This study investigated the effects of resveratrol (RSV) on retinal functions, glutamate transporters (GLAST) and glutamine synthetase (GS) expression in diabetic rats retina, and on glutamate uptake, GS activity, GLAST and GS expression in high glucose-cultured Müller cells. The electroretinogram was used to evaluate retinal functions. Müller cells cultures were prepared from 5- to 7-day-old Sprague-Dawley rats. The expression of GLAST and GS was examined by qRT-PCR, ELISA and western-blotting. Glutamate uptake was measured as (3)H-glutamate contents of the lysates. GS activity was assessed by a spectrophotometric assay. 1- to 7-month RSV administrations (5 and 10 mg/kg/day) significantly alleviated hyperglycemia and weight loss in diabetic rats. RSV administrations also significantly attenuated diabetes-induced decreases in amplitude of a-wave in rod response, decreases in amplitude of a-, and b-wave in cone and rod response and decreases in amplitude of OP2 in oscillatory potentials. 1- to 7-month RSV treatments also significantly inhibited diabetes-induced delay in OP2 implicit times in scotopic 3.0 OPS test. The down-regulated mRNA and protein expression of GLAST and GS in diabetic rats retina was prevented by RSV administrations. In high glucose-treated cultures, Müller cells' glutamate uptake, GS activity, GLAST and GS expression were decreased significantly compared with normal control cultures. RSV (10, 20, and 30 mmol/l) significantly inhibited the HG-induced decreases in glutamate uptake, GS activity, GLAST and GS expression (at least P < 0.05). These beneficial results suggest that RSV may be considered as a therapeutic option to prevent from diabetic retinopathy.

The aim of this study was to evaluate the anti-apoptosis effects of resveratrol (RSV) on diabetic rats retinal Müller cells in vivo and in vitro and to further investigate the roles of microRNA-29b (miR-29b)/specificity protein 1 (SP1) in the anti-apoptosis mechanism of RSV. Retina was obtained from normal and diabetic rats with or without RSV (5 and 10 mg/kg/day) treatments at 1-7 months. TdT-mediated dUTP-biotin nick end labeling (TUNEL) and Annexin V/PI staining were used to detect apoptosis. Immunofluorescence was used to assess distribution of SP1 in retina. MiR-29b and SP1 messenger RNA (mRNA) expression was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). SP1, Bax, and bcl-2 protein expression was evaluated by western blotting. Caspase-3 activity was detected by assay kit. Our study showed that the TUNEL-positive cells were mainly localized in the inner nuclear layer (INL) of retina and RSV administration effectively suppressed streptozotocin (STZ)-induced apoptosis of retinal cells in INL in vivo (P < 0.001). Our study also showed that RSV administration effectively suppressed high glucose (HG)-induced retinal Müller cells' apoptosis in vitro (P < 0.001). Furthermore, our study revealed that the diabetes-induced downregulated expression of miR-29b and upregulated expression of SP1 could be rescued by RSV in vivo and in vitro (P < 0.05). The anti-apoptosis effect and downregulated SP1 expression effect of RSV was prevented by miR-29b inhibitor (P < 0.05). MiR-29b mimic increased the above-mentioned effects of RSV (P < 0.001). These findings indicate that RSV is a potential therapeutic option for diabetic retinopathy (DR) and that miR-29b/SP1 pathway play roles in the anti-apoptosis mechanism of RSV.

