Inhibition of leukotriene B4 synthesis protects against early brain injury possibly via reducing the neutrophil-generated inflammatory response and oxidative stress after subarachnoid hemorrhage in rats

2018 ◽  
Vol 339 ◽  
pp. 19-27 ◽  
Author(s):  
Zhen-Nan Ye ◽  
Ling-Yun Wu ◽  
Jing-Peng Liu ◽  
Qiang Chen ◽  
Xiang-Sheng Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Inflammatory Response ◽  
Early Brain Injury ◽  
Leukotriene B4 ◽  
And Oxidative Stress

scholarly journals Apelin-13/APJ system attenuates early brain injury via suppression of endoplasmic reticulum stress-associated TXNIP/NLRP3 inflammasome activation and oxidative stress in a AMPK-dependent manner after subarachnoid hemorrhage in rats

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Weilin Xu ◽  
Tao Li ◽  
Liansheng Gao ◽  
Jingwei Zheng ◽  
Jun Yan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Er Stress ◽  
Early Brain Injury ◽  
Inflammasome Activation ◽  
Dependent Manner ◽  
Neuroprotective Effects ◽  
And Oxidative Stress

Abstract Background Neuroinflammation and oxidative stress play important roles in early brain injury following subarachnoid hemorrhage (SAH). This study is the first to show that activation of apelin receptor (APJ) by apelin-13 could reduce endoplasmic reticulum (ER)-stress-associated inflammation and oxidative stress after SAH. Methods Apelin-13, apelin siRNA, APJ siRNA, and adenosine monophosphate-activated protein kinase (AMPK) inhibitor-dorsomorphin were used to investigate if the activation of APJ could provide neuroprotective effects after SAH. Brain water content, neurological functions, blood-brain barrier (BBB) integrity, and inflammatory molecules were evaluated at 24 h after SAH. Western blotting and immunofluorescence staining were applied to assess the expression of target proteins. Results The results showed that endogenous apelin, APJ, and p-AMPK levels were significantly increased and peaked in the brain 24 h after SAH. In addition, administration of exogenous apelin-13 significantly alleviated neurological functions, attenuated brain edema, preserved BBB integrity, and also improved long-term spatial learning and memory abilities after SAH. The underlying mechanism of the neuroprotective effects of apelin-13 is that it suppresses microglia activation, prevents ER stress from overactivation, and reduces the levels of thioredoxin-interacting protein (TXNIP), NOD-like receptor pyrin domain-containing 3 protein (NLRP3), Bip, cleaved caspase-1, IL-1β, TNFα, myeloperoxidase (MPO), and reactive oxygen species (ROS). Furthermore, the use of APJ siRNA and dorsomorphin abolished the neuroprotective effects of apelin-13 on neuroinflammation and oxidative stress. Conclusions Exogenous apelin-13 binding to APJ attenuates early brain injury by reducing ER stress-mediated oxidative stress and neuroinflammation, which is at least partly mediated by the AMPK/TXNIP/NLRP3 signaling pathway.

Dimethylfumarate alleviates early brain injury and secondary cognitive deficits after experimental subarachnoid hemorrhage via activation of Keap1-Nrf2-ARE system

2015 ◽  
Vol 123 (4) ◽  
pp. 915-923 ◽  
Author(s):  
Yizhi Liu ◽  
Jiaoxue Qiu ◽  
Zhong Wang ◽  
Wanchun You ◽  
Lingyun Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Inflammatory Response ◽  
Neuroprotective Effect ◽  
Autologous Blood ◽  
Early Brain Injury ◽  
Related Factor ◽  
Learning Deficits

OBJECT Oxidative stress and the inflammatory response are thought to promote brain damage in the setting of subarachnoid hemorrhage (SAH). Previous reports have shown that dimethylfumarate (DMF) can activate the Kelch-like ECH-associated protein 1–nuclear factor erythroid 2-related factor 2–antioxidant-responsive element (Keap1-Nrf2-ARE) system in vivo and in vitro, which leads to the downregulation of oxidative stress and inflammation. The aim of this study was to evaluate the potential neuroprotective effect of DMF on SAH-induced brain injury in rats. METHODS Rats were subjected to SAH by the injection of 300 μl of autologous blood into the chiasmatic cistern. Rats in a DMF-treated group were given 15 mg/kg DMF twice daily by oral gavage for 2 days after the onset of SAH. Cortical apoptosis, neural necrosis, brain edema, blood-brain barrier impairment, learning deficits, and changes in the Keap1-Nrf2-ARE pathway were assessed. RESULTS Administration of DMF significantly ameliorated the early brain injury and learning deficits induced by SAH in this animal model. Treatment with DMF markedly upregulated the expressions of agents related to Keap1-Nrf2-ARE signaling after SAH. The inflammatory response and oxidative stress were downregulated by DMF therapy. CONCLUSIONS DMF administration resulted in abatement of the development of early brain injury and cognitive dysfunction in this prechiasmatic cistern SAH model. This result was probably mediated by the effect of DMF on the Keap1-Nrf2-ARE system.

