Neuroprotective Effects of Valproic Acid on Blood-Brain Barrier Disruption and Apoptosis-Related Early Brain Injury in Rats Subjected to Subarachnoid Hemorrhage Are Modulated by Heat Shock Protein 70/Matrix Metalloproteinases and Heat Shock Protein 70/AKT Pathways

Ying, Guangyu; Jing, Chaohui; Li, Jianru; Wu, Cheng Hsien; Yan, Feng; Chen, Jing-yin; Wang, Lin; Dixon, Brandon; Chen, Gao

doi:10.1227/neu.0000000000001264

Cited by 43 publications

(30 citation statements)

References 42 publications

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“…Consistent with this data, brain levels of HSP-70 were elevated after exposure to ZnONPs for 7 days as a consequence of the triggered oxidative stress and inflammation. In addition, it is demonstrated that HSP-70 is an inhibitor of apoptosis via inactivating caspase-3, and therefore could be cytoprotective [ 79 , 80 , 81 ]. The anti-apoptotic properties of HSP-70 have been attributed to its anti-oxidative action [ 82 , 83 ].…”

Section: Discussionmentioning

confidence: 99%

Zinc Oxide Nanoparticles Induced Oxidative DNA Damage, Inflammation and Apoptosis in Rat’s Brain after Oral Exposure

Attia

Nounou

Shalaby

2018

Toxics

112

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Growing evidences demonstrated that zinc oxide nanoparticles (ZnONPs) could reach the brain after oral ingestion; however, the “neurotoxicity of” ZnONPs after oral exposure has not been fully investigated. This study aimed to explore the “neurotoxicity of” ZnONPs (<100 nm) after oral exposure to two doses; 40 and 100 mg/kg for 24 h and 7 days. The exposure to 40 and 100 mg/kg of ZnONPs for 24 h did not elicit “neurotoxicity” compared to normal control. However, the daily exposure to both doses for 7 days caused oxidative stress in brain tissue as detected by the elevation of the levels of malondialdehyde, the main product of lipid peroxidation and nitrite as an index of nitric oxide with concomitant decline in the concentrations of antioxidants. In addition, both doses resulted in DNA fragmentation which was confirmed by increased percentage of tailed DNA, DNA tail intensity and length and tail moment particularly with the dose 100 mg/kg. Moreover, both doses led to the elevation of the inflammatory cytokines along with increased apoptotic markers including caspase-3 and Fas. Heat shock protein-70 levels were also elevated possibly as a compensatory mechanism to counteract the ZnONPs-induced oxidative stress and apoptosis. The present results indicate the “neurotoxicity of” ZnONPs after recurrent oral exposure via oxidative stress, genotoxicity, inflammatory response and apoptosis.

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Section: Discussionmentioning

confidence: 99%

Zinc Oxide Nanoparticles Induced Oxidative DNA Damage, Inflammation and Apoptosis in Rat’s Brain after Oral Exposure

Attia

Nounou

Shalaby

2018

Toxics

112

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“…The sections were incubated overnight at 4°C with primary antibodies, including antibodies against NeuN (Abcam, ab177487 or ab104224) and LC3 (Cell Signaling Technology, CST#4108) followed by the appropriate fluorophore-conjugated secondary antibodies (Jackson ImmunoResearch, West Grove, PA, USA). TUNEL staining was performed according to the protocol from the manufacturer (Roche Inc., Switzerland) as described in previous studies (Ying et al, 2016 ). The sections were visualized with a fluorescence microscope (LSM-710; Zeiss, Oberkochen, Germany).…”

Section: Methodsmentioning

confidence: 99%

Melatonin Regulates Apoptosis and Autophagy Via ROS-MST1 Pathway in Subarachnoid Hemorrhage

Shi

Liang

Zheng

et al. 2018

Front. Mol. Neurosci.

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Compelling evidence has indicated that imbalance between apoptosis and autophagy may be involved in subarachnoid hemorrhage (SAH). We aimed to investigate the effects and mechanisms of melatonin in the homeostasis of apoptosis and autophagy. One-hundred and forty-eight male Sprague-Dawley rats were intraperitoneally injected with melatonin or vehicle 2 h after SAH induction. Western blotting and an immunofluorescent assay were performed to detect the expression of apoptosis- and autophagy-related proteins. The neuroprotective effect of melatonin attenuating SAH-induced neurological deficit and brain edema may be associated with the suppression of SAH-induced neuronal apoptosis and autophagy. Furthermore, melatonin inhibited the cleavage of mammalian sterile 20-like kinase 1 (MST1) protein by reducing reactive oxygen species (ROS) content. These effects of melatonin on regulating the homeostasis between apoptosis and autophagy could be reversed by an MST1 agonist, chelerythrine, via enhancement of MST1 cleavage. In conclusion, exogenous melatonin alleviates SAH-induced early brain injury (EBI) by suppressing excessive neuronal apoptosis and autophagy. The underlying mechanism may, at least in part, involve the ROS-MST1 pathway.

