Contra-Directional Expression of Plasma Superoxide Dismutase with Lipoprotein Cholesterol and High-Sensitivity C-reactive Protein as Important Markers of Parkinson's Disease Severity.

Aim: Oxidative stress and inflammation play critical roles in the neuropathogenesis of PD. We aimed to evaluate oxidative stress and inflammation status by measuring serum superoxide dismutase (SOD) with lipoprotein cholesterol and high-sensitivity C-reactive protein (hsCRP) respectively in PD patients, and explore their correlation with the disease severity. Methods: We performed a cross-sectional study that included 204 PD patients and 204 age-matched healthy controls (HCs). Plasma levels of SOD, hsCRP, total cholesterol, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured. A series of neuropsychological assessments were performed to rate the severity of PD. Results: The plasma levels of SOD (135.7 ± 20.14 vs. 147.2 ± 24.34, P < 0.0001), total cholesterol, HDL-C and LDL-C in PD were significantly lower than those in HCs; the hsCRP level was remarkably increased in PD compared to HC (2.766 ± 3.242 vs. 1.637 ± 1.597, P < 0.0001). The plasma SOD was negatively correlated with the hsCRP, while positively correlated with total cholesterol, HDL-C, and LDL-C in PD patients. The plasma SOD were negatively correlated with H&Y, total UPDRS, UPDRS (I), UPDRS (II), and UPDRS (III) scores, but positively correlated with MoCA and MMSE scores. Besides, hsCRP was negatively correlated with MoCA; while total cholesterol, HDL-C and LDL-C were positively correlated with the MoCA, respectively. Conclusion: Our findings suggest that lower SOD along with cholesterol, HDL-C and LDL-C, and higher hsCRP levels might be important markers to assess the PD severity. A better understanding of SOD and hsCRP may yield insights into the pathogenesis of PD.

Effect of using fluoxetine at different time windows on neurological functional prognosis after ischemic stroke.

PURPOSE: To evaluate the effect of using fluoxetine at different time intervals after ischemic stroke on neurological functional prognosis in China. METHODS: The patients enrolled were randomly allocated to three groups. Group A received fluoxetine 20 mg/day immediately; group B received fluoxetine 20 mg/day 7 days after enrollment; and group C did not receive fluoxetine. The therapeutic duration of fluoxetine was 90 days and the follow-up period was 180 days. RESULTS: The mean NIHSS score at day 90 was significantly lower in group A than group C (P = 0.005), while at day 180, the mean score in group A was significantly lower than groups B and C (P = 0.035, P = 0.000), respectively. The mean BI score at day 90 was significantly higher in group A than group C (P = 0.001), while at day 180, the mean score in group A was significantly higher than groups B and C (P = 0.036, P = 0.000), respectively. Regression analysis indicated that lower NIHSS score and higher BI score at day 180 were attributed to the early administration of fluoxetine. CONCLUSIONS: In patients with ischemic stroke, early administration of fluoxetine may improve the neurological functional prognosis.

Decreased leukocyte telomere length (LTL) is associated with stroke but unlikely to be causative.

AIMS: Interindividual variability in telomere length is highly heritable. Leukocyte telomere length (LTL) shortening has been shown to be associated with the process of atherosclerosis. But whether the inheritance of LTL is related to stroke is still unclear. The aim of this study was to test if telomere shortening was associated with stroke and whether this association was mainly due to inheritance or acquired cardiovascular risk factors. METHODS: Our study was focused on stroke in patients and their siblings. 450 subjects were recruited into this study: 150 patients with ischemic stroke as case group, 150 siblings of patients free of stroke (sibling group) and 150 healthy people as normal control. LTL was measured by real-time Polymerase Chain Reactions. The association between LTL and the cardiovascular risk factors was also determined. RESULTS: A significant decrease of LTL was found in case group when comparing with sibling (0.92±0.77 vs 1.68±1.24, p<0.001) and normal groups (0.92±0.77 vs 1.95±1.07, p<0.001), but no significant difference was found between sibling group and healthy control (p = 0.330). Shorter telomere length was independently associated with hypertension (p = 0.029, OR = 2.189, 95%CI:1.084-4.421), recent social pressure (p = 0.001, OR = 3.121, 95%CI:1.597-6.101), age (p = 0.004, OR = 1.055, 95%CI:1.017-1.093), HDL (p = 0.022, OR = 0.227, 95%CI:0.064-0.810) and diabetes (p = 0.018, OR = 3.174, 95%CI:1.221-8.252). Additionally, shortened length of telomere (p = 0.017, OR = 3.996, 95%CI:1.283-12.774) was an independent risk biomarker for stroke among case and sibling groups. CONCLUSION: The present study has demonstrated that decreased LTL might be associated with ischemic stroke but unlikely to be causative.