Cerebral apoplexy is a disease caused by obstruction of the blood circulation in the brain. Evidence has indicated that inflammatory cytokines are implicated in ischaemic cerebral apoplexy and are regarded as a general cardiovascular risk factor, which may be a possible immediate trigger, a component of the response to tissue injury and a therapeutic target. The present study investigated changes of inflammatory cytokines and cells in patients with cerebral apoplexy at the intensive care unit (ICU). The plasma concentrations of inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-6, IL-8, IL-10, IL-1β and IL-17A were evaluated using ELISA. Changes in the plasma concentrations of inflammatory cells were detected by using flow cytometry. The results indicated that serum levels of TNF-α, IL-4, IL-8, IL-1β and IL-17A were upregulated in patients with cerebral apoplexy compared with those in healthy individuals, while those of IL-6 and IL-10 were downregulated. Furthermore, it was demonstrated that the plasma concentration of lymphocytes, granulocytes and mononuclear cells was decreased in patients with cerebral apoplexy in the ICU compared with that in healthy individuals. Of note, humoral as well as cellular inflammatory cytokines were evidently increased in patients with cerebral apoplexy in ICU. In conclusion, the present study provided evidence that inflammatory cytokines and inflammatory cells are upregulated, while anti-inflammatory cytokines are downregulated in patients with cerebral apoplexy in an ICU setting. These results suggest that anti-inflammatory interventions may be beneficial either in the prevention or acute treatment of patients with cerebral apoplexy.

Objective: Previous studies have shown that the neuron-specific- enolase (NSE), S100B protein (S100B) and matrix metalloproteinase-9 (MMP9) are specific markers for studying cerebral injury. This study was aimed to demonstrate these biomarkers for their correlation with reperfusion after carotid artery stenting (CAS). Methods: In this study, a total of 44 patients who were diagnosed unilateral carotid artery stenosis by digital subtraction angiography (DSA) and underwent CAS, were selected as the operation groups. The patients' blood samples were collected at three different time points: T1, prior to operation; T2, next morning after operation (24 hours); T3, three days after operation (72 hours); All of the patients with the operation received computed tomography perfusion (CTP) at T1 and T3. The second group of 12 patients, who were excluded for carotid artery stenosis by DSA, were assigned to be the control group; Blood samples of these patients were collected at T1. The concentrations of NSE, S100B and MMP9 in serum from patients of both groups were detected by ELISA. Results: All of the operations were implanted in stents successfully without complications. (1) After CAS, rCBF increased while rMTT and rTTP decreased. (2) The concentrations of NSE, S100B and MMP9 in the serum decreased gradually (T1>T2>T3). There was no significant difference between the control group and the operation group at T1 (P>0.05) on their concentrations of NSE, S100B and MMP9 in the serum. When compared among the operation groups, the concentrations of NSE, S100B and MMP9 in the serum at T1 and T3 showed significant difference (P < 0.05). (3) Correlation analysis among the operation groups indicated that NSE, S100B, MMP9 and rCBF were positively correlated before operation (r = 0.69, 0.58 and 0.72, respectively, P < 0.05), as well as after operation (r = 0.75, 0.65 and 0.60, respectively, P < 0.05). Conclusion: We concluded that the concentrations of NSE, S100B and MMP9 in serum decreased with the improvement of cerebral reperfusion after CAS. NSE, S100B and MMP9 can be used as laboratory biochemical markers to evaluate the improvement of reperfusion after CAS. The results very well complement the imaging methods, such as CTP.

Astrocytes-mediated neuroinflammation has been involved in the process of several neurodegenerative diseases. Ramelteon is a novel agonist of melatonin receptors and licensed for the management of insomnia. In this study, our results demonstrate that Ramelteon ameliorated lipopolysaccharide (LPS)-induced inflammatory responses in astrocytes. First, we found that the optimized incubation concentrations of Ramelteon applied in the present study were 50 and 100 nM. Second, treatment with Ramelteon reduced expressions of IL-6, TNF-α, and IL-1β. Additionally, Ramelteon prevented an LPS-induced increase in the expressions of iNOS, COX-2, NO, and PGE2. Importantly, we found that Ramelteon reduced the expression of GFAP. Mechanistically, we found that Ramelteon inhibited the TLR4/IκBα/NF-κB p65 axis. Notably, the protective effects of Ramelteon were verified in an in vivo rodent model. Based on these findings, we concluded that Ramelteon might prevent LPS-induced damage in astrocytes.