The interplay of microRNAs and post-ischemic glutamate excitotoxicity: an emergent research field in stroke medicine

Majdi, Alireza; Mahmoudi, Javad; Sadigh-Eteghad, Saeed; Farhoudi, Mehdi; Shotorbani, Siamak Sandoghchian

doi:10.1007/s10072-016-2643-5

Cited by 30 publications

(19 citation statements)

References 79 publications

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“…In recent years, growing evidence has suggested that microRNAs (miRNAs) play critical roles in ischemic stroke [11]. Experimental therapeutic approaches based on miRNAs have been developed to help post-stroke neurological recovery and ameliorate ischemic brain injury [12,13]. miR-29b-3p, one of the members of the miR-29b family to be identified, exhibits therapeutic potential for treating cardiometabolic disorders [14].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE:Bone mesenchymal stem cell-derived exosomal microRNA-29b-3p prevents hypoxic-ischemic injury in rat brain by activating the PTEN-mediated Akt signaling pathway

Hou¹,

Li²,

Zhao³

et al. 2020

J Neuroinflammation

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Background: Mesenchymal stem cells (MSCs) are suspected to exert neuroprotective effects in brain injury, in part through the secretion of extracellular vesicles like exosomes containing bioactive compounds. We now investigate the mechanism by which bone marrow MSCs (BMSCs)-derived exosomes harboring the small non-coding RNA miR-29b-3p protect against hypoxic-ischemic brain injury in rats. Methods:We established a rat model of middle cerebral artery occlusion (MCAO) and primary cortical neuron or brain microvascular endothelial cell (BMEC) models of oxygen and glucose deprivation (OGD). Exosomes were isolated from the culture medium of BMSCs. We treated the MCAO rats with BMSC-derived exosomes in vivo, and likewise the OGD-treated neurons and BMECs in vitro. We then measured apoptosis-and angiogenesis-related features using TUNEL and CD31 immunohistochemical staining and in vitro Matrigel angiogenesis assays. Results: The dual luciferase reporter gene assay showed that miR-29b-3p targeted the protein phosphatase and tensin homolog (PTEN). miR-29b-3p was downregulated and PTEN was upregulated in the brain of MCAO rats and in OGD-treated cultured neurons. MCAO rats and OGD-treated neurons showed promoted apoptosis and decreased angiogenesis, but overexpression of miR-29b-3p or silencing of PTEN could reverse these alterations. Furthermore, miR-29b-3p could negatively regulate PTEN and activate the Akt signaling pathway. BMSCs-derived exosomes also exerted protective effects against apoptosis of OGD neurons and cell apoptosis in the brain samples from MCAO rats, where we also observed promotion of angiogenesis.Conclusion: BMSC-derived exosomal miR-29b-3p ameliorates ischemic brain injury by promoting angiogenesis and suppressing neuronal apoptosis, a finding which may be of great significance in the treatment of hypoxic-ischemic brain injury.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE:Bone mesenchymal stem cell-derived exosomal microRNA-29b-3p prevents hypoxic-ischemic injury in rat brain by activating the PTEN-mediated Akt signaling pathway

Hou¹,

Li²,

Zhao³

et al. 2020

J Neuroinflammation

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“…Intriguingly, in nonischemic animals, DIM upregulated the expression of miR-223-3p involved in Grin2b degradation as well as increased methylation of Grin2b gene which links DIM to the control of excitotoxicity [41]. Moreover, in nonischemic rats, DIM stimulated expression of miRNAs such as miR-124, miR-384, and miR-181b, which are related to apoptosis, autophagy and/or excitotoxicity [42,43]. Similarly, re-expression of miRNAs in response to DIM was demonstrated in cancer cell lines [44].…”

