Farrerol attenuates MPP+ -induced inflammatory response by TLR4 signaling in a microglia cell line.

Farrerol was found to possess neuroprotective effect; however, the mechanism remains unknown. The aim of the present study was to explore the effect of farrerol on MPP+ -induced inflammation in mouse microglial BV-2 cells and to elaborate the underlying mechanism. MTT assay was performed to measure the cell viability. The pro-inflammatory mediators and cytokines including interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α (TNF-α); inducible nitric oxide synthase; and cyclooxygenase 2 were measured. The expression of p-p65, p-IκBα, toll-like receptor 4 (TLR4), and myeloid differentiation primary response 88 were analyzed by western blot. We found that farrerol treatment improved cell viability in MPP+ -induced BV-2 cells. MPP+ -induced upregulation of IL-6, IL-1ß, and TNF-α was inhibited by farrerol treatment. Farrerol treatment also attenuated MPP+ -induced expression of inducible nitric oxide synthase and cyclooxygenase 2 as well as the activation of NF-κB in BV-2 cells. MPP+ -induced TLR4 signaling was markedly diminished by farrerol treatment. Knockdown of TLR4 attenuated MPP+ -induced inflammatory response in BV-2 cells. In conclusion, farrerol treatment attenuated MPP+ -induced inflammatory response by inhibiting the TLR4 signaling pathway in BV-2 cells. The results indicated that farrerol could be used as a therapeutic agent for preventing or alleviating the neuroinflammation-related diseases, such as Parkinson's disease.

Serum albumin level is associated with the recurrence of acute ischemic stroke.

BACKGROUND: Previous studies have confirmed that low serum albumin levels in acute ischemic stroke patients increased the risk for poor outcome and death, demonstrating the neuroprotective role of albumin. However, there are few studies investigating the relationship between albumin levels and recurrence of stroke. The aim of this study was to evaluate the effect of serum albumin level on the risk of recurrence in patients with acute ischemic stroke. METHODS: Seven hundred fifty-three consecutive patients with acute first-ever ischemic stroke were recruited in this study. Recurrent outcome was measured 1 year after stroke through home interviews (n = 692). RESULTS: Patients with recurrence had significantly lower serum albumin level than those without recurrence (37.07 ± 4.21 vs 38.91 ± 3.25). The multiple logistic regression adjustment for confounding factors showed that the association remained significant for patients in the second albumin quartile, the third quartile, and the fourth quartile compared with patients in the first quartile (adjusted odds ratio [aOR] = 0.543, 95% confidence interval [CI]: 0.307-0.959, P= .036; aOR = 0.449, 95% CI: 0.249-0.812, P= .008; and aOR = 0.290, 95% CI: 0.148-0.570, P < .001). CONCLUSION: Lower serum albumin level increases the risk of recurrence in patients with acute ischemic stroke, suggesting that serum albumin level might be used as an indicator for stroke recurrence.

Early neurological deterioration during the acute phase as a predictor of long-term outcome after first-ever ischemic stroke.

Early neurological deterioration (END) is associated with increased risk of functional disability and mortality. However, data are limited regarding the long-term risk of poor functional outcomes. Thus we explored the association between END and long-term outcomes in patients with acute ischemic stroke.A total of 1064 patients were enrolled with acute ischemic stroke who were consecutively admitted to the 3 stroke units of Huai-He Hospital, Kaifeng, China. END was defined as an increment change of at least one point in motor power or total National Institute of Health Stroke Scale (NIHSS) score deterioration ≥2 points within the first week after admission. We retrospectively assessed the risk factors of END and prospectively explored the relationship between END and the long-term outcomes by multivariable regression models after adjusting the potential confounding factors. Outcomes were evaluated at 18 months based on modified Rankin scale (MRS) scores.Approximately 32% of first-ever ischemic stroke patients experienced END during the acute phase. END was associated with diabetes (odds ratio [OR], 2.218; 95% confidence interval [CI] 1.619-3.037), NIHSS score at admission (OR, 1.052; 95% CI 1.023-1.082), C-reactive protein (CRP) levels (OR, 1.224; 95% CI 1.066-1.406]), and homocysteine (HCY) levels (OR, 1.203; 95% CI 1.061-1.365) after adjusting related factors, such as hypertension, diabetes, NIHSS at admission, and some blood laboratory values, including direct bilirubin, total cholesterol, low-density lipoprotein, glucose, CRP, HCY, and D-dimer levels. During the follow-up period, 52 (4.9%) patients died, 160 (15.0%) recrudesced, and 317 (29.8%) suffered poor outcomes. Multivariate logistic regression analyses revealed that poor outcome was associated with END (OR, 3.366; 95% CI 2.495-4.542), age (OR, 1.028; 95% CI 1.015-1.041), body mass index (OR, 1.096; 95% CI 1.051-1.144), coronary heart disease (OR, 1.637; 95% CI 1.108-2.416), and CRP (OR, 2.474; 95% CI 1.840-3.326).The risk factors of END are multifaceted. Diabetes, NIHSS score at admission, CRP, and HCY are independent predictors of END. In addition, the results of this study indicate that END is an important predictor of poor functional outcome.

