scholarly journals Study on the Mechanism of mTOR-Mediated Autophagy during Electroacupuncture Pretreatment against Cerebral Ischemic Injury

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Zhou-Quan Wu ◽  
Su-yang Cui ◽  
Liang Zhu ◽  
Zhi-qing Zou
Keyword(s):  
Pearson Correlation ◽  
Specific Inhibitor ◽  
Ischemic Injury ◽  
Artery Occlusion ◽  
Protective Effects ◽  
Cerebral Ischemic Injury ◽  
Cerebral Ischemic ◽  
Cerebral Artery Occlusion ◽  
The Impact ◽  
The Brain

This study is aimed at investigating the association between the electroacupuncture (EA) pretreatment-induced protective effect against early cerebral ischemic injury and autophagy. EA pretreatment can protect cerebral ischemic and reperfusion injuries, but whether the attenuation of early cerebral ischemic injury by EA pretreatment was associated with autophagy is not yet clear. This study used the middle cerebral artery occlusion model to monitor the process of ischemic injury. For rats in the EA pretreatment group, EA pretreatment was conducted at Baihui acupoint before ischemia for 30 min for 5 consecutive days. The results suggested that EA pretreatment significantly increased the expression of autophagy in the cerebral cortical area on the ischemic side of rats. But the EA pretreatment-induced protective effects on the brain could be reversed by the specific inhibitor 3-methyladenine of autophagy. Additionally, the Pearson correlation analysis indicated that the impact of EA pretreatment on p-mTOR (2481) was negatively correlated with its impact on autophagy. In conclusion, the mechanism of EA pretreatment at Baihui acupoint against cerebral ischemic injury is mainly associated with the upregulation of autophagy expression, and its regulation of autophagy may depend on mTOR-mediated signaling pathways.

Gingko biloba Extract (EGb 761) Attenuates the Focal Cerebral Ischemic Injury-Induced Decrease in Astrocytic Phosphoprotein PEA-15 Levels

2011 ◽  
Vol 39 (05) ◽  
pp. 971-979 ◽  
Author(s):  
Phil-Ok Koh
Keyword(s):  
Apoptotic Cell ◽  
Ischemic Injury ◽  
Artery Occlusion ◽  
Male Rats ◽  
Egb 761 ◽  
Gingko Biloba ◽  
Proteomic Approach ◽  
Cerebral Ischemic Injury ◽  
Cerebral Ischemic ◽  
Cerebral Artery Occlusion

EGb 761 is an extract of Gingko biloba that is neuroprotective against focal cerebral ischemic injury. PEA-15 (phosphoprotein enriched in astrocytes 15) modulates cell proliferation and apoptosis. In this study, we investigated whether EGb 761 regulates the expression of PEA-15 and two phosphorylated forms of PEA-15 (Ser 104 and Ser 116) in middle cerebral artery occlusion (MCAO)-induced injury. Adult male rats were treated with vehicle or EGb 761 (100 mg/kg) prior to MCAO and cerebral cortices were collected 24 h after MCAO. A reduction in expression of PEA-15 and its phosphorylated forms induced by MCAO injury was detected using a proteomic approach. EGb 761 pretreatment prevented the ischemic injury-induced decrease in PEA-15 expression. Western blot analysis demonstrated that EGb 761 attenuates the injury-induced reduction in PEA-15, phospho-PEA-15 (Ser 104), phospho-PEA-15 (Ser 116). Phosphorylation of PEA-15 influences its anti-apoptotic function; a decrease in PEA-15 phosphorylation induces apoptotic cell death. The maintenance of PEA-15 phosphorylation by EGb 761 pretreatment during cerebral ischemic injury indicates that EGb 761 is a neuroprotective against cerebral ischemic injury.

scholarly journals CELSR1 Promotes Neuroprotection in Cerebral Ischemic Injury Mainly through the Wnt/PKC Signaling Pathway

2020 ◽  
Vol 21 (4) ◽  
pp. 1267 ◽  
Author(s):  
Li-Hong Wang ◽  
Geng-Lin Zhang ◽  
Xing-Yu Liu ◽  
Ai Peng ◽  
Hai-Yuan Ren ◽  
...  
Keyword(s):  
Motor Function ◽  
Cell Apoptosis ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Ischemic Injury ◽  
Artery Occlusion ◽  
Cerebral Ischemic Injury ◽  
Cerebral Ischemic ◽  
Cerebral Artery Occlusion

