Edaravone attenuates neuronal apoptosis in hypoxic-ischemic brain damage rat model via suppression of TRAIL signaling pathway

Abstract Lepidium meyenii (Maca) is an annual or biennial herb from South America that is a member of the genus Lepidium L. in the family Cruciferae. This herb has antioxidant, anti-apoptotic, and enhances autophagy functions and can prevent cell death, and protect neurons from ischemic damage. Macamide B, an effective active ingredient of maca, has a neuroprotective role in neonatal hypoxic-ischemic brain damage (HIBD), and the underlying mechanism of its neuroprotective effect is not yet known. The purpose of this study is to explore the impact of macamide B on HIBD-induced autophagy and apoptosis and its potential mechanism for neuroprotection. The modified Rice-Vannucci method was used to induce HIBD on 7-day-old (P7) macamide B and vehicle-pretreated pups. TTC staining was used to evaluate the cerebral infarct volume of pups, brain water content was measured to evaluate the neurological function of pups, neurobehavioral testing was used to assess functional recovery after HIBD, TUNEL and FJC staining was used to detect cell autophagy and apoptosis, and western blot analysis was used to detect the expression levels of the pro-survival signaling pathway phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and autophagy and the apoptosis-related proteins. The results show that macamide B pretreatment can significantly decrease brain damage, improve the recovery of neural function after HIBD. At the same time, macamide B pretreatment can induce the activation of PI3K/AKT signaling pathway after HIBD, enhance autophagy, and reduce hypoxic-ischemic (HI)-induced apoptosis. In addition, 3-methyladenine (3-MA), an inhibitor of PI3K/AKT signaling pathway, significantly inhibits the increase in autophagy levels, aggravates HI-induced apoptosis, and reverses the neuroprotective effect of macamide B on HIBD. Our data indicate that macamide B pretreatment might regulate autophagy through PI3K/AKT signaling pathway, thereby reducing HIBD-induced apoptosis and exerting neuroprotective effects on neonatal HIBD. Macamide B may become a new drug for the prevention and treatment of HIBD.

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Tanshinone IIa Alleviates the Biochemical Changes Associated with Hypoxic Ischemic Brain Damage in a Rat Model

Phytotherapy Research ◽

10.1002/ptr.3500 ◽

2011 ◽

Vol 25 (12) ◽

pp. 1865-1869 ◽

Cited By ~ 12

Author(s):

Mingyan Hei ◽

Yali Luo ◽

Xiaochun Zhang ◽

Furong Liu

Keyword(s):

Brain Damage ◽

Rat Model ◽

Biochemical Changes ◽

Tanshinone Iia ◽

Ischemic Brain Damage ◽

Ischemic Brain

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Effects of MicroRNA-592-5p on Hippocampal Neuron Injury Following Hypoxic-Ischemic Brain Damage in Neonatal Mice - Involvement of PGD2/DP and PTGDR

Cellular Physiology and Biochemistry ◽

10.1159/000486923 ◽

2018 ◽

Vol 45 (2) ◽

pp. 458-473 ◽

Cited By ~ 9

Author(s):

Li-Qun Sun ◽

Gong-Liang Guo ◽

Sai Zhang ◽

Li-Li Yang

Keyword(s):

Cell Cycle ◽

Mouse Model ◽

Signaling Pathway ◽

Brain Damage ◽

Target Gene ◽

Ischemic Brain Damage ◽

Ischemic Brain ◽

Expression Levels ◽

Neonatal Mice ◽

Group A

Background/Aims: This study aimed to explore the effect of microRNA-592-5p (miR-592-5p) on hypoxic-ischemic brain damage (HIBD)-induced hippocampal neuronal injury in a neonatal mouse model relative to the involvement of one target gene, PTGDR, and the PGD2/ DP signaling pathway. Methods: A total of 30 neonatal mice aged 7 days were randomly selected to establish an HIBD mouse model. Hippocampal neuronal cells were transfected into a control group, a blank group, a negative control (NC) group, an miR-592-5p mimics group, an miR-592-5p inhibitors group, an siRNA-PTGDR group and an miR-592-5p inhibitors + siRNA-PTGDR group. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analyses were performed to detect the expression levels of miR-592-5p, PTGDR, DP2, Bcl-2 and Bax in tissues and cells. Cell proliferation, cell cycle and apoptosis were detected by MTT assay and flow cytometry, respectively. Results: The expression levels of miR-592-5p and Bcl-2 decreased, while the expression levels of PTGDR, DP2 and Bax increased in the HIBD group. PTGDR is a target gene of miR-592-2p. Compared with the NC and blank groups, the expression levels of PTGDR, DP2 and Bax decreased, while the expression levels of miR-592-5p and Bcl-2 increased in the miR-592-5p mimics group. The siRNA-PTGDR group showed the same trend as that observed in the miR-592-5p mimics group, except with no difference in miR-592-5p expression. The miR-592-5p inhibitors group showed an opposite gene expression trend compared to that in the miR-592-5p mimics group. The S phase of the cell cycle was prolonged, the G1 phase was reduced, proliferation was increased, and the apoptosis rate was decreased in the siRNA-PTGDR and miR-592-5p mimics groups. Opposite trends for cell cycle, proliferation and apoptosis were observed in the miR-592-5p inhibitors group. Conclusions: Our study suggests that miR-592-5p upregulation protects against hippocampal neuronal injury caused by HIBD by targeting PTGDR and inhibiting the PGD2/DP signaling pathway.