H-Type Hypertension and C Reactive Protein in Recurrence of Ischemic Stroke.

Hypertension with high homocysteine (HHcy) (H-type hypertension) and C reactive protein (CRP) can increase the incidence of ischemic stroke. However, it is not clear whether recurrent ischemic stroke (RIS) is related to H-type hypertension and CRP. The present study investigated the correlation of H-type hypertension and CRP level with RIS. Totally, 987 consecutive patients with acute ischemic stroke were recruited in a teaching hospital in Henan province, China during March 2014 to March 2015. The demographic and clinical characteristics and blood biochemical parameters of patients were analyzed. Elevated levels of CRP and homocysteine (Hcy) were defined as >8.2 mg/L and 10 µmol/L, respectively. Among the 987 patients, 234 were RIS. Thirty-eight percent of RIS patients had elevated CRP level and 91.5% of RIS patients had HHcy. In multivariate analysis, adjusted odds ratio (OR) of RIS in patients aged ≥60 years was 1.576 (95% CI: 1.125-2.207), in male patients 1.935 (95% CI: 1.385-2.704), in patients with diabetes 1.463 (95% CI: 1.037-2.064), CRP levels 1.013 (95% CI: 1.006-1.019), simple hypertension 3.370 (95% CI: 1.15-10.183), and H-type hypertension 2.990 (95% CI: 1.176-7.600). RIS was associated with older age, male, diabetes, H-type hypertension and CRP. Controlling H-type hypertension and CRP level may reduce the risk of RIS.

The Relationship between C-Reactive Protein Level and Discharge Outcome in Patients with Acute Ischemic Stroke.

Previous studies showed that C-reactive protein (CRP), an inflammatory marker, was associated with stroke severity and long-term outcome. However, the relationship between the acute-phase CRP level and discharge outcome has received little attention. We prospectively studied 301 patients with acute ischemic stroke (over a period of two weeks) from two hospital stroke wards and one rehabilitation department in Henan, China. Patients' demographic and clinical data were collected and evaluated at admission. Poor discharge outcome was assessed in patients at discharge using the Modified Rankin Scale (MRS > 2). Multivariate logistic regression analysis was performed to determine the risk factors of poor discharge outcome after adjusting for potential confounders. Poor discharge outcome was observed in 78 patients (25.9%). Univariate analyses showed that factors significantly influencing poor discharge outcome were age, residence, recurrent acute ischemic stroke, coronary heart disease, the National Institutes of Health Stroke Scale (NIHSS) score at admission, non-lacunar stroke, time from onset of stroke to admission, CRP, TBIL (total bilirubin), direct bilirubin (DBIL), ALB (albumin), FIB (fibrinogen) and D-dimer (p < 0.05). After adjusting for age, residence, recurrent ischemic stroke, coronary heart disease, NIHSS score at admission, lacunar stroke, time from onset of stroke to admission, CRP, TBIL, DBIL, ALB, FIB and D-dimer, multivariate logistic regression analyses revealed that poor outcome at discharge was associated with recurrent acute ischemic stroke (OR, 2.115; 95% CI, 1.094-4.087), non-lacunar stroke (OR, 2.943; 95% CI, 1.436-6.032), DBIL (OR, 1.795; 95% CI, 1.311-2.458), and CRP (OR, 4.890; 95% CI, 3.063-7.808). In conclusion, the CRP level measured at admission was found to be an independent predictor of poor outcome at discharge. Recurrent acute ischemic stroke, non-lacunar stroke and DBIL were also significantly associated with discharge outcome in acute ischemic stroke.