Cadherin epidermal growth factor (EGF) laminin G (LAG) seven-pass G-type receptor 1 (CELSR1) is a member of a special subgroup of adhesion G protein-coupled receptors. Although Celsr1 has been reported to be a sensitive gene for stroke, the effect of CELSR1 in ischemic stroke is still not known. Here, we investigated the effect of CELSR1 on neuroprotection, neurogenesis and angiogenesis in middle cerebral artery occlusion (MCAO) rats. The mRNA expression of Celsr1 was upregulated in the subventricular zone (SVZ), hippocampus and ischemic penumbra after cerebral ischemic injury. Knocking down the expression of Celsr1 in the SVZ with a lentivirus significantly reduced the proliferation of neuroblasts, the number of CD31-positive cells, motor function and rat survival and increased cell apoptosis and the infarct volume in MCAO rats. In addition, the expression of p-PKC in the SVZ and peri-infarct tissue was downregulated after ischemia/ reperfusion. Meanwhile, in the dentate gyrus of the hippocampus, knocking down the expression of Celsr1 significantly reduced the proliferation of neuroblasts; however, it had no influence on motor function, cell apoptosis or angiogenesis. These data indicate that CELSR1 has a neuroprotective effect on cerebral ischemia injury by reducing cell apoptosis in the peri-infarct cerebral cortex and promoting neurogenesis and angiogenesis, mainly through the Wnt/PKC pathway.

scholarly journals Echinochrome A Attenuates Cerebral Ischemic Injury through Regulation of Cell Survival after Middle Cerebral Artery Occlusion in Rat

Marine Drugs ◽  
2019 ◽  
Vol 17 (9) ◽  
pp. 501 ◽  
Author(s):  
Ran Kim ◽  
Daeun Hur ◽  
Hyoung Kyu Kim ◽  
Jin Han ◽  
Natalia P. Mishchenko ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Ischemic Injury ◽  
Artery Occlusion ◽  
Echinochrome A ◽  
Cerebral Ischemic Injury ◽  
Cerebral Ischemic ◽  
Cerebral Artery Occlusion

Of late, researchers have taken interest in alternative medicines for the treatment of brain ischemic stroke, where full recovery is rarely seen despite advanced medical technologies. Due to its antioxidant activity, Echinochrome A (Ech A), a natural compound found in sea urchins, has acquired attention as an alternative clinical trial source for the treatment of ischemic stroke. The current study demonstrates considerable potential of Ech A as a medication for cerebral ischemic injury. To confirm the effects of Ech A on the recovery of the injured region and behavioral decline, Ech A was administered through the external carotid artery in a rat middle cerebral artery occlusion model after reperfusion. The expression level of cell viability-related factors was also examined to confirm the mechanism of brain physiological restoration. Based on the results obtained, we propose that Ech A ameliorates the physiological deterioration by its antioxidant effect which plays a protective role against cell death, subsequent to post cerebral ischemic stroke.

Activation of astroglial CB1R mediates cerebral ischemic tolerance induced by electroacupuncture

2021 ◽  
pp. 0271678X2199439
Author(s):  
Cen Yang ◽  
Jingjing Liu ◽  
Jingyi Wang ◽  
Anqi Yin ◽  
Zhenhua Jiang ◽  
...  
Keyword(s):  
Endocannabinoid System ◽  
Artery Occlusion ◽  
Ischemic Tolerance ◽  
Protective Mechanisms ◽  
Promising Therapeutic Approach ◽  
Subsequent Activation ◽  
Cerebral Ischemic ◽  
Cerebral Artery Occlusion ◽  
The Brain

