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

2016 ◽  
Vol 41 (10) ◽  
pp. 2779-2787 ◽  
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

scholarly journals Macamide B Pretreatment Attenuates Neonatal Hypoxic-Ischemic Brain Damage of Mice Induced Apoptosis by Regulates Autophagy Via The PI3K/AKT Signaling Pathway

2021 ◽  
Author(s):  
Xiaoxia Yang ◽  
Mengxia Wang ◽  
Qian Zhou ◽  
Yanxian Bai ◽  
Jing Liu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Brain Damage ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Induced Apoptosis ◽  
The Impact

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.

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

2018 ◽  
Vol 45 (2) ◽  
pp. 458-473 ◽  
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.

Propofol Reduces Inflammatory Reaction and Ischemic Brain Damage in Cerebral Ischemia in Rats

2014 ◽  
Vol 39 (5) ◽  
pp. 793-799 ◽  
Author(s):  
Song-sheng Shi ◽  
Wei-zhong Yang ◽  
Ye Chen ◽  
Jian-ping Chen ◽  
Xian-kun Tu
Keyword(s):  
Cerebral Ischemia ◽  
Brain Damage ◽  
Inflammatory Reaction ◽  
Ischemic Brain Damage ◽  
Ischemic Brain

scholarly journals Melatonin Protects Against Ischemic Brain Injury by Modulating PI3K/AKT Signaling Pathway via Suppression of PTEN Activity

ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142110228
Author(s):  
Yuanyuan Ran ◽  
Lin Ye ◽  
Zitong Ding ◽  
Fuhai Gao ◽  
Shuiqing Yang ◽  
...  
Keyword(s):  
Brain Damage ◽  
Neuronal Cell ◽  
Akt Signaling ◽  
In Vivo Model ◽  
Neuronal Membrane ◽  
Melatonin Treatment ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Akt Phosphorylation ◽  
Akt Activation

Stroke is one of the leading causes of death and disability worldwide with limited therapeutic options. Melatonin can attenuate ischemic brain damage with improved functional outcomes. However, the cellular mechanisms of melatonin-driven neuroprotection against post-stroke neuronal death remain unknown. Here, distal middle cerebral artery occlusion (dMCAO) was performed in C57BL/6j mice to develop an ischemic stroke in vivo model. Melatonin was injected intraperitoneally immediately after ischemia, and 24 and 48 hours later. Melatonin treatment, with 5 to 20 mg/kg, elicited a dose-dependent decrease in infarct volume and concomitant increase in sensorimotor function. At the molecular level, phosphorylation of PTEN and Akt were increased, whereas PTEN activity was decreased in melatonin treated animals 72 hours after dMCAO. At the cellular level, oxygenglucose deprivation (OGD) challenge of neuronal cell line Neuro-2a (N2a) and primary neurons supported melatonin’s direct protection against neuronal cell death. Melatonin treatment reduced LDH release and neuronal apoptosis at various time points, markedly increased Akt phosphorylation in neuronal membrane, but significantly suppressed it in the cytoplasm of post-OGD neurons. Mechanistically, melatonin-induced Akt phosphorylation and neuronal survival was blocked by Wortmannin, a potent PIP3 inhibitor, exposing increased PI3K/Akt activation as a central player in melatonin-driven neuroprotection. Finally, PTEN knock-down through siRNA significantly inhibited PI3K/Akt activation and cell survival following melatonin treatment, suggesting that melatonin protection against ischemic brain damage, is at least partially, dependent on modulation of the PTEN/PI3K/Akt signaling axis.

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