stilbenes and Brain-Infarction

Dysfunction of energy metabolism can be a significant and fundamental pathophysiological basis for strokes. In studies of both humans and rodents, resveratrol, a natural polyphenol, has been reported to provide protection from cerebral ischemic injury by regulating expression of silent mating type information regulation 2 homolog 1 (SIRT1). However, direct evidence demonstrating that resveratrol exerts neuroprotection from cerebral ischemia injury by decreasing energy consumption is still lacking. Therefore, the aim of this study was to elucidate the mechanisms and signaling pathways through which resveratrol regulates energy metabolism in the ischemic brain, and to identify potential targets of resveratrol. ATP levels in brain tissues were detected by high performance liquid chromatography. SIRT1 and the phosphorylation of adenosine-monophosphate-activated protein kinase (P-AMPK) expressiones were evaluated by western blot. Levels of phosphodiesterase (PDEs) and cAMP were quantitated by real-time PCR and ELISA, respectively. Results showed that resveratrol significantly reduced the harmful effects of cerebral ischemic injury in vivo. Moreover, levels of ATP, p-AMPK, SIRT1, and cAMP were increased by resveratrol and PDE inhibitors. In conclusion, our findings indicate that resveratrol provides neuroprotection by inhibiting PDEs and regulating the cAMP/AMPK/SIRT1 pathway, which reduces ATP energy consumption during ischemia.

Topics: Adenosine Triphosphate; AMP-Activated Protein Kinases; Animals; Brain; Brain Infarction; Cyclic AMP; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme Inhibitors; Gene Expression Regulation; Male; Neuroprotective Agents; Phosphoric Diester Hydrolases; Phosphorylation; Rats; Rats, Sprague-Dawley; Resveratrol; Rolipram; Signal Transduction; Sirtuin 1; Stilbenes; Stroke

Both resveratrol (RV) and enriched environment (EE) exert beneficial effects on neurological functional recovery after an ischemic brain injury.. The neuroprotective effect of combined treatment of RV and EE was examined in a rat model of middle cerebral artery occlusion (MCAO), aiming to further promote neurological functional recovery.. The combined therapy of RV and EE clearly improved locomotor activity and behaviour examination, compared to the monotherapy of RV or EE alone. Stroke severity was also markedly ameliorated by the co-treatment. Mechanistic study revealed that the combined treatment reduced oxidative stress. Moreover, the detrimental ERK1/2 signalling upregulated by MCAO injury was markedly suppressed by the co-treatment, compared to RV or EE monotherapy.. Altogether, the combined therapy of RV and EE showed a clearly enhanced neuroprotective effect, compared to RV or EE monotherapy, which might be a new strategy for the treatment of ischemic brain injury.

Topics: Analysis of Variance; Animals; Brain Edema; Brain Infarction; Brain Injuries; Disease Models, Animal; Environment; Hydrogen Peroxide; Infarction, Middle Cerebral Artery; Locomotion; Male; MAP Kinase Signaling System; Neurologic Examination; Neuroprotective Agents; Nitric Oxide; Oxidative Stress; Rats; Rats, Wistar; Resveratrol; Stilbenes

Activation of microglia plays a crucial role in immune and inflammatory processes after ischemic stroke. Microglia is reported with two opposing activated phenotypes, namely, classic phenotype (M1) and the alternative phenotype (M2). Inhibiting M1 while stimulating M2 has been suggested as a potential therapeutic approach in the treatment of stroke.. In this study, we indicated that a novel natural anti-oxidant extracted from the Chinese plant Hopea hainanensis, malibatol A (MA), decreased the infarct size and alleviated the brain injury after mice middle cerebral artery occlusion (MCAO). MA inhibited expression inflammatory cytokines in not only MCAO mice but also lipopolysaccharide (LPS)-stimulated microglia. Moreover, treatment of MA decreased M1 markers (CD16, CD32, and CD86) and increased M2 markers (CD206, YM-1) while promoting the activation of nuclear receptor PPARγ.. MA has anti-inflammatory effects in MCAO mice in a PPARγ-dependent manner, making it a potential candidate for stroke treatment.

Topics: Animals; Benzamides; Brain Infarction; Calcium-Binding Proteins; Cell Polarity; Cells, Cultured; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Infarction, Middle Cerebral Artery; Lipopolysaccharides; Mice; Microfilament Proteins; Microglia; Neuroprotective Agents; Nitric Oxide Synthase Type II; PPAR gamma; Pyridines; Stilbenes; Time Factors

The present study was carried out to elucidate the neuroprotective effect and influence of resveratrol on the extracellular levels of neurotransmitter and neuromodulator during ischemia/reperfusion in rats. Male rats were divided into three groups: sham operation, ischemia treatment, and ischemia combined with resveratrol treatment (resveratrol-treated group, 30 mg/kg intraperitoneally for 7 days). Cerebral ischemia was induced by using the model of middle cerebral artery occlusion. The dialysates in hypothalamus were obtained by brain microdialysis technique. The levels of sixteen amino acids and amines in microdialysate were monitored by capillary electrophoresis analysis. This study shows that the ischemic infarcts were significantly reduced and neurological functions were improved in resveratrol-treated group compared to ischemia group. The analysis results demonstrate that chronic treatment with resveratrol remarkably reduced the release of excitatory neurotransmitter glutamate, aspartate and neuromodulator d-Serine during ischemia and reperfusion; and significantly increased the basal extracellular levels of inhibitory neurotransmitter gamma-amino-n-butyric acid, glycine and taurine. Chronic treatment with resveratrol also ameliorated O-phosphoethanolamine levels and excitotoxic index during ischemia and reperfusion. This study provides the first in vivo evidence that resveratrol could exert neuroprotective effect against ischemia injury by modulating the release of multiple neurotransmitters and neuromodulators during ischemia/reperfusion.

Topics: Animals; Antioxidants; Brain; Brain Infarction; Disease Models, Animal; Ethanolamines; Excitatory Postsynaptic Potentials; Extracellular Fluid; gamma-Aminobutyric Acid; Glutamic Acid; Glycine; Hypothalamus; Hypoxia-Ischemia, Brain; Infarction, Middle Cerebral Artery; Inhibitory Postsynaptic Potentials; Male; Neuroprotective Agents; Neurotransmitter Agents; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes; Treatment Outcome

We defined whether resveratrol administration during the acute phase of ischemic stroke reduces brain injury in mice. Infarct volumes were decreased significantly in both sexes with different doses of resveratrol (5mg/kg for males and 1mg/kg for females) administered 3h after ischemic stroke. Administration of resveratrol 6h after insult was also effective to decrease infarct volumes. Resveratrol suppressed expressions of IL-1β and TNF-α, microglial activation, and ROS production in the ischemic cortex. The findings suggest that the suppression of inflammation is partly associated with the neuroprotective effects of resveratrol, and resveratrol can be developed as a therapeutic drug for acute ischemic stroke.

Topics: Acute Disease; Animals; Brain Infarction; Brain Ischemia; Disease Models, Animal; Dose-Response Relationship, Immunologic; Female; Inflammation Mediators; Male; Mice; Mice, Inbred C57BL; Neuroprotective Agents; Reactive Oxygen Species; Resveratrol; Stilbenes; Stroke