There are no effective treatments for stroke. The activation of endogenous protective mechanisms is a promising therapeutic approach, which evokes the intrinsic ability of the brain to protect itself. Accumulated evidence strongly suggests that electroacupuncture (EA) pretreatment induces rapid tolerance to cerebral ischemia. With regard to mechanisms underlying ischemic tolerance induced by EA, many molecules and signaling pathways are involved, such as the endocannabinoid system, although the exact mechanisms have not been fully elucidated. In the current study, we employed mutant mice, neuropharmacology, microdialysis, and virus transfection techniques in a middle cerebral artery occlusion (MCAO) model to explore the cell-specific and brain region-specific mechanisms of EA-induced neuroprotection. EA pretreatment resulted in increased ambient endocannabinoid (eCB) levels and subsequent activation of ischemic penumbral astroglial cannabinoid type 1 receptors (CB1R) which led to moderate upregulation of extracellular glutamate that protected neurons from cerebral ischemic injury. These findings provide a novel cellular mechanism of EA and a potential therapeutic target for ischemic stroke.

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

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
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.

N-Myc Downstream-Regulated Gene 2 (Ndrg2): A Critical Mediator of Estrogen-Induced Neuroprotection Against Cerebral Ischemic Injury

2021 ◽  
Author(s):  
Lixia Zhang ◽  
Yulong Ma ◽  
Min Liu ◽  
Miao Sun ◽  
Jin Wang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Neuroprotective Effect ◽  
Ischemic Injury ◽  
Artery Occlusion ◽  
Male Mice ◽  
Neuroprotective Effects ◽  
Female Mice ◽  
Ndrg2 Expression ◽  
Cerebral Ischemic Injury ◽  
Cerebral Ischemic

Abstract Growing evidence indicates that estrogen plays a pivotal role in neuroprotection against cerebral ischemia, but the molecular mechanism of this protection is still elusive. N-myc downstream‐regulated gene 2 (Ndrg2), an estrogen-targeted gene, has been shown to exert neuroprotective effects against cerebral ischemia in male mice. However, the role of Ndrg2 in the neuroprotective effect of estrogen remains unknown. In this study, we first detected NDRG2 expression levels in the cortex and striatum in both female and male mice with western blot analyses. We then detected cerebral ischemic injury by constructing middle cerebral artery occlusion and reperfusion (MCAO-R) models in Ndrg2 knockout or conditional knockdown female mice. We further implemented estrogen, ERα or ERβ agonist replacement in the ovariectomized (OVX) Ndrg2 knockouts or conditional knockdowns female mice, then tested for NDRG2 expression, glial fibrillary acidic protein (GFAP) expression, and extent of cerebral ischemic injury. We found that NDRG2 expression was significantly higher in female than in male mice in both the cortex and striatum. Ndrg2 knockouts and conditional knockdowns showed significantly aggravated cerebral ischemic injury in female mice. Estrogen and ERβ replacement treatment (DPN) led to NDRG2 upregulation in both the cortex and striatum of OVX mice. Estrogen and DPN also led to GFAP upregulation in OVX mice. However, the effect of estrogen and DPN in activating astrocytes was lost in Ndrg2 knockouts OVX mice and primary cultured astrocytes, but partially retained in conditional knockdowns OVX mice. Most importantly, we found that the neuroprotective effects of E2 and DPN against cerebral ischemic injury were lost in Ndrg2 knockouts OVX mice but partially retained in conditional knockdowns OVX mice. These findings demonstrate that estrogen alleviated cerebral ischemic injury via ERβ upregulation of Ndrg2, which could activate astrocytes, indicating that Ndrg2 is a critical mediator of E2-induced neuroprotection against cerebral ischemic injury.

Do RAS Inhibitors Protect the Brain from Cerebral Ischemic Injury?

2013 ◽  
Vol 9 (2) ◽  
pp. 86-92 ◽  
Author(s):  
Naohisa Hosomi ◽  
Akira Nishiyama ◽  
Masayasu Matsumoto
Keyword(s):  
Ischemic Injury ◽  
Cerebral Ischemic Injury ◽  
Cerebral Ischemic ◽  
The Brain ◽  
Ras Inhibitors

scholarly journals Protective effects of incensole acetate on cerebral ischemic injury

