scholarly journals Oxidative Stress in Intracerebral Hemorrhage: Sources, Mechanisms, and Therapeutic Targets

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Xin Hu ◽  
Chuanyuan Tao ◽  
Qi Gan ◽  
Jun Zheng ◽  
Hao Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Brain Damage ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Heme Iron ◽  
Mortality And Morbidity ◽  
Underlying Mechanisms ◽  
Damaging Effects

Intracerebral hemorrhage (ICH) is associated with the highest mortality and morbidity despite only constituting approximately 10–15% of all strokes. Complex underlying mechanisms consisting of cytotoxic, excitotoxic, and inflammatory effects of intraparenchymal blood are responsible for its highly damaging effects. Oxidative stress (OS) also plays an important role in brain injury after ICH but attracts less attention than other factors. Increasing evidence has demonstrated that the metabolite axis of hemoglobin-heme-iron is the key contributor to oxidative brain damage after ICH, although other factors, such as neuroinflammation and prooxidases, are involved. This review will discuss the sources, possible molecular mechanisms, and potential therapeutic targets of OS in ICH.

Oxidative Stress: Major Threat in Traumatic Brain Injury

2018 ◽  
Vol 17 (9) ◽  
pp. 689-695 ◽  
Author(s):  
Nidhi Khatri ◽  
Manisha Thakur ◽  
Vikas Pareek ◽  
Sandeep Kumar ◽  
Sunil Sharma ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mitochondrial Dysfunction ◽  
Calcium Influx ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Physical Assault ◽  
Mortality And Morbidity ◽  
Primary Injury

Background & Objective: Traumatic Brain Injury (TBI) is one of the major causes of mortality and morbidity worldwide. It represents mild, moderate and severe effects of physical assault to brain which may cause sequential, primary or secondary ramifications. Primary injury can be due to the first physical hit, blow or jolt to one of the brain compartments. The primary injury is then followed by secondary injury which leads to biochemical, cellular, and physiological changes like blood brain barrier disruption, inflammation, excitotoxicity, necrosis, apoptosis, mitochondrial dysfunction and generation of oxidative stress. Apart from this, there is also an immediate increase in glutamate at the synapses following severe TBI. Excessive glutamate at synapses in turn activates corresponding NMDA and AMPA receptors that facilitate excessive calcium influx into the neuronal cells. This leads to the generation of oxidative stress which further leads to mitochondrial dysfunction, lipid peroxidation and oxidation of proteins and DNA. As a consequence, neuronal cell death takes place and ultimately people start facing some serious disabilies. Conclusion: In the present review we provide extensive overview of the role of reactive oxygen species (ROS)-induced oxidative stress and its fatal effects on brain after TBI.

Novel Synthetic and Natural Therapies for Traumatic Brain Injury

2021 ◽  
Vol 19 ◽  
Author(s):  
Denise Battaglini ◽  
Dorota Siwicka-Gieroba ◽  
Patricia RM Rocco ◽  
Fernanda Ferreira Cruz ◽  
Pedro Leme Silva ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Damage ◽  
Molecular Mechanisms ◽  
Antioxidant Properties ◽  
Secondary Brain Injury ◽  
Specific Recommendation ◽  
Novel Therapies ◽  
Secondary Brain Damage ◽  
Late Treatment

: Traumatic brain injury (TBI) is a major cause of disability and death worldwide. The initial mechanical insult results in tissue and vascular disruption with hemorrhages and cellular necrosis that is followed by a dynamic secondary brain damage that presumably results in additional destruction of the brain. In order to minimize deleterious consequences of the secondary brain damage-such as inflammation, bleeding or reduced oxygen supply. The old concept of the -staircase approach- has been updated in recent years by most guidelines and should be followed as it is considered the only validated approach for the treatment of TBI. Besides, a variety of novel therapies have been proposed as neuroprotectants. The molecular mechanisms of each drug involved in inhibition of secondary brain injury can result as potential target for the early and late treatment of TBI. However, no specific recommendation is available on their use in clinical setting. The administration of both synthetic and natural compounds, which act on specific pathways involved in the destructive processes after TBI, even if usually employed for the treatment of other diseases, can show potential benefits. This review represents a massive effort towards current and novel therapies for TBI that have been investigated in both pre-clinical and clinical settings. This review aims to summarize the advancement in therapeutic strategies basing on specific and distinct -target of therapies-: brain edema, ICP control, neuronal activity and plasticity, anti-inflammatory and immunomodulatory effects, cerebral autoregulation, antioxidant properties, and future perspectives with the adoption of mesenchymal stromal cells.

