scholarly journals Lack of mitochondrial ferritin aggravated neurological deficits via enhancing oxidative stress in a traumatic brain injury murine model

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Ligang Wang ◽  
Libo Wang ◽  
Zhibo Dai ◽  
Pei Wu ◽  
Huaizhang Shi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Knockout Mice ◽  
Brain Injuries ◽  
Brain Infarction ◽  
Neurological Deficits ◽  
Important Correlation ◽  
The Brain ◽  
And Oxidative Stress

Oxidative stress has been strongly implicated in the pathogenesis of traumatic brain injury (TBI). Mitochondrial ferritin (Ftmt) is reported to be closely related to oxidative stress. However, whether Ftmt is involved in TBI-induced oxidative stress and neurological deficits remains unknown. In the present study, the controlled cortical impact model was established in wild-type and Ftmt knockout mice as a TBI model. The Ftmt expression, oxidative stress, neurological deficits, and brain injury were measured. We found that Ftmt expression was gradually decreased from 3 to 14 days post-TBI, while oxidative stress was gradually increased, as evidenced by reduced GSH and superoxide dismutase levels and elevated malondialdehyde and nitric oxide levels. Interestingly, the extent of reduced Ftmt expression in the brain was linearly correlated with oxidative stress. Knockout of Ftmt significantly exacerbated TBI-induced oxidative stress, intracerebral hemorrhage, brain infarction, edema, neurological severity score, memory impairment, and neurological deficits. However, all these effects in Ftmt knockout mice were markedly mitigated by pharmacological inhibition of oxidative stress using an antioxidant, N-acetylcysteine. Taken together, these results reveal an important correlation between Ftmt and oxidative stress after TBI. Ftmt deficiency aggravates TBI-induced brain injuries and neurological deficits, which at least partially through increasing oxidative stress levels. Our data suggest that Ftmt may be a promising molecular target for the treatment of TBI.

Protective effects of quercetin on traumatic brain injury induced inflammation and oxidative stress in cortex through activating Nrf2/HO-1 pathway

2021 ◽  
Vol 39 (1) ◽  
pp. 73-84
Author(s):  
Jianqiang Song ◽  
Guoliang Du ◽  
Haiyun Wu ◽  
Xiangliang Gao ◽  
Zhen Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Western Blot ◽  
Inflammatory Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Heme Oxygenase 1 ◽  
The Brain ◽  
And Oxidative Stress ◽  
Quercetin Treatment

Background: Traumatic brain injury (TBI) has been a serious public health issue. Clinically, there is an urgent need for agents to ameliorate the neuroinflammation and oxidative stress induced by TBI. Our previous research has demonstrated that quercetin could protect the neurological function. However, the detailed mechanism underlying this process remains poorly understood. Objective: This research was designed to investigate the mechanisms of quercetin to protect the cortical neurons. Methods: A modified weight-drop device was used for the TBI model. 5, 20 or 50 mg/kg quercetin was injected intraperitoneally to rats at 0.5, 12 and 24 h post TBI. Rats were sacrificed three days post injury and their cerebral cortex was obtained from the injured side. The rats were randomly assigned into three groups of equal number: TBI and quercetin group, TBI group, and Sham group. The brain water content was calculated to estimate the brain damage induced by TBI. Immunohistochemical and Western blot assays were utilized to investigate the neurobehavioral status. Enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction were performed to evaluate the inflammatory responses. The cortical oxidative stress was measured by estimating the activities of malondialdehyde, superoxide dismutase, catalase and glutathione-Px. Western blot was utilized to evaluate the expression of nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1). Results: Quercetin attenuated the brain edema and microgliosis in TBI rats. Quercetin treatment attenuated cortical inflammatory responses and oxidative stress induced by TBI insults. Quercetin treatment activated the cortical Nrf2/HO-1 pathway in TBI rats. Conclusions: Quercetin ameliorated the TBI-induced neuroinflammation and oxidative stress in the cortex through activating the Nrf2/HO-1 pathway.

