scholarly journals Eriodictyol Attenuates MCAO-Induced Brain Injury and Neurological Deficits via Reversing the Autophagy Dysfunction

2021 ◽  
Vol 15 ◽  
Author(s):  
Chuanxiang Wang ◽  
Zhequan Ma ◽  
Zuqiang Wang ◽  
Shuping Ming ◽  
Yanbing Ding ◽  
...  
Keyword(s):  
Brain Injury ◽  
Protective Effect ◽  
Neuroprotective Effect ◽  
Artery Occlusion ◽  
Neurological Deficits ◽  
High Dose ◽  
Neural Function ◽  
Nissl Staining ◽  
Adult Rats ◽  
Kg Medium

The present study was designed to investigate the protective effect of eriodictyol on MCAO-induced brain injury and its regulation of neural function and to explore the mechanism of its regulation of autophagy in rats. Brain injury was induced by middle cerebral artery occlusion (MCAO) in adult rats and pretreated with eriodictyol (low dose: 20 mg/kg; medium dose: 40 mg/kg; high dose: 80 mg/kg) or saline. Rats in the treatment group had a smaller volume of infarction and improved neurological outcome and reduced the latency to the platform, increased the time spent in the correct quadrant compared to MCAO rats pretreated with saline. ELISA kits results confirmed that eriodictyol reduced the inflammatory response induced by MCAO. The results of apoptosis and proliferation by Nissl staining and immunofluorescence detection indicated that eriodictyol could inhibit apoptosis and promote the proliferation in MCAO rats. The expressions of LC3, ATG5, p62, and Beclin1 were used to evaluate the autophagy, as well as the reversal of the autophagy activator (rapamycin) on the neuroprotective effect of eriodictyol, which suggested that the protective effect of eriodictyol on brain injury may be related to the inhibition of autophagy. In summary, we, therefore, suggested that eriodictyol could reduce the inflammation response of brain injury and inhibit neuroapoptosis, directly affecting autophagy to alleviate brain injury. It will provide theoretical support for eriodictyol in the treatment of ischemic stroke.

scholarly journals Quercetin attenuates the reduction of parvalbumin in middle cerebral artery occlusion animal model

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Dong-Ju Park ◽  
Ju-Bin Kang ◽  
Fawad-Ali Shah ◽  
Phil-Ok Koh
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Neuroprotective Effect ◽  
Neuronal Cell ◽  
Artery Occlusion ◽  
Male Rats ◽  
Neurological Deficits ◽  
Glutamate Toxicity ◽  
Cerebral Artery Occlusion

Abstract Background Calcium is a critical factor involved in modulation of essential cellular functions. Parvalbumin is a calcium buffering protein that regulates intracellular calcium concentrations. It prevents rises in calcium concentrations and inhibits apoptotic processes during ischemic injury. Quercetin exerts potent antioxidant and anti-apoptotic effects during brain ischemia. We investigated whether quercetin can regulate parvalbumin expression in cerebral ischemia and glutamate toxicity-induced neuronal cell death. Adult male rats were treated with vehicle or quercetin (10 mg/kg) 30 min prior to middle cerebral artery occlusion (MCAO) and cerebral cortical tissues were collected 24 h after MCAO. We used various techniques including Western blot, reverse transcription-PCR, and immunohistochemical staining to elucidate the changes of parvalbumin expression. Results Quercetin ameliorated MCAO-induced neurological deficits and behavioral changes. Moreover, quercetin prevented MCAO-induced a decrease in parvalbumin expression. Conclusions These findings suggest that quercetin exerts a neuroprotective effect through regulation of parvalbumin expression.

Abstract WP272: A Powerful Combination Therapy for Stroke: Post-Ischemia Ethanol Administration and Normobaric Oxygenation on Ischemic Rats

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Christopher Sy ◽  
Xiaokun Geng ◽  
Paul Fu ◽  
Changya Peng ◽  
Vance Fredrickson ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Protein Expression ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Artery Occlusion ◽  
Neurological Deficits ◽  
Ethanol Administration ◽  
Acute Administration ◽  
Sprague Dawley ◽  
Acute Cerebral Ischemia

