxygen saturation. This study aimed to investigate whether altered venous oxygen saturation is related to clinical phenotypes of CADASIL patients. Methods- Using 7.0-T susceptibility weighted imaging and mapping, we compared venous susceptibility of cortical veins between 41 CADASIL patients and 43 age- and sex-matched healthy controls. The magnetic resonance imaging lesion load, mini-mental state examination score, Barthel Index, and modified Rankin Scale were examined in the patient group, and the correlations between venous susceptibility and clinical characteristics were analyzed. Results- Venous susceptibility increased with age (r=0.508, P=0.001) and was higher in CADASIL patients than in healthy controls (t=-4.673; P<0.001). We found a positive association between venous susceptibility and the age-related white matter change scores (r=0.364; P=0.019), number of lacunar infarctions (r=0.520; P<0.001), number of cerebral microbleeds (rho=0.445; P=0.004), and small-vessel disease scores (rho=0.465; P=0.002) in CADASIL patients. Moreover, increased venous susceptibility was associated with higher modified Rankin Scale scores in CADASIL patients after adjustment for age- and small-vessel disease scores (odds ratio=3.178; 95% CI, 1.101-9.179; P=0.033). Conclusions- Our findings indicate that extensive cerebral hypoperfusion may induce central nervous system impairment in CADASIL, and susceptibility weighted imaging and mapping could be used clinically to assess the condition of CADASIL patients.
Background and Purpose- We aimed to systematically investigate the characteristics of cervicocranial artery dissection (CCAD) on high-resolution magnetic resonance imaging that are associated with acute ischemic stroke. Methods- Patients with CCAD were recruited and divided into stroke and nonstroke groups. The lesion location, the presence of a double lumen, intimal flap, intramural hematoma, pseudoaneurysm, irregular surface, intraluminal thrombus, and other quantitative parameters of each dissected segment were reviewed. Multiple logistic regression was used to examine the association between imaging features of CCAD and ischemic stroke. Results- A total of 145 affected vessels from 118 patients with CCAD were analyzed. Anterior circulation, intramural hematoma, irregular surface, intraluminal thrombus, and severe stenosis (>70%) on high-resolution magnetic resonance imaging were more prevalent in CCAD patient with stroke (54.4% versus 36.4%; P=0.030, 96.2% versus 84.8%; P=0.017, 74.7% versus 37.9%; P<0.001, 44.3% versus 4.5%; P<0.001, and 54.4% versus 31.8%; P=0.008, respectively). In multivariable logistic regression analysis, the presence of irregular surface and intraluminal thrombus on imaging were independently associated with acute ischemic stroke in CCAD with odds ratios of 4.29 (95% CI, 1.61-11.46, P=0.004) and 7.48 (95% CI, 1.64-34.07, P=0.009). Conclusions- The current findings supported that the presence of irregular surface and intraluminal thrombus were related to stroke occurrence in patients with CCAD. High-resolution magnetic resonance imaging might give insights into pathogenesis of ischemic stroke in CCAD. It may be useful for individual prediction of ischemic stroke early in CCAD.
Background and Purpose RACK1 (receptor for activated protein kinase C 1) is an integral component of ribosomes with neuroprotective functions. The goal of this study was to determine the role of RACK1 in cerebral ischemia-reperfusion (I/R) injury and the underlying mechanisms. Methods A middle cerebral artery occlusion/reperfusion model in adult male Sprague Dawley rats (250-280 g) was established, and cultured neurons were exposed to oxygen-glucose deprivation/reoxygenation to mimic I/R injury in vitro. Expression vectors encoding wild-type RACK1 and RACK1 with T50A mutation (T50A) were constructed and administered to rats by intracerebroventricular injection. Results The potential role of RACK1 in cerebral I/R injury was confirmed by the decreased protein levels of RACK1 within penumbra tissue, especially of neurons. Second, there was an increase in the phosphorylation ratio of RACK1 at the threonine/serine residues at 1.5 hours after middle cerebral artery occlusion onset. Third, based on site-specific mutagenesis, we identified T50 as a key site for RACK1 phosphorylation during I/R. Fourth, wild-type RACK1 overexpression reduced infarct size, neuronal death, neuronal tissue loss, and neurobehavioral dysfunction, while RACK1 (T50A) overexpression exerted opposite effects. Finally, we found that RACK1 phosphorylation at T50 induced a loss of ribosomal RACK1, which switched RACK1 from beclin-1 translation inhibition to autophagy induction following I/R. Conclusions RACK1 phosphorylation may be a potential intervention target for neurons during I/R; thus, exogenous supplementation of RACK1 may be a novel approach for ameliorating I/R injury.