Minocycline effects on cerebral edema: Relations with inflammatory and oxidative stress markers following traumatic brain injury in mice

2009 ◽  
Vol 1291 ◽  
pp. 122-132 ◽  
Author(s):  
Shadi Homsi ◽  
Fabiola Federico ◽  
Nicole Croci ◽  
Bruno Palmier ◽  
Michel Plotkine ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cerebral Edema ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
And Oxidative Stress

scholarly journals Annexin A2 Deficiency Exacerbates Neuroinflammation and Long-Term Neurological Deficits after Traumatic Brain Injury in Mice

2019 ◽  
Vol 20 (24) ◽  
pp. 6125 ◽  
Author(s):  
Ning Liu ◽  
Yinghua Jiang ◽  
Joon Yong Chung ◽  
Yadan Li ◽  
Zhanyang Yu ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Inflammatory Response ◽  
Neurovascular Unit ◽  
Annexin A2 ◽  
Tissue Loss ◽  
Neurological Deficits ◽  
Endogenous Factors ◽  
The Brain

Our laboratory and others previously showed that Annexin A2 knockout (A2KO) mice had impaired blood–brain barrier (BBB) development and elevated pro-inflammatory response in macrophages, implying that Annexin A2 (AnxA2) might be one of the key endogenous factors for maintaining homeostasis of the neurovascular unit in the brain. Traumatic brain injury (TBI) is an important cause of disability and mortality worldwide, and neurovascular inflammation plays an important role in the TBI pathophysiology. In the present study, we aimed to test the hypothesis that A2KO promotes pro-inflammatory response in the brain and worsens neurobehavioral outcomes after TBI. TBI was conducted by a controlled cortical impact (CCI) device in mice. Our experimental results showed AnxA2 expression was significantly up-regulated in response to TBI at day three post-TBI. We also found more production of pro-inflammatory cytokines in the A2KO mouse brain, while there was a significant increase of inflammatory adhesion molecules mRNA expression in isolated cerebral micro-vessels of A2KO mice compared with wild-type (WT) mice. Consistently, the A2KO mice brains had a significant increase in leukocyte brain infiltration at two days after TBI. Importantly, A2KO mice had significantly worse sensorimotor and cognitive function deficits up to 28 days after TBI and significantly larger brain tissue loss. Therefore, these results suggested that AnxA2 deficiency results in exacerbated early neurovascular pro-inflammation, which leads to a worse long-term neurologic outcome after TBI.

scholarly journals Treadmill Exercise Protects Against Pentylenetetrazol-Induced Seizures and Oxidative Stress after Traumatic Brain Injury

2013 ◽  
Vol 30 (14) ◽  
pp. 1278-1287 ◽  
Author(s):  
Luiz Fernando Almeida Silva ◽  
Maurício Scopel Hoffmann ◽  
Rogério da Rosa Gerbatin ◽  
Fernando da Silva Fiorin ◽  
Fernando Dobrachinski ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Treadmill Exercise ◽  
And Oxidative Stress

scholarly journals 17β-Estradiol Attenuates Intracerebral Hemorrhage-Induced Blood–Brain Barrier Injury and Oxidative Stress Through SRC3-Mediated PI3K/Akt Signaling Pathway in a Mouse Model

ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142110384
Author(s):  
Han Xiao ◽  
Jianyang Liu ◽  
Jialin He ◽  
Ziwei Lan ◽  
Mingyang Deng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Mouse Model ◽  
Intracerebral Hemorrhage ◽  
Signaling Pathway ◽  
Brain Edema ◽  
Akt Signaling ◽  
Neurological Deficits ◽  
Akt Signaling Pathway ◽  
And Oxidative Stress

Estrogen is neuroprotective in brain injury models, and steroid receptor cofactor 3 (SRC3) mediates estrogen signaling. We aimed to investigate whether and how SRC3 is involved in the neuroprotective effects of 17ß-estradiol (E2) in a mouse model of intracerebral hemorrhage (ICH). Ovariectomized female mice were treated with E2 after autologous blood injection-induced ICH. Brain damage was assessed by neurological deficit score, brain water content, and oxidative stress levels. Blood–brain barrier (BBB) integrity was evaluated by Evan's blue extravasation and claudin-5, ZO-1, and occludin levels. SRC3 expression and PI3K/Akt signaling pathway were examined in ICH mice treated with E2. The effect of SRC3 on E2-mediated neuroprotection was determined by examining neurological outcomes in SRC3-deficient mice undergone ICH and E2 treatment. We found that E2 alleviated ICH-induced brain edema and neurological deficits, protected BBB integrity, and suppressed oxidative stress. E2 enhanced SRC3 expression and PI3K-/Akt signaling pathway. SRC3 deficiency abolished the protective effects of E2 on ICH-induced neurological deficits, brain edema, and BBB integrity. Our results suggest that E2 suppresses ICH-induced brain injury and SRC3 plays a critical role in E2-mediated neuroprotection.