Apigenin attenuates oxidative stress and neuronal apoptosis in early brain injury following subarachnoid hemorrhage

2017 ◽  
Vol 40 ◽  
pp. 157-162 ◽  
Author(s):  
Yuwei Han ◽  
Tingting Zhang ◽  
Jingyuan Su ◽  
Yuan Zhao ◽  
Chenchen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Neuronal Apoptosis ◽  
Early Brain Injury

Amelioration of oxidative stress and protection against early brain injury by astaxanthin after experimental subarachnoid hemorrhage

2014 ◽  
Vol 121 (1) ◽  
pp. 42-54 ◽  
Author(s):  
Xiang-Sheng Zhang ◽  
Xin Zhang ◽  
Meng-Liang Zhou ◽  
Xiao-Ming Zhou ◽  
Ning Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Oral Administration ◽  
Brain Edema ◽  
Blood Brain Barrier ◽  
Early Brain Injury ◽  
Antioxidant Property ◽  
Neural Cell ◽  
Intracerebroventricular Injection

Object Aneurysmal subarachnoid hemorrhage (SAH) causes devastating rates of mortality and morbidity. Accumulating studies indicate that early brain injury (EBI) greatly contributes to poor outcomes after SAH and that oxidative stress plays an important role in the development of EBI following SAH. Astaxanthin (ATX), one of the most common carotenoids, has a powerful antioxidative property. However, the potential role of ATX in protecting against EBI after SAH remains obscure. The goal of this study was to assess whether ATX can attenuate SAH-induced brain edema, blood-brain barrier permeability, neural cell death, and neurological deficits, and to elucidate whether the mechanisms of ATX against EBI are related to its powerful antioxidant property. Methods Two experimental SAH models were established, including a prechiasmatic cistern SAH model in rats and a one-hemorrhage SAH model in rabbits. Both intracerebroventricular injection and oral administration of ATX were evaluated in this experiment. Posttreatment assessments included neurological scores, body weight loss, brain edema, Evans blue extravasation, Western blot analysis, histopathological study, and biochemical estimation. Results It was observed that an ATX intracerebroventricular injection 30 minutes post-SAH could significantly attenuate EBI (including brain edema, blood-brain barrier disruption, neural cell apoptosis, and neurological dysfunction) after SAH in rats. Meanwhile, delayed treatment with ATX 3 hours post-SAH by oral administration was also neuroprotective in both rats and rabbits. In addition, the authors found that ATX treatment could prevent oxidative damage and upregulate the endogenous antioxidant levels in the rat cerebral cortex following SAH. Conclusions These results suggest that ATX administration could alleviate EBI after SAH, potentially through its powerful antioxidant property. The authors conclude that ATX might be a promising therapeutic agent for EBI following SAH.

scholarly journals The Role of Oxidative Stress in Early Brain Injury after Subarachnoid Hemorrhage

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
M. Jelinek ◽  
M. Jurajda ◽  
K. Duris
Keyword(s):  
Oxidative Stress ◽  
Free Radicals ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Molecular Mechanisms ◽  
Early Brain Injury ◽  
Pathophysiological Mechanisms ◽  
Spontaneous Subarachnoid Hemorrhage ◽  
Antioxidant Mechanisms

This review focuses on the problem of oxidative stress in early brain injury (EBI) after spontaneous subarachnoid hemorrhage (SAH). EBI involves complex pathophysiological mechanisms, including oxidative stress. In the first section, we describe the main sources of free radicals in EBI. There are several sources of excessive generation of free radicals from mitochondrial free radicals’ generation and endoplasmic reticulum stress, to hemoglobin and enzymatic free radicals’ generation. The second part focuses on the disruption of antioxidant mechanisms in EBI. The third section describes some newly found molecular mechanisms and pathway involved in oxidative stress after EBI. The last section is dedicated to the pathophysiological mechanisms through which free radicals mediate early brain injury.

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