2012 ◽  
Vol 1443 ◽  
pp. 89-97 ◽  
Author(s):  
Arieh Moussaieff ◽  
Jin Yu ◽  
Hong Zhu ◽  
Sebastiano Gattoni-Celli ◽  
Esther Shohami ◽  
...  
Keyword(s):  
Ischemic Injury ◽  
Protective Effects ◽  
Cerebral Ischemic Injury ◽  
Cerebral Ischemic

scholarly journals Resveratrol Protects against Cerebral Ischemic Injury via Restraining Lipid Peroxidation, Transition Elements, and Toxic Metal Levels, but Enhancing Anti-Oxidant Activity

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1515
Author(s):  
Ming-Cheng Lin ◽  
Chien-Chi Liu ◽  
Yu-Chen Lin ◽  
Chin-Sheng Liao
Keyword(s):  
Lipid Peroxidation ◽  
Cerebral Ischemia ◽  
Toxic Metals ◽  
Ischemic Injury ◽  
Transition Elements ◽  
Anti Oxidant ◽  
Cerebral Ischemic Injury ◽  
Cerebral Ischemic ◽  
The Right ◽  
The Brain

Cerebral ischemia is related to increased oxidative stress. Resveratrol displays anti-oxidant and anti-inflammatory properties. The transition elements iron (Fe) and copper (Cu) are indispensable for the brain but overload is deleterious to brain function. Aluminum (Al) and arsenic (As) are toxic metals that seriously threaten brain health. This study was conducted to elucidate the correlation of the neuroprotective mechanism of resveratrol to protect cerebral ischemic damage with modulation of the levels of lipid peroxidation, anti-oxidants, transition elements, and toxic metals. Experimentally, 20 mg/kg of resveratrol was given once daily for 10 days. The cerebral ischemic operation was performed via occlusion of the right common carotid artery together with the right middle cerebral artery for 60 min followed by homogenization of the brain cortex and collection of supernatants for biochemical analysis. In the ligation group, levels of malondialdehyde, Fe, Cu, Al, and As increased but those of the anti-oxidants superoxide dismutase and catalase decreased. Pretreating rats with resveratrol before ischemia significantly reversed these effects. Our findings highlight the association of overload of Fe, Cu, As, and Al with the pathophysiology of cerebral ischemia. In conclusion, resveratrol protects against cerebral ischemic injury via restraining lipid peroxidation, transition elements, and toxic metals, but increasing anti-oxidant activity.

Protective Effects of Natrii Sulfas on Cerebral Focal Ischemia Induced by MCAO in Rats

2009 ◽  
Vol 37 (02) ◽  
pp. 273-293 ◽  
Author(s):  
Youngjoo Sohn ◽  
Ho Chang Kang ◽  
Kon Sik Kim ◽  
Sun-Min Park ◽  
Nak-Won Sohn ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Water Content ◽  
Brain Edema ◽  
Urine Volume ◽  
Artery Occlusion ◽  
Protective Effects ◽  
Fecal Weight ◽  
Physiological Indices ◽  
Cerebral Artery Occlusion ◽  
The Brain

This study examined the effect of Natrii sulfas, a treatment for stroke patients suffering constipation in Oriental medicine, on the physiological indices and brain edema of rats. Brain edema was induced by a middle cerebral artery occlusion (MCAO), Natrii sulfas was administered after the MCAO. At 3, 6, 15, 24, and 48 hours after reperfusion, the physiological indices such as the fecal weight, urine volume and water content in the stools were assessed. The edema index was measured 48 hours after reperfusion. At 48 hours, the expressions of iNOS, MMP9, VEGF, GFAP, Bax, Bcl-2, c-Fos, and HSP72 positive astrocytes were observed on the brain tissues by immunohistochemistry. Natrii sulfas significantly improved the decrease in fecal weight, urine volume and water content in the stool caused by the ischemic insult (p < 0.05) and attenuated the brain edema caused by the ischemia insult (p < 0.05). Natrii sulfas significantly down-regulated iNOS and MMP9 expressions and attenuated the astrocyte swelling due to brain edema in the penumbra of the cerebral cortex of MCAO rats. Natrii sulfas reduced the excess Bax and HSP72 expressions in ischemic brain, which was statistically significant in the penumbra of the cerebral cortex but not in the caudate putamen. These results suggest Natrii sulfas has a protective effect on ischemia-induced brain edema and improves the physiological symptoms.

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