scholarly journals κ-Opioid Receptor Agonist Ameliorates Postoperative Neurocognitive Disorder by Activating the Ca2+/CaMKII/CREB Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Guopeng Ding ◽  
Dandan Li ◽  
Yingjie Sun ◽  
Keyan Chen ◽  
Dandan Song
Keyword(s):  
Oxidative Stress ◽  
Cardiopulmonary Bypass ◽  
Brain Injury ◽  
Opioid Receptor ◽  
Stress Factors ◽  
Neurocognitive Disorder ◽  
Apoptosis Rate ◽  
The Brain ◽  
And Oxidative Stress ◽  
Creb Pathway

Objective. Cardiopulmonary bypass (CPB) is an important cardiac operation and also a high-risk procedure, leading to postoperative neurocognitive disorder. However, there are few effective drugs to treat the aftermath of CPB. Therefore, we observe the effect of kappa opioid receptor (KOR) agonist on cognitive disorders of rats after cardiopulmonary bypass (CPB) and investigate the mechanism of the Ca2+/calmodulin-dependent protein kinase (CaMKII)/cAMP responsive element-binding protein (CREB) pathway. Methods. A total of 40 Sprague Dawley rats were randomly divided into the sham operation group (sham group, n = 10), CPB model group (CPB group, n = 10), CPB + KOR agonist U50488H group (UH group, n = 10), and CPB + specific CaMKII antagonist + U50488H group (CKU group, n = 10). The changes in the rats’ cognitive function were evaluated using the Morris water maze, the hippocampal histopathological changes were observed via hematoxylin-eosin (H&E) staining, and the apoptosis rate of neuronal cells was detected through terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. Moreover, enzyme-linked immunosorbent assay (ELISA) was applied to examine the changes in brain injury markers, inflammatory factors, and oxidative stress factors. The hippocampal variations in Ca2+ concentration and oxidative stress index (ROS) levels were measured by immunofluorescence staining, and western blotting was performed to determine the expression changes in the Ca2+/CaMKII/CREB pathway. Results. The KOR agonist could shorten latency, increase the swimming distance and residence time in the target quadrant, and ameliorate postoperative neurocognitive disorder (PND). Meanwhile, the KOR agonist relieved CPB-induced hippocampal and oxidative stress injuries, reduced NSE and S-100β expression, decreased the apoptosis rate, and repressed the inflammatory response, which alleviated the brain injury. In addition, U50488H was able to decrease Ca2+ influx and glutamate (Glu) level, inhibit N-methyl-D-aspartate receptor (NMDAR) expression, upregulate CaMKII expression, promote CREB phosphorylation, and increase the brain-derived neurotrophic factor (BDNF) level in CPB rats. However, the protective effects of KORs against PND were suppressed following the application of the CaMKII-specific antagonist. Conclusion. The KOR agonist activates the Ca2+/CaMKII/CREB pathway, which improves the brain injury and relieves PND in CPB rats.

scholarly journals Aucubin alleviates oxidative stress and inflammation via Nrf2-mediated signaling activity in experimental traumatic brain injury

2020 ◽  
Author(s):  
Han Wang ◽  
Xiaoming Zhou ◽  
Lingyun Wu ◽  
Guangjie Liu ◽  
Weidong Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cortical Neurons ◽  
Neurological Deficits ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tunel Staining ◽  
Related Factor ◽  
Mice Model ◽  
Anti Inflammatory