Oncosis, the possible cell death pathway in astrocytes after focal cerebral ischemia.

Swelling of astrocytes at early stage of cerebral ischemia has been reported, however, the fate and the cell death pathway of astrocytes are still unclear. Focal cerebral ischemia was induced in Sprague-Dawley rats by permanent occlusion of middle cerebral artery for 3 to 48 h. Haematoxylin and eosin (HE) staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), glial fibrillary acidic protein (GFAP), caspase-3 immunostaining, and double-staining with TUNEL and GFAP were carried out on consecutive sections. The ultrastructure was revealed by electron microscopy. Using electron microscope, apoptotic neurons were confirmed with condensed chromatin and apoptotic bodies. In the core of the infarct, clumps of heterochromatin around the edge of nucleus, vacuolar degeneration of the nucleus and leakage of chromatin were demonstrated at 3, 6, and 12 h respectively in the swelling astrocytes, which accorded with the process of oncosis; in the peripheral zone of the infarct, reactive astrocytes with nuclear membranes preserved demonstrated increased cell size and number and coexisted with oncotic astrocytes. Scattered GFAP-positive cells and ubiquitous caspase-3-positive cells were found in the core after 12 h following cerebral ischemia, and no cells positive for double-staining with TUNEL and GFAP were found in the ischemic regions, indicating that most GFAP-positive astrocytes did not die by apoptosis. Findings from present study demonstrate that after cerebral ischemia, oncosis may be the possible cell death pathway of astrocytes in the ischemic region, and oncotic astrocytes coexist with reactive astrocytes in the peripheral zone.

Effects of aspirin on atherosclerosis and the cyclooxygenase-2 expression in atherosclerotic rabbits.

BACKGROUND: Atherosclerosis is a complex vascular inflammatory disease. Aspirin is a mainstay in the prevention of vascular complications of atherosclerosis. In this study, the effectiveness of aspirin in suppressing atherosclerosis and the inflammation process was evaluated in rabbits fed with a high fat diet. METHODS: Eighteen male New Zealand rabbits were randomly divided into 3 groups: control group, untreated cholesterol-fed group, aspirin treated cholesterol-fed group, which were fed for 12 weeks. After 12 weeks, the aorta was harvested for pathologic morphology observation. Immunohistochemical analysis of cyclooxygenase-2 (COX-2), macrophage and vascular smooth muscle cell (VSMC) was performed. The statistical analysis was performed by the statistical program SPSS10.0. RESULTS: The aorta plaque/intima size (P/I) by pathologic morphology observation was 0%, (59.6 +/- 13.7)% and (36.3 +/- 16.5)% in the control, untreated cholesterol-fed group and aspirin treated group, respectively. The maximum plaque thickness, the degree of artery stenosis and the proportion of the intimal circumference occupied by atheroma of the 3 groups were significantly different from each other (P < 0.01). The expression of COX-2 and macrophage in plaque of the aspirin treated group were decreased compared with that in untreated cholesterol-fed group. However, no difference was found in the expression of VSMC between the aspirin treated and the untreated cholesterol-fed group. CONCLUSION: The mechanism of atherosclerosis suppression by aspirin in cholesterol-fed rabbits is related to the inhibition of COX-2 expression together with the reduced inflammation followed by, but not related to the hypolipidemic effects.