Objectives: Normobaric oxygenation (NBO) has been reported to be neuroprotective against acute cerebral ischemia. Recently, a clinical trial was terminated because beneficial outcomes were not definitive. Our recent study ( Stroke. 2012 43(1):205-10 ) demonstrated a strong neuroprotective effect induced by acute administration of ethanol (EtOH) at 1.5g/kg. In this study, we assessed the therapeutic influence of EtOH in combination with NBO. Methods: Sprague-Dawley rats were subjected to right middle cerebral artery occlusion for 2h. Ischemic animals received either an intraperitoneal injection of EtOH (1.0g/kg), a course of NBO (100% for 2h), or a combination of both immediately prior to reperfusion onset. Brain injury was determined by infarct volume and behavioral outcomes at 48h post-reperfusion. Metabolic dysfunction was investigated by assessing ADP/ATP ratios, reactive oxygen species (ROS) levels, NADPH oxidase (NOX) activity, and protein expression of NOX subunits (p47 phox , gp91 phox , and p67 phox ), as well as the protein expression and enzyme activity of pyruvate dehydrogenase (PDH), at both 3h and 24h after reperfusion. Results: Combination therapy led to a significant decrease in infarct volumes (Saline: 48±4%, EtOH: 38±3%, NBO: 37±4%, Combination: 19±3% ) and in neurological deficits (Belayev Scale 0-12, Saline: 8.4±0.7; EtOH: 6.5±0.7; NBO: 6.4±0.6; Combination: 4.4±0.3 ). At 3h and 24h post-reperfusion the decrease in ADP/ATP ratio was significantly enhanced, reflecting a preservation of cellular energy. A greater decrease in NOX activity and protein expression was observed, in association with decreased ROS levels, suggesting that improved glycolysis may contribute to neuroprotection. PDH activity and protein expression was dramatically increased, making the facilitation of aerobic metabolism a probable mechanism for preserving cellular ATP. Conclusions: Our findings demonstrate that a synergistic relationship exists between EtOH and NBO. Both are promising neuroprotective agents when used together, even at low doses. Moreover, both are inexpensive, widely available, easy to administer, and have little side effects. Thus, combination therapy could be an effective and efficient approach to future stroke treatments.

scholarly journals Cerebroprotective Effect ofMoringa oleiferaagainst Focal Ischemic Stroke Induced by Middle Cerebral Artery Occlusion

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Woranan Kirisattayakul ◽  
Jintanaporn Wattanathorn ◽  
Terdthai Tong-Un ◽  
Supaporn Muchimapura ◽  
Panakaporn Wannanon ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ischemic Stroke ◽  
Protective Effect ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Brain Infarction ◽  
Artery Occlusion ◽  
High Dose ◽  
Infarction Volume ◽  
Male Wistar Rats

The protection against ischemic stroke is still required due to the limitation of therapeutic efficacy. Based on the role of oxidative stress in stroke pathophysiology, we determined whetherMoringa oleifera, a plant possessing potent antioxidant activity, protected against brain damage and oxidative stress in animal model of focal stroke.M. oleiferaleaves extract at doses of 100, 200 and 400 mg·kg−1was orally given to male Wistar rats (300–350 g) once daily at a period of 2 weeks before the occlusion of right middle cerebral artery (Rt.MCAO) and 3 weeks after Rt.MCAO. The determinations of neurological score and temperature sensation were performed every 7 days throughout the study period, while the determinations of brain infarction volume, MDA level, and the activities of SOD, CAT, and GSH-Px were performed 24 hr after Rt.MCAO. The results showed that all doses of extract decreased infarction volume in both cortex and subcortex. The protective effect of medium and low doses of extract in all areas occurred mainly via the decreased oxidative stress. The protective effect of the high dose extract in striatum and hippocampus occurred via the same mechanism, whereas other mechanisms might play a crucial role in cortex. The detailed mechanism required further exploration.

scholarly journals Depleting SOX2 improves ischemic stroke via lncRNA PVT1/microRNA-24-3p/STAT3 axis

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Zhongjun Chen ◽  
Tieping Fan ◽  
Xusheng Zhao ◽  
Zhichen Zhang
Keyword(s):  
Oxidative Stress ◽  
Ischemic Stroke ◽  
Brain Injury ◽  
Water Content ◽  
Artery Occlusion ◽  
Neurological Deficits ◽  
Neuron Survival ◽  
Non Coding Rna ◽  
Cerebral Artery Occlusion ◽  
And Oxidative Stress