Background and Purpose Research has shown that balance training is effective for reducing the fear of falling in individuals with a history of stroke. In this study, we evaluated (1) whether cognitive behavior therapy could augment the beneficial effects of task-oriented balance training (TOBT) in reducing the fear of falling in chronic stroke survivors and (2) whether it could, in turn, reduce fear-avoidance behavior and improve related health outcomes. Methods Eighty-nine cognitively intact subjects with mildly impaired balance ability were randomized into the following 2 groups that underwent 90-minutes interventions 2 days per week for 8 weeks: (1) cognitive behavior therapy + TOBT or (2) general health education + TOBT (control). The primary outcome was the fear of falling, and the secondary outcomes were fear-avoidance behavior, balance, fall risk, independent daily living, community integration, and health-related quality of life. The outcomes were assessed at baseline, after 4 and 8 weeks of intervention, and 3 and 12 months after completing the intervention. Results Eighty-two subjects completed the intervention and follow-up assessments. From postintervention to 12 months after completing the intervention, the cognitive behavior therapy + TOBT participants reported greater reduction in the fear of falling and fear-avoidance behavior and greater improvements in balance and independent daily living than the general health education + TOBT participants. Conclusions Cognitive behavior therapy should be considered as an adjuvant therapy to standard physiotherapy for cognitively intact individuals with a history of stroke. Clinical Trial Registration URL: https://clinicaltrials.gov. Unique identifier: NCT02937532.
Background and Purpose CLEC-2 (C-type lectin-like receptor 2) is a C-type lectin receptor highly expressed on platelets with the prominent involvement in platelet activation, which was increased in coronary heart disease. Given the role of platelet activation in ischemic stroke and the connections between coronary heart disease and ischemic stroke, CLEC-2 might be a candidate marker of ischemic stroke. Here, we aimed to examine the prognostic significance of CLEC-2 in patients with acute ischemic stroke (AIS). Methods Three hundred fifty-two patients with AIS within 7 days and 112 healthy controls were prospectively studied. Plasma CLEC-2 (pCLEC-2) and some conventional risk factors of stroke were examined. Stroke progression was defined as any new neurological symptoms/signs or any neurological worsening within 7 days after stroke onset, and poor prognosis was defined as modified Rankin Scale scores >2 at 90 days. The association between pCLEC-2 and stroke progression/prognosis was evaluated using regression models. Results Patients with AIS had a significantly higher level of pCLEC-2 than that of healthy controls (P<0.05). Patients with AIS with progressive stroke or poor prognosis had a much higher level of pCLEC-2 compared with those with stable stroke or good prognosis (all P<0.05). Increasing pCLEC-2 was significantly associated with an increased risk of stroke progression (odds ratio, 1.97; 95% CI, 1.11-3.50; P=0.021) and poor prognosis (odds ratio, 1.70; 95% CI, 1.17-2.48; P=0.006). Patients with the highest pCLEC-2 level were 7- to 8-fold more likely to have stroke progression compared with the lowest quartile (odds ratio, 7.69; 95% CI, 1.43-41.41). Patients with the highest pCLEC-2 level were also more likely to have poor prognosis at 90 days (odds ratio, 5.58; 95% CI, 1.76-17.68). The optimal cutoff points of pCLEC-2 for predicting stroke progression and poor prognosis were 235.48 and 207.08 pg/mL, respectively. Conclusions Increased pCLEC-2 was associated with stroke progression and poor prognosis at 90 days significantly, which indicates the prognostic role of pCLEC-2 in AIS. However, it needs to be confirmed in large-scale studies.
Background and Purpose Subarachnoid hemorrhage (SAH) has a high case fatality rate and young mean age at onset compared with other types of stroke, but the pathogenesis of SAH is not fully understood. We examined associations of systolic and diastolic blood pressure with incident nontraumatic SAH in a large prospective study in China. Methods In 2004 to 2008, 512891 adults (59% women) from the general population were recruited into the CKB study (China Kadoorie Biobank). Participants were interviewed, measured, and followed up for fatal and nonfatal events. After excluding those with prior vascular disease, Cox regression analysis was used to relate blood pressure to incident SAH events. Analyses were adjusted for major confounders and corrected for regression dilution to give associations with long-term average blood pressure. Results At baseline, mean age was 51 (SD, 11) years, and mean systolic blood pressure/diastolic blood pressure was 130.6/77.6 (SD, 21.0/11.1) mmHg. During 3.5 million person-years of follow-up, there were 553 incident SAH cases (mean age at event, 61 [SD, 11] years), yielding an overall annual incidence rate of 12.9 per 100000. Higher average levels of blood pressure were linearly and positively associated with higher risks of incident SAH: a 10 mmHg higher systolic blood pressure and a 5 mmHg higher diastolic blood pressure were associated with hazard ratios for SAH of 1.21 (95% CI, 1.13-1.29) and 1.20 (95% CI, 1.12-1.28), respectively. There was no evidence that the hazard ratios varied by age or sex or by levels of other vascular risk factors. Elevated blood pressure (systolic blood pressure, >120 mmHg) accounted for 23% of all SAH cases. Conclusions The incidence of SAH in China was comparable with estimates from Western populations. Higher levels of blood pressure were positively associated with higher risks of SAH, and elevated blood pressure accounted for about a quarter of all SAH cases.