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Melatonin alleviates brain and peripheral tissue edema in a neonatal rat model of hypoxic-ischemic brain damage: the involvement of edema related proteins

BMC Pediatrics ◽

10.1186/s12887-017-0824-x ◽

2017 ◽

Vol 17 (1) ◽

Cited By ~ 11

Author(s):

Li-Xiao Xu ◽

Yuan Lv ◽

Yan-Hong Li ◽

Xin Ding ◽

Ying Wang ◽

...

Keyword(s):

Brain Damage ◽

Rat Model ◽

Peripheral Tissue ◽

Neonatal Rat ◽

Ischemic Brain Damage ◽

Ischemic Brain ◽

Tissue Edema ◽

Related Proteins ◽

Neonatal Rat Model

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5-LOX Inhibitor Zileuton Reduces Inflammatory Reaction and Ischemic Brain Damage Through the Activation of PI3K/Akt Signaling Pathway

Neurochemical Research ◽

10.1007/s11064-016-1994-x ◽

2016 ◽

Vol 41 (10) ◽

pp. 2779-2787 ◽

Cited By ~ 19

Author(s):

Xian-kun Tu ◽

Hua-bin Zhang ◽

Song-sheng Shi ◽

Ri-sheng Liang ◽

Chun-hua Wang ◽

...

Keyword(s):

Signaling Pathway ◽

Brain Damage ◽

Inflammatory Reaction ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Ischemic Brain Damage ◽

Ischemic Brain

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Early TLR4 inhibition reduces hippocampal injury at puberty in a rat model of neonatal hypoxic-ischemic brain damage via regulation of neuroimmunity and synaptic plasticity

Experimental Neurology ◽

10.1016/j.expneurol.2019.113039 ◽

2019 ◽

Vol 321 ◽

pp. 113039 ◽

Cited By ~ 4

Author(s):

Zhen Tang ◽

Shaowu Cheng ◽

Yanyan Sun ◽

Yunqiao Zhang ◽

Xiying Xiang ◽

...

Keyword(s):

Synaptic Plasticity ◽

Brain Damage ◽

Rat Model ◽

Ischemic Brain Damage ◽

Ischemic Brain

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Significant Role of microRNA-182-5p in Neonatal Hypoxic-Ischemic Injury and Related Mechanism

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2020.2301 ◽

2020 ◽

Vol 10 (5) ◽

pp. 654-661

Author(s):

Qin Wang ◽

Ting Wang

Keyword(s):

Cell Viability ◽

Brain Tissue ◽

Brain Damage ◽

Rat Model ◽

Target Gene ◽

Luciferase Reporter ◽

Ischemic Brain Damage ◽

Ischemic Brain ◽

Qrt Pcr ◽

The Brain

The purpose of current study was to explore the role and mechanism of microRNA-182-5p (miR182-5p) in neonatal hypoxic ischemic brain damage (HIBD). First, we established a hypoxic-ischemic (HI) rat model and assessed the neurological function of the rats using the Zea Longa score. Then, the level of miR-182-5p in brain tissue of neonatal rats was determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Findings revealed that miR-182-5p was significantly down-regulated in the brain tissue of HI rat model. Next, we studied the target gene of miR-182-5p by using TargetScan and dual luciferase reporter assay. Results showed that CASP2 was a direct target gene of miR-182-5p, and the level of CASP2 was significantly up-regulated in the brain tissue of HI rat model. Immediately thereafter, we established an oxygen and glucose deprivation (OGD) cell model of primary cortical neurons, and demonstrated the changes of miR182-5p in cells treated with OGD by qRT-PCR. Finally, to determine the function of miR-182-5p in OGD subjected neuronal cells, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and flow cytometry (FCM) assays were used to study cell viability and apoptosis. The study found that compared with the OGD group, miR-182-5p mimic significantly increased nerve cell viability, reduced cell apoptosis and decreased cleaved-Caspase3/7/8 protein expression, however, all these changes were significantly reversed by overexpression of the CASP2 gene. Taken together, miR-182-5p might protect the nerve cells from ischemia and hypoxia by targeting CASP2, thereby playing a protective role in hypoxic ischemic encephalopathy, which might be a new effective target for neonatal hypoxic ischemic brain damage treatment.

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