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“…Propidium iodide (PI; sigma) was dissolved in 0.9% NaCl, and 10 mg/kg PI was administered intraperitoneally at 1 h prior to sacrifice. Brain coronal slices were obtained according to our previous protocol [ 23 ]. The slices were incubated at 4 °C over night with mouse monoclonal anti-neuronal nuclei (NeuN) (1:200, MAB377, Millipore), goat polyclonal anti-caspase-1 (1:200, sc-22165, Santa Cruz), and rabbit monoclonal anti-LC3 (1:200, 3868#, Cell signaling Technology) followed by incubation with appropriate secondary antibody (1:200, Jackson ImmunoResearch).…”

Section: Methodsmentioning

confidence: 99%

Fluoxetine-enhanced autophagy ameliorates early brain injury via inhibition of NLRP3 inflammasome activation following subarachnoid hemorrhage in rats

Nie

et al. 2017

J Neuroinflammation

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BackgroundThe NLRP3 inflammasome is a multiprotein complex that regulates the innate immune inflammatory response by activating caspase-1 and subsequent IL-1β and IL-18. Fluoxetine has been shown to have the anti-inflammatory properties in many disease models. However, the effects and mechanisms of these effects of fluoxetine in early brain injury after subarachnoid hemorrhage (SAH) have not been defined.MethodsThe SAH model was induced by an endovascular perforation in adult male Sprague-Dawley (SD) rats weighing 300–320 g. N-Ac-Tyr-Val-Ala-Asp-chloromethyl ketone (AC-YVAD-CMK) was injected intraperitoneally (5 mg/kg) 1 h after SAH. Fluoxetine was administered via intravenous route 6 h after SAH. 3-Methyladenine (3-MA) was intracerebroventricularly injected 20 min before SAH. SAH grade, neurological function, brain water content, propidium iodide (PI) staining, western blot, double immunostaining, and transmission electron microscopy were performed.ResultsExpression of caspase-1 increased and peaked at 24 h after SAH. Caspase activation was along with the increased necrotic cells, which occurred mainly in neurons. Necrotic cell death of microglia and astrocyte were also found. Administration of AC-YVAD-CMK, a caspase-1 inhibitor, reduced the expression of IL-1β and IL-18 and the number of PI-positive cells, attenuated brain edema, and improved neurological function, which was also observed in fluoxetine-treated rats. Furthermore, fluoxetine treatment significantly decreased the expression of NLRP3 and cleaved caspase-1 and upregulated the expression of beclin-1, a marker for autophagy. Finally, the effects of fluoxetine in NLRP3 inflammasome activation were reversed by additional 3-MA administration.ConclusionsTogether, our present study indicated that NLRP3 inflammasome and caspase-1 activation play a deleterious role in early brain injury and fluoxetine mitigates NLRP3 inflammasome and caspase-1 activation through autophagy activation after SAH, providing a potential therapeutic agent for SAH treatment.Electronic supplementary materialThe online version of this article (10.1186/s12974-017-0959-6) contains supplementary material, which is available to authorized users.

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Neuroprotective Effects of Valproic Acid on Blood-Brain Barrier Disruption and Apoptosis-Related Early Brain Injury in Rats Subjected to Subarachnoid Hemorrhage Are Modulated by Heat Shock Protein 70/Matrix Metalloproteinases and Heat Shock Protein 70/AKT Pathways

Abstract: BBB, blood-brain barrierEBI, early brain injuryHSP, heat shock proteinMMP, matrix metalloproteinasePBS, phosphate-buffered salineSAH, subarachnoid hemorrhageTUNEL, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelingVPA, valproic acid.

Cited by 43 publications

References 42 publications

Zinc Oxide Nanoparticles Induced Oxidative DNA Damage, Inflammation and Apoptosis in Rat’s Brain after Oral Exposure

Zinc Oxide Nanoparticles Induced Oxidative DNA Damage, Inflammation and Apoptosis in Rat’s Brain after Oral Exposure

Melatonin Regulates Apoptosis and Autophagy Via ROS-MST1 Pathway in Subarachnoid Hemorrhage

Fluoxetine-enhanced autophagy ameliorates early brain injury via inhibition of NLRP3 inflammasome activation following subarachnoid hemorrhage in rats

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