Section: Discussionmentioning

confidence: 97%

Neuroprotective effect of 3,3’-Diindolylmethane against perinatal asphyxia involves inhibition of the AhR and NMDA signaling and hypermethylation of specific genes

et al. 2020

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Each year, 1 million children die due to perinatal asphyxia; however, there are no effective drugs to protect the neonatal brain against hypoxic/ischemic damage. In this study, we demonstrated for the first time the neuroprotective capacity of 3,3’-diindolylmethane (DIM) in an in vivo model of rat perinatal asphyxia, which has translational value and corresponds to hypoxic/ischemic episodes in human newborns. Posttreatment with DIM restored the weight of the ipsilateral hemisphere and normalized cell number in the brain structures of rats exposed to perinatal asphyxia. DIM also downregulated the mRNA expression of HIF1A-regulated Bnip3 and Hif1a which is a hypoxic marker, and the expression of miR-181b which is an indicator of perinatal asphyxia. In addition, DIM inhibited apoptosis and oxidative stress accompanying perinatal asphyxia through: downregulation of FAS, CASP-3, CAPN1, GPx3 and SOD-1, attenuation of caspase-9 activity, and upregulation of anti-apoptotic Bcl2 mRNA. The protective effects of DIM were accompanied by the inhibition of the AhR and NMDA signaling pathways, as indicated by the reduced expression levels of AhR, ARNT, CYP1A1, GluN1 and GluN2B, which was correlated with enhanced global DNA methylation and the methylation of the Ahr and Grin2b genes. Because our study provided evidence that in rat brain undergoing perinatal asphyxia, DIM predominantly targets AhR and NMDA, we postulate that compounds that possess the ability to inhibit their signaling are promising therapeutic tools to prevent stroke.

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“…By being the second most frequent mortality cause and also the first leading cause of adult disabilities, stroke is taking its toll in all over the world. 1 In tandem with its global trend, the stroke prevalence was demonstrated to be very high in Iran by involving approximately 139 per 100 000 cases in 2006. 2 The main mechanisms are disruption of cerebral blood flow and hypo-oxygenation, by which brain tissue is affected during an ischemic attack.…”

Section: Introductionmentioning

confidence: 99%

Effect of Whey Protein Supplementation on Inflammatory and Antioxidant Markers, and Clinical Prognosis in Acute Ischemic Stroke (TNS Trial): A Randomized, Double Blind, Controlled, Clinical Trial

et al. 2019

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Purpose: Malnutrition is extensively prevalent amongst critically ill patients afflicted by ischemic stroke (IS). This study purpose was to evaluate the protein whey effect on inflammatory and antioxidant markers and functional prognosis in acute IS patients. Methods: out of 42 patients with acute IS who were referred to Imam Reza Educational Hospital, Tabriz, Iran, 40 patients participated in the study. Twenty-one patients as control group received the hospital routine formula, and 19 patients as intervention group received 20 g/daily of whey protein through oral gavage. Inflammation and oxidative stress indicators (e.g., albumin, malondialdehyde (MDA), total antioxidant capacity (TAC), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and high sensitivity C reactive protein (hs-CRP)and clinical variables included in were evaluated using National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) during admission and also 3 weeks after intervention. Results: Whey protein supplementation significantly decreased the NIHSS and mRS scores, TNF-α, IL-6, and hs-CRP by passing 3 weeks from intervention (P<0.05). However, whey formula had no significant effect on other markers including albumin, and MDA. The hs-CRP (P = 0.02) reduction was significantly higher in whey protein group in comparison with control group. Conclusion: Whey protein supplementation reduced inflammation markers in those patients with IS. However, these changes should be studied in larger-scale trials.

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The interplay of microRNAs and post-ischemic glutamate excitotoxicity: an emergent research field in stroke medicine

Cited by 30 publications

References 79 publications

RETRACTED ARTICLE:Bone mesenchymal stem cell-derived exosomal microRNA-29b-3p prevents hypoxic-ischemic injury in rat brain by activating the PTEN-mediated Akt signaling pathway

RETRACTED ARTICLE:Bone mesenchymal stem cell-derived exosomal microRNA-29b-3p prevents hypoxic-ischemic injury in rat brain by activating the PTEN-mediated Akt signaling pathway

Neuroprotective effect of 3,3’-Diindolylmethane against perinatal asphyxia involves inhibition of the AhR and NMDA signaling and hypermethylation of specific genes

Effect of Whey Protein Supplementation on Inflammatory and Antioxidant Markers, and Clinical Prognosis in Acute Ischemic Stroke (TNS Trial): A Randomized, Double Blind, Controlled, Clinical Trial

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