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 Tandem Mass Tag-Based Quantitative Proteomic Analysis Reveals Pathways Involved in Brain Injury Induced by Chest Exposure to Shock Waves

2021 ◽  
Vol 14 ◽  
Author(s):  
Changci Tong ◽  
Peifang Cong ◽  
Ying Liu ◽  
Xiuyun Shi ◽  
Lin Shi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Signaling Pathways ◽  
Brain Damage ◽  
Western Blotting ◽  
Differentially Expressed ◽  
Tandem Mass ◽  
Differentially Expressed Proteins ◽  
Blast Exposure ◽  
Tandem Mass Tag

Recurrent chest blast exposure can lead to brain inflammation, oxidative stress, and mental disorders in soldiers. However, the mechanism that underlies brain injury caused indirectly by chest blasts remains unclear. It is urgent to find additional reliable biomarkers to reveal the intimate details of the pathogenesis of this phenomenon. We used the term tandem mass tag (TMT) labeling combined with liquid chromatography–tandem mass spectrometry (LC-MS/MS) to screen for differentially expressed proteins in rat brain at different time points after a chest blast. Data are available via ProteomeXchange with the identifier PXD025204. Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), the Database for Annotation, Visualization and Integrated Discovery (DAVID), and Cytoscape analyses were used to analyze the proteomic profiles of blast-exposed rats. In addition, we performed Western blotting to verify protein levels. We identified 6,931 proteins, of which 255 were differentially expressed and 43, 84, 52, 97, and 49 were identified in brain tissues at 12, 24, 48, and 72 h and 1 week after chest blast exposure, respectively. In this study, the GO, KEGG, Clusters of Orthologous Groups of proteins, and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) analyses indicated that brain damage caused by chest blast exposure involved many important biological processes and signaling pathways, such as inflammation, cell adhesion, phagocytosis, neuronal and synaptic damage, oxidative stress, and apoptosis. Furthermore, Western blotting confirmed that these differentially expressed proteins and affected signaling pathways were associated with brain damage caused by chest blast exposure. This study identifies potential protein biomarkers of brain damage caused indirectly by chest blast and new targets for the treatment of this condition.

scholarly journals The Influence of Oxidative Stress on Neurological Outcomes in Spontaneous Intracerebral Hemorrhage

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1615
Author(s):  
Julia Masomi-Bornwasser ◽  
Elena Kurz ◽  
Christina Frenz ◽  
Jan Schmitt ◽  
Dominik M. A. Wesp ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Total Antioxidant Status ◽  
Secondary Brain Injury ◽  
Spontaneous Intracerebral Hemorrhage ◽  
Neurological Outcomes ◽  
Total Antioxidant ◽  
Patient’S Outcome ◽  
The Impact

Spontaneous intracerebral hemorrhage (ICH) causes, besides the primary brain injury, a secondary brain injury (SBI), which is induced, amongst other things, by oxidative stress (OS) and inflammation, determining the patient’s outcome. This study aims to assess the impact of OS in plasma and cerebrospinal fluid (CSF) on clinical outcomes in patients with ICH. A total of 19 ICH (volume > 30 cc) patients and 29 control patients were included. From day one until seven, blood and CSF samples were obtained, and ICH volume was calculated. OS markers, like malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione-sulfhydryl (GSH), and the total antioxidant status (TAS) were measured. Clinical data on treatment and outcome were determined. Patients with mRS ≤ 4 showed significantly elevated SOD and GSH-Px levels in plasma compared to patients with poor CO (p = 0.004; p = 0.002). Initial increased TAS in plasma and increased MDA in CSF were linked to an unfavorable outcome after six months (p = 0.06, r = 0.45; p = 0.05, r = 0.44). A higher ICH volume was associated with a worse outcome at week six (p = 0.04, r = 0.47). OS plays a significant role in SBI. Larger ICHs, elevated MDA in CSF, and TAS in plasma were associated with a detrimental outcome, whereas higher plasma-SOD and -GSH-Px were associated with a favorable outcome.

scholarly journals Role of the Ubiquitin System in Chronic Pain

2021 ◽  
Vol 14 ◽  
Author(s):  
Jiurong Cheng ◽  
Yingdong Deng ◽  
Jun Zhou
Keyword(s):  
Chronic Pain ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Public Health Issue ◽  
Deubiquitinating Enzyme ◽  
Ubiquitin System ◽  
Significant Public Health ◽  
Underlying Mechanisms ◽  
Insight Into

As a significant public health issue, chronic pain, mainly neuropathic pain (NP) and inflammatory pain, has a severe impact. The underlying mechanisms of chronic pain are enigmatic at present. The roles of ubiquitin have been demonstrated in various physiological and pathological conditions and underscore its potential as therapeutic targets. The dysfunction of the component of the ubiquitin system that occurs during chronic pain is rapidly being discovered. These results provide insight into potential molecular mechanisms of chronic pain. Chronic pain is regulated by ubiquitination, SUMOylation, ubiquitin ligase, and deubiquitinating enzyme (DUB), etc. Insight into the mechanism of the ubiquitin system regulating chronic pain might contribute to relevant therapeutic targets and the development of novel analgesics.

scholarly journals Therapeutic Challenges and Emerging Treatment Targets for Pulmonary Hypertension in Left Heart Disease