Abstract Objectives Studies have widely explored in the filed of ischemic stroke (IS) with their focus on transcription factors. However, few studies have pivoted on sex determining region Y-box 2 (SOX2) in IS. Thus, this study is launched to figure out the mechanisms of SOX2 in IS. Methods Rat middle cerebral artery occlusion (MCAO) was established as a stroke model. MCAO rats were injected with depleted SOX2 or long non-coding RNA plasmacytoma variant translocation 1 (PVT1) to explore their roles in neurological deficits, cerebral water content, neuron survival, apoptosis and oxidative stress. The relationship among SOX2, PVT1, microRNA (miR)-24-3p and signal transducer and activator of transcription 3 (STAT3) was verified by a series of experiments. Results SOX2, PVT1 and STAT3 were highly expressed while miR-24-3p was poorly expressed in cerebral cortex tissues of MCAO rats. Depleted SOX2 or PVT1 alleviated brain injury in MCAO rats as reflected by neuronal apoptosis and oxidative stress restriction, brain water content reduction, and neurological deficit and neuron survival improvements. Overexpression of PVT1 functioned oppositely. Restored miR-24-3p abolished PVT1 overexpression-induced brain injury in MCAO rats. SOX2 directly promoted PVT1 expression and further increased STAT3 by sponging miR-24-3p. Conclusion This study presents that depleting SOX2 improves IS via PVT1/miR-24-3p/STAT3 axis which may broaden our knowledge about the mechanisms of SOX2/PVT1/miR-24-3p/STAT3 axis and provide a reference of therapy for IS.

scholarly journals Destructive Effects of Pyroptosis on Homeostasis of Neuron Survival Associated with the Dysfunctional BBB-Glymphatic System and Amyloid-Beta Accumulation after Cerebral Ischemia/Reperfusion in Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Zhongkuan Lyu ◽  
Yuanjin Chan ◽  
Qiyue Li ◽  
Qiang Zhang ◽  
Kaili Liu ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Amyloid Beta ◽  
Neuronal Damage ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Neurological Deficits ◽  
Specific Marker ◽  
Nissl Staining ◽  
Glymphatic System ◽  
Cerebral Ischemia Reperfusion

Neuroinflammation-related amyloid-beta peptide (Aβ) accumulation after cerebral ischemia/reperfusion (I/R) accounts for cerebral I/R injuries and poststroke dementia. Recently, pyroptosis, a proinflammatory cell death, has been identified as a crucial pathological link of cerebral I/R injuries. However, whether pyroptosis acts as a trigger of Aβ accumulation after cerebral I/R has not yet been demonstrated. Blood-brain barrier (BBB) and glymphatic system mediated by aquaporin-4 (AQP-4) on astrocytic endfeet are important pathways for the clearance of Aβ in the brain, and pyroptosis especially occurring in astrocytes after cerebral I/R potentially damages BBB integrity and glymphatic function and thus influences Aβ clearance and brain homeostasis. In present study, the method of middle cerebral artery occlusion/reperfusion (MCAO/R) was used for building models of focal cerebral I/R injuries in rats. Then, we used lipopolysaccharide and glycine as the agonist and inhibitor of pyroptosis, respectively, Western blotting for detections of pyroptosis, AQP-4, and Aβ1-42 oligomers, laser confocal microscopy for observations of pyroptosis and Aβ locations, and immunohistochemical stainings of SMI 71 (a specific marker for BBB integrity)/AQP-4 and Nissl staining for evaluating, respectively, BBB-glymphatic system and neuronal damage. The results showed that pyroptosis obviously promoted the loss of BBB integrity and AQP-4 polarization, brain edema, Aβ accumulation, and the formation of Aβ1-42 oligomers and thus increased neuronal damage after cerebral I/R. However, glycine could inhibit cerebral I/R-induced pyroptosis by alleviating cytomembrane damage and downregulating expression levels of cleaved caspase-11/1, N-terminal gasdermin D, NLRP3 (nucleotide-binding domain, leucine-rich repeat containing protein 3), interleukin-6 (IL-6) and IL-1β and markedly abate above pathological changes. Our study revealed that pyroptosis is a considerable factor causing toxic Aβ accumulation, dysfunctional BBB-glymphatic system, and neurological deficits after cerebral I/R, suggesting that targeting pyroptosis is a potential strategy for the prevention of ischemic stroke sequelae including dementia.

scholarly journals Neuroprotective effect of astrocyte-derived IL-33 in neonatal hypoxic-ischemic brain injury

