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 Sodium/Hydrogen Exchanger 1 Participates in Early Brain Injury after Subarachnoid Hemorrhage both in vivo and in vitro via Promoting Neuronal Apoptosis

2019 ◽  
Vol 28 (8) ◽  
pp. 985-1001 ◽  
Author(s):  
Huangcheng Song ◽  
Shuai Yuan ◽  
Zhuwei Zhang ◽  
Juyi Zhang ◽  
Peng Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Brain Edema ◽  
Neuronal Apoptosis ◽  
Early Brain Injury ◽  
Sodium Hydrogen ◽  
Sodium Hydrogen Exchanger

Sodium/hydrogen exchanger 1 (NHE1) plays an essential role in maintaining intracellular pH (pHi) homeostasis in the central nervous system (CNS) under physiological conditions, and it is also associated with neuronal death and intracellular Na+ and Ca2+ overload induced by cerebral ischemia. However, its roles and underlying mechanisms in early brain injury (EBI) induced by subarachnoid hemorrhage (SAH) have not been fully explored. In this research, a SAH model in adult male rat was established through injecting autologous arterial blood into prechiasmatic cistern. Meanwhile, primary cultured cortical neurons of rat treated with 5 μM oxygen hemoglobin (OxyHb) for 24 h were applied to mimic SAH in vitro. We find that the protein levels of NHE1 are significantly increased in brain tissues of rats after SAH. Downregulation of NHE1 by HOE642 (a specific chemical inhibitor of NHE1) and genetic-knockdown can effectively alleviate behavioral and cognitive dysfunction, brain edema, blood-brain barrier (BBB) injury, inflammatory reactions, oxidative stress, neurondegeneration, and neuronal apoptosis, all of which are involved in EBI following SAH. However, upregulation of NHE1 by genetic-overexpression can produce opposite effects. Additionally, inhibiting NHE1 significantly attenuates OxyHb-induced neuronal apoptosis in vitro and reduces interaction of NHE1 and CHP1 both in vivo and in vitro. Collectively, we can conclude that NHE1 participates in EBI induced by SAH through mediating inflammation, oxidative stress, behavioral and cognitive dysfunction, BBB injury, brain edema, and promoting neuronal degeneration and apoptosis.

scholarly journals Hyperbaric Oxygen Intervention Modulates Early Brain Injury after Experimental Subarachnoid Hemorrhage in Rats: Possible Involvement of TLR4/NF-κ B-Mediated Signaling Pathway

2016 ◽  
Vol 38 (6) ◽  
pp. 2323-2336 ◽  
Author(s):  
Hao Liu ◽  
Ming Yang ◽  
Li Pan ◽  
Peng Liu ◽  
Lianting Ma
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Signaling Pathway ◽  
Brain Edema ◽  
Blood Brain Barrier ◽  
Hyperbaric Oxygen ◽  
Early Brain Injury ◽  
Brain Barrier ◽  
Enzyme Linked Immunosorbent Assay ◽  
Blood Brain

Background/Aims: Previous studies have proved that the activation of TLR4/NF-κ B signaling pathway is involved in inflammatory processes in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Hyperbaric oxygen (HBO) intervention has successfully been used to treat several animal models of tissue injury via its anti-inflammation property. This study was undertaken to investigate the influence of HBO administration on the TLR4/NF-κ B signaling pathway in rats at the early stage of SAH. Methods: Male Sprague-Dawley rats (n = 150) were randomly divided into 5 groups: the sham, the sham + 2.8 atmospheres absolute (ATA) HBO group, the SAH group, the SAH + 2.0ATA HBO group, the SAH + 2.8ATA HBO group. Each group (n = 30) was randomly subdivided into three subgroups that were examined at the following time points: 24 h, 48 h and 72 h post-injury. HBO (100% O2, 2.0ATA or 2.8ATA for 90mins) was initiated 12 h after injury. Neurological deficit, brain edema and blood-brain barrier (BBB) permeability were assessed to evaluate the development of EBI. The expressions of TLR4, NF-κ B and pro-inflammatory cytokines in the cortical were determined by real time polymerase chain reaction (RT-PCR), western blot, immunohistochemistry, or enzyme-linked immunosorbent assay (ELISA). Results: Our study showed that treatment with HBO significantly decreased the expressions of TLR4, NF-κ B and the downstream inflammatory agents, such as TNF-α, IL-6, IL-1β and ICAM-1, and also improved brain edema, blood-brain barrier permeability and neurologic function. Conclusions: These findings indicate that HBO treatment may result in abatement of the development of EBI after SAH, possibly through suppression of TLR4/NF-κ B signaling pathway.

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

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.

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.

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