2021 ◽  
Author(s):  
Christelle Lteif ◽  
Ali Ataya ◽  
Julio D. Duarte
Keyword(s):  
Pulmonary Hypertension ◽  
Heart Disease ◽  
Therapeutic Targets ◽  
Pulmonary Artery Hypertension ◽  
Left Heart ◽  
Genetic Associations ◽  
Mortality And Morbidity ◽  
Left Heart Disease ◽  
Underlying Mechanisms ◽  
Phosphodiesterase 5

Abstract Pulmonary hypertension (PH) attributable to left heart disease (LHD) is believed to be the most common form of PH and is strongly associated with increased mortality and morbidity in this patient population. Specific therapies for PH‐LHD have not yet been identified and the use of pulmonary artery hypertension‐targeted therapies in PH‐LHD are not recommended. Endothelin receptor antagonists, phosphodiesterase‐5 inhibitors, guanylate cyclase stimulators, and prostacyclins have all been studied in PH‐LHD with conflicting results. Understanding the mechanisms underlying PH‐LHD could potentially provide novel therapeutic targets. Fibrosis, oxidative stress, and metabolic syndrome have been proposed as pathophysiological components of PH‐LHD. Genetic associations have also been identified, offering additional mechanisms with biological plausibility. This review summarizes the evidence and challenges for treatment of PH‐LHD and focuses on underlying mechanisms on the horizon that could develop into potential therapeutic targets for this disease.

scholarly journals The role of oxidative stress in perinatal hypoxic-ischemic brain injury

2012 ◽  
Vol 140 (1-2) ◽  
pp. 35-41 ◽  
Author(s):  
Brankica Vasiljevic ◽  
Svjetlana Maglajlic-Djukic ◽  
Miroslava Gojnic ◽  
Sanja Stankovic
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Brain Damage ◽  
Ischemic Brain Injury ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Hypoxic Ischemic Brain Injury ◽  
Gpx Activity ◽  
Neurodevelopment Outcome

Introduction. The pathogenesis of perinatal hypoxic-ischemic brain damage is highly complex. Objective. The aim of this study was to assess the role of oxidative stress in hypoxic-ischemic brain injury and subsequent abnormal neurological outcome in infants with perinatal hypoxic-ischemic encephalopathy (HIE). We estimated perinatal oxidative brain damage measuring activity of glutathione peroxidase (GPX) in cerebrospinal fluid (CSF) as an indirect biomarker of free radical production during cerebral hypoxia-ischemia in correlation with the level of intracellular enzyme neuron specific enolase (NSE) in CSF as a biomarker of extend of brain injury. Methods. Ninety neonates (>32 GA) with perinatal HIE were enrolled prospectively. HIE was categorized into three stages according Sarnat and Sarnat clinical scoring system and changes seen on amplitude integrated EEG. CSF for GPX analysis and NSE analysis was taken in the first 72 hours of life. Neurodevelopment outcome was assessed at 12 months of corrected gestational age. Results. GPX activity in CSF was in good relation with clinical stage of HIE (p<0.0001) and GA (p<0.0001) and significantly corresponded with subsequent neurodevelopment outcome (p<0.001). GPX activity in CSF showed a strong correlation with NSE levels in CSF (p<0.001) as the biomarker of extent of brain injury. Conclusion. Our results suggest that oxidative stress might be important contributing factor in perinatal hypoxic-ischemic brain damage, particularly in preterm neonates.

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 Young plasma ameliorates aging-related acute brain injury after intracerebral hemorrhage

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Jun-Jie Yuan ◽  
Qin Zhang ◽  
Chang-Xiong Gong ◽  
Fa-Xiang Wang ◽  
Jia-Cheng Huang ◽  
...  
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Brain Damage ◽  
Mrna Level ◽  
Acute Brain Injury ◽  
Aging Brain ◽  
Neural Cells ◽  
Neuroprotective Effects ◽  
The Brain ◽  
Brain Tissues

Abstract Aging has been shown to contribute to both the declined biofunctions of aging brain and aggravation of acute brain damage, and the former could be reversed by young plasma. These results suggest that young plasma treatment may also reduce the acute brain damage induced by intracerebral hemorrhage (ICH). In the present study, we first found that the administration of young plasma significantly reduced the mortality and neurological deficit score in aging ICH rodents, which might be due to the decreased brain water content, damaged neural cells, and increased survival neurons around the perihematomal brain tissues. Then, proteomics analysis was used to screen out the potential neuroprotective circulating factors and the results showed that many factors were changed in health human plasma among young, adult, and old population. Among these significantly changed factors, the plasma insulin-like growth factor 1 (IGF-1) level was significantly decreased with age, which was further confirmed both in human and rats detected by ELISA. Additionally, the brain IGF-1 protein level in aging ICH rats was markedly decreased when compared with young rats. Interestingly, the relative decreased brain IGF-1 level was reversed by the treatment of young plasma in aging ICH rats, while the mRNA level was non-significantly changed. Furthermore, the IGF-1 administration significantly ameliorated the acute brain injury in aging ICH rats. These results indicated that young circulating factors, like IGF-1, may enter brain tissues to exert neuroprotective effects, and young plasma may be considered as a novel therapeutic approach for the clinical treatment of aging-related acute brain injury.

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