2019 ◽  
Author(s):  
Mengya Jiao ◽  
Xiangyong Li ◽  
Xiaodi Wang ◽  
Liying Chen ◽  
Baohong Yuan ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Brain Injury ◽  
Neurotrophic Factor ◽  
Inflammatory Responses ◽  
Neuroprotective Effect ◽  
Brain Infarction ◽  
Neurological Deficits ◽  
Dependent Manner ◽  
Ischemic Brain

Abstract Background: Interleukin-33 (IL-33) is a well-recognized pleiotropic cytokine which plays crucial roles in immune regulation and inflammatory responses. Recent studies suggest that IL-33 and its receptor ST2 are involved in the pathogenesis of neurological diseases. Here, we explore the effect of IL-33/ST2 signaling in neonatal hypoxic-ischemic (HI) brain injury and elucidate the underlying mechanisms of action. Methods: The brain HI model was established in neonatal C57BL/6 mice by left common carotid artery occlusion with 90 min hypoxia, and treated with IL-33 at a dose of 0.2 μg/day i.p. for three days. TTC staining and neurobehavioral observation were used to evaluate the HI brain injury. Immunofluorescence and flow cytometry were applied to determine the expression of IL-33 and its receptor ST2 on brain CNS cells, cell proliferation and apoptosis. OGD experiment was used to assay the viability of astrocytes and neurons. RT-qPCR was used to measure the expression of neurotrophic factor-associated genes. Results: The expression level of IL-33 was markedly enhanced in astrocytes 24 h after cerebral HI in neonatal mice. Exogenous delivery of IL-33 significantly alleviated brain injury 7 d after HI, whereas ST2 deficiency exacerbated brain infarction and neurological deficits post HI. Flow cytometry analyses demonstrated high levels of ST2 expression on astrocytes, and the expression of ST2 was further elevated after HI. Intriguingly, IL-33 treatment apparently improved astrocyte response and attenuated HI-induced astrocyte apoptosis through ST2 signaling pathways. Further in vitro studies revealed that IL-33-activated astrocytes released a series of neurotrophic factors, which are critical for raising neuronal survival against oxygen glucose deprivation. Conclusions: The activation of IL-33/ST2 signaling in the ischemic brain improves astrocyte response, which in turn affords protection to ischemic neurons in a glial-derived neurotrophic factor-dependent manner.

Neuroprotective effect of high-dose albumin therapy against global ischemic brain injury in rats

1999 ◽  
Vol 845 (1) ◽  
pp. 107-111 ◽  
Author(s):  
Ludmila Belayev ◽  
Isabel Saul ◽  
Pil W Huh ◽  
Nicoletta Finotti ◽  
Weizhao Zhao ◽  
...  
Keyword(s):  
Brain Injury ◽  
Neuroprotective Effect ◽  
High Dose ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Albumin Therapy

scholarly journals Exogenous hydrogen sulfide attenuates cerebral ischemia–reperfusion injury by inhibiting autophagy in mice

2016 ◽  
Vol 94 (11) ◽  
pp. 1187-1192 ◽  
Author(s):  
Mengyang Shui ◽  
Xiaoyan Liu ◽  
Yuanjun Zhu ◽  
Yinye Wang
Keyword(s):  
Hydrogen Sulfide ◽  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Ischemic Injury ◽  
Artery Occlusion ◽  
Neurological Deficits ◽  
Western Blot Assay

Hydrogen sulfide (H2S), the third gas transmitter, has been proven to be neuroprotective in cerebral ischemic injury, but whether its effect is mediated by regulating autophagy is not yet clear. The present study was undertaken to explore the underlying mechanisms of exogenous H2S on autophagy regulation in cerebral ischemia. The effects and its connection with autophagy of NaHS, a H2S donor, were observed through neurological deficits and cerebral infarct volume in middle cerebral artery occlusion (MCAO) mice; autophagy-related proteins and autophagy complex levels in the ischemic hemisphere were detected with Western blot assay. Compared with the model group, NaHS significantly decreased infarct volume and improved neurological deficits; rapamycin, an autophagy activator, abolished the effect of NaHS; NaHS decreased the expression of LC3-II and up-regulated p62 expression in the ischemic cortex 24 h after ischemia. However, NaHS did not significantly influence Beclin-1 expression. H2S has a neuroprotective effect on ischemic injury in MCAO mice; this effect is associated with its influence in down-regulating autophagosome accumulation.

Sign in / Sign up

Export Citation Format

Share Document