Neural-protective effects of GM1 in experimental models of cerebral ischemia

Cardiovascular disease (CVD) is the leading cause of mortality worldwide, and it is well known that end-stage renal disease (ESRD) is a profound consequence of the progression of CVD. Present treatments only slow CVD progression to ESRD, and it is imperative that new therapeutic strategies are developed to prevent the incidence of ESRD. Because epoxyeicosatrienoic acids (EETs) have been shown to elicit reno-protective effects in hypertensive animal models, the current review will focus on addressing the reno-protective mechanisms of EETs in CVD. The cytochrome P-450 epoxygenase catalyzes the oxidation of arachidonic acid to EETs. EETs have been identified as endothelium-derived hyperpolarizing factors (EDHFs) with vasodilatory, anti-inflammatory, antihypertensive, and antiplatelet aggregation properties. EETs also have profound effects on vascular migration and proliferation and promote angiogenesis. The progression of CVD has been linked to decreased EETs levels, leading to the concept that EETs should be therapeutically targeted to prevent end-organ damage associated with CVD. However, EETs are quickly degraded by the enzyme soluble epoxide hydrolase (sEH) to their less active diols, dihydroxyeicosatrienoic acids (DHETs). As such, one way to increase EETs level is to inhibit their degradation to DHETs by using sEH inhibitors. Inhibition of sEH has been shown to effectively reduce blood pressure and organ damage in experimental models of CVD. Another approach to target EETs is to develop EET analogs with improved solubility and resistance to auto-oxidation and metabolism by sEH. For example, stable ether EET analogs dilate afferent arterioles and lower blood pressure in hypertensive rodent animal models. EET agonists also improve insulin signaling and vascular function in animal models of metabolic syndrome.

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Effects of Propentofylline on Hypoxia—Hypoglycemia-Induced Calcium Accumulation in Gerbil Hippocampal Slices

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1992.41 ◽

1992 ◽

Vol 12 (2) ◽

pp. 301-305 ◽

Cited By ~ 12

Author(s):

Fumito Kadoya ◽

Akira Mitani ◽

Tatsuru Arai ◽

Kiyoshi Kataoka

Keyword(s):

Cerebral Ischemia ◽

Intracellular Calcium ◽

Neuronal Damage ◽

Hippocampal Slices ◽

Dependent Manner ◽

Protective Effects ◽

Calcium Accumulation ◽

Xanthine Derivative ◽

Acute Increase ◽

Dose Dependent

The xanthine derivative propentofylline (HWA 285) has been reported to show protective effects against neuronal damage induced by cerebral ischemia. In the present study, microfluorometry was used to investigate the effect of propentofylline on the hypoxia–hypoglycemia-induced intracellular calcium accumulation in gerbil hippocampal slices. When slices were superfused with hypoxic–hypoglycemic medium that did not contain propentofylline, an acute increase in calcium accumulation was detected 75–200 s (mean latency of 123 s) after the beginning of hypoxia–hypoglycemia. When slices were superfused with hypoxic–hypoglycemic mediums that contained 10 μ M, 100 μ M, and 1 m M propentofylline, the latency of the acute increase in calcium accumulation was prolonged in all subregions of the hippocampus in a dose-dependent manner: mean latencies in field CA1 were 146, 168, and 197 s after hypoxia–hypoglycemia, respectively. This retardation in calcium accumulation may be involved in the mechanisms by which propentofylline diminishes ischemic injury.

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Curcumin Protects Neuron against Cerebral Ischemia-Induced Inflammation through Improving PPAR-Gamma Function

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/470975 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 14

Author(s):

Zun-Jing Liu ◽

Wei Liu ◽

Lei Liu ◽

Cheng Xiao ◽

Yu Wang ◽

...

Keyword(s):

Cerebral Ischemia ◽

Neuronal Damage ◽

Infarct Volume ◽

Critical Role ◽

Ischemic Injury ◽

Ppar Gamma ◽

Neurological Deficits ◽

Protective Effects ◽

Cerebral Ischemic Injury ◽

Cerebral Ischemic

Cerebral ischemia is the most common cerebrovascular disease worldwide. Recent studies have demonstrated that curcumin had beneficial effect to attenuate cerebral ischemic injury. However, it is unclear how curcumin protects against cerebral ischemic injury. In the present study, using rat middle cerebral artery occlusion model, we found that curcumin was a potent PPARγagonist in that it upregulated PPARγexpression and PPARγ-PPRE binding activity. Administration of curcumin markedly decreased the infarct volume, improved neurological deficits, and reduced neuronal damage of rats. In addition, curcumin suppressed neuroinflammatory response by decreasing inflammatory mediators, such as IL-1β, TNF-α, PGE2, NO, COX-2, and iNOS induced by cerebral ischemia of rats. Furthermore, curcumin suppressed IκB degradation that was caused by cerebral ischemia. The present data also showed that PPARγinteracted with NF-κB-p65 and thus inhibited NF-κB activation. All the above protective effects of curcumin on cerebral ischemic injury were markedly attenuated by GW9662, an inhibitor of PPARγ. Our results as described above suggested that PPARγinduced by curcumin may play a critical role in protecting against brain injury through suppression of inflammatory response. It also highlights the potential of curcumin as a therapeutic agent against cerebral ischemia.

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