Abstract Background: Aucubin (Au) has anti-oxidative and anti-inflammatory bioactivities; however, its effects on a traumatic brain injury (TBI) model remain unknown. We explored the potential role of Au in a H2O2-induced oxidant damage in primary cortical neurons and weight-drop induced-TBI in a mouse model.Methods: Neuronal apoptosis, brain water content, histological damages and neurological deficits and cognitive functions were measured. We performed western blot, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, Nissl staining, quantitative real time polymerase chain reaction (q-PCR), immunofluorescence/immunohistochemistry and enzyme linked immunosorbent assay (ELISA). RNA interference experiments were performed to determine the effects of Nuclear factor erythroid-2 related factor 2 (Nrf2) on TBI mice with intraperitoneal injection of Au.Results: We found that Au enhanced the translocation of Nrf2 into the nucleus, activated antioxidant enzymes, suppressed excessive generation of reactive oxygen species (ROS) and reduced cell apoptosis in vitro and vivo experiments. In the mice model of TBI, Au markedly attenuated brain edema, histological damages and improved neurological and cognitive deficits. Au significantly suppressed high mobility group box 1(HMGB1)-mediated aseptic inflammation. Nrf2 knockdown in TBI mice blunted the antioxidant and anti-inflammatory neuroprotective effects of the Au.Conclusions: Taken together, our data suggest that Au provides a neuroprotective effect in TBI mice model by inhibiting oxidative stress and inflammatory responses; the mechanisms involve triggering Nrf2-induced antioxidant system.

scholarly journals Depleting SOX2 improves ischemic stroke via lncRNA PVT1/microRNA-24-3p/STAT3 axis

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Zhongjun Chen ◽  
Tieping Fan ◽  
Xusheng Zhao ◽  
Zhichen Zhang
Keyword(s):  
Oxidative Stress ◽  
Ischemic Stroke ◽  
Brain Injury ◽  
Water Content ◽  
Artery Occlusion ◽  
Neurological Deficits ◽  
Neuron Survival ◽  
Non Coding Rna ◽  
Cerebral Artery Occlusion ◽  
And Oxidative Stress

Abstract Objectives Studies have widely explored in the filed of ischemic stroke (IS) with their focus on transcription factors. However, few studies have pivoted on sex determining region Y-box 2 (SOX2) in IS. Thus, this study is launched to figure out the mechanisms of SOX2 in IS. Methods Rat middle cerebral artery occlusion (MCAO) was established as a stroke model. MCAO rats were injected with depleted SOX2 or long non-coding RNA plasmacytoma variant translocation 1 (PVT1) to explore their roles in neurological deficits, cerebral water content, neuron survival, apoptosis and oxidative stress. The relationship among SOX2, PVT1, microRNA (miR)-24-3p and signal transducer and activator of transcription 3 (STAT3) was verified by a series of experiments. Results SOX2, PVT1 and STAT3 were highly expressed while miR-24-3p was poorly expressed in cerebral cortex tissues of MCAO rats. Depleted SOX2 or PVT1 alleviated brain injury in MCAO rats as reflected by neuronal apoptosis and oxidative stress restriction, brain water content reduction, and neurological deficit and neuron survival improvements. Overexpression of PVT1 functioned oppositely. Restored miR-24-3p abolished PVT1 overexpression-induced brain injury in MCAO rats. SOX2 directly promoted PVT1 expression and further increased STAT3 by sponging miR-24-3p. Conclusion This study presents that depleting SOX2 improves IS via PVT1/miR-24-3p/STAT3 axis which may broaden our knowledge about the mechanisms of SOX2/PVT1/miR-24-3p/STAT3 axis and provide a reference of therapy for IS.

scholarly journals Intravenous Administration of Human Umbilical Cord Blood Reduces Neurological Deficit in the Rat after Traumatic Brain Injury

2002 ◽  
Vol 11 (3) ◽  
pp. 275-281 ◽  
Author(s):  
Dunyue Lu ◽  
Paul R. Sanberg ◽  
Asim Mahmood ◽  
Yi Li ◽  
Lei Wang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Neurological Deficits ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Vascular Walls ◽  
The Brain

We measured the effect of treatment of traumatic brain injury (TBI) in the rat with human umbilical cord blood (HUCB) administered IV. HUCB cells were injected into the tail vein 24 h after TBI and the rats were sacrificed at day 28 after the treatment. The Rotarod test and the neurological severity score (NSS) were used to evaluate neurological function. The distribution of the donor cells in the brain, heart, lung, kidney, liver, spleen, bone marrow, and muscle were analyzed in recipient rats using immunohistochemical staining and laser confocal microscopy. HUCB cells injected IV significantly reduced motor and neurological deficits compared with control groups by day 28 after the treatment. The cells preferentially entered the brain and migrated into the parenchyma of the injured brain and expressed the neuronal markers, NeuN and MAP-2, and the astrocytic marker, GFAP. Some HUCB cells integrated into the vascular walls within the boundary zone of the injured area. Our data suggest that IV administration of HUCB may be useful in the treatment of TBI.

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