scholarly journals HMGB1 a-Box Reverses Brain Edema and Deterioration of Neurological Function in a Traumatic Brain Injury Mouse Model

2018 ◽  
Vol 46 (6) ◽  
pp. 2532-2542 ◽  
Author(s):  
Lijun Yang ◽  
Feng Wang ◽  
Liang Yang ◽  
Yunchao Yuan ◽  
Yan Chen ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Edema ◽  
Therapeutic Potential ◽  
High Mobility ◽  
Neurological Injury ◽  
Secondary Brain Injury ◽  
Cell Degeneration ◽  
Injured Brain ◽  
Walking Tests

Background/Aims: Traumatic brain injury (TBI) is a complex neurological injury in young adults lacking effective treatment. Emerging evidences suggest that inflammation contributes to the secondary brain injury following TBI, including breakdown of the blood brain barrier (BBB), subsequent edema and neurological deterioration. High mobility group box-1 (HMGB1) has been identified as a key cytokine in the inflammation reaction following TBI. Here, we investigated the therapeutic efficacy of HMGB1 A-box fragment, an antagonist competing with full-length HMGB1 for receptor binding, against TBI. Methods: TBI was induced by controlled cortical impact (CCI) in adult male mice. HMGB1 A-box fragment was given intravenously at 2 mg/kg/day for 3 days after CCI. HMGB1 A-box-treated CCI mice were compared with saline-treated CCI mice and sham mice in terms of BBB disruption evaluated by Evan’s blue extravasation, brain edema by brain water content, cell death by propidium iodide staining, inflammation by Western blot and ELISA assay for cytokine productions, as well as neurological functions by the modified Neurological Severity Score, wire grip and beam walking tests. Results: HMGB1 A-box reversed brain damages in the mice following TBI. It significantly reduced brain edema by protecting integrity of the BBB, ameliorated cell degeneration, and decreased expression of pro-inflammatory cytokines released in injured brain after TBI. These cellular and molecular effects were accompanied by improved behavioral performance in TBI mice. Notably, HMGB1 A-box blocked IL-1β-induced HMGB1 release, and preferentially attenuated TLR4, Myd88 and P65 in astrocyte cultures. Conclusion: Our data suggest that HMGB1 is involved in CCI-induced TBI, which can be inhibited by HMGB1 A-box fragment. Therefore, HMGB1 A-box fragment may have therapeutic potential for the secondary brain damages in TBI.

scholarly journals Beneficial Effects of Ethyl Pyruvate through Inhibiting High-Mobility Group Box 1 Expression and TLR4/NF-κB Pathway after Traumatic Brain Injury in the Rat

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Xingfen Su ◽  
Handong Wang ◽  
Jinbing Zhao ◽  
Hao Pan ◽  
Lei Mao
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Ethyl Pyruvate ◽  
Apoptotic Cell ◽  
High Mobility ◽  
High Mobility Group ◽  
Male Rats ◽  
Vehicle Group ◽  
Secondary Brain Injury ◽  
Protective Effects

Ethyl pyruvate (EP) has demonstrated neuroprotective effects against acute brain injury through its anti-inflammatory action. The nuclear protein high-mobility group box 1 (HMGB1) can activate inflammatory pathways when released from dying cells. This study was designed to investigate the protective effects of EP against secondary brain injury in rats after Traumatic Brain Injury (TBI). Adult male rats were randomly divided into three groups: (1) Sham + vehicle group, (2) TBI + vehicle group, and (3) TBI + EP group (n=30per group). Right parietal cortical contusion was made by using a weight-dropping TBI method. In TBI + EP group, EP was administered intraperitoneally at a dosage of 75 mg/kg at 5 min, 1 and 6 h after TBI. Brain samples were harvested at 24 h after TBI. We found that EP treatment markedly inhibited the expressions of HMGB1 and TLR4, NF-κB DNA binding activity and inflammatory mediators, such as IL-1β, TNF-αand IL-6. Also, EP treatment significantly ameliorated beam walking performance, brain edema, and cortical apoptotic cell death. These results suggest that the protective effects of EP may be mediated by the reduction of HMGB1/TLR4/NF-κB-mediated inflammatory response in the injured rat brain.

scholarly journals Co-Expression Network Analysis of MicroRNAs and Proteins in Severe Traumatic Brain Injury: A Systematic Review

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2425
Author(s):  
Claire Osgood ◽  
Zubair Ahmed ◽  
Valentina Di Pietro
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Therapeutic Potential ◽  
Psychosocial Problems ◽  
Bioinformatic Analysis ◽  
Healthcare Services ◽  
Secondary Brain Injury ◽  
Mortality And Morbidity ◽  
Severe Tbi ◽  
Novel Target

Traumatic brain injury (TBI) represents one of the leading causes of mortality and morbidity worldwide, placing an enormous socioeconomic burden on healthcare services and communities around the world. Survivors of TBI can experience complications ranging from temporary neurological and psychosocial problems to long-term, severe disability and neurodegenerative disease. The current lack of therapeutic agents able to mitigate the effects of secondary brain injury highlights the urgent need for novel target discovery. This study comprises two independent systematic reviews, investigating both microRNA (miRNA) and proteomic expression in rat models of severe TBI (sTBI). The results were combined to perform integrated miRNA-protein co-expression analyses with the aim of uncovering the potential roles of miRNAs in sTBI and to ultimately identify new targets for therapy. Thirty-four studies were included in total. Bioinformatic analysis was performed to identify any miRNA–protein associations. Endocytosis and TNF signalling pathways were highlighted as common pathways involving both miRNAs and proteins found to be differentially expressed in rat brain tissue following sTBI, suggesting efforts to find novel therapeutic targets that should be focused here. Further high-quality investigations are required to ascertain the involvement of these pathways and their miRNAs in the pathogenesis of TBI and other CNS diseases and to therefore uncover those targets with the greatest therapeutic potential.

scholarly journals Inhibitory Effect on Cerebral Inflammatory Response following Traumatic Brain Injury in Rats: A Potential Neuroprotective Mechanism of N-Acetylcysteine

2008 ◽  
Vol 2008 ◽  
pp. 1-8 ◽  
Author(s):  
Gang Chen ◽  
Jixin Shi ◽  
Zhigang Hu ◽  
Chunhua Hang
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Inflammatory Response ◽  
Interleukin 1 ◽  
Inhibitory Effect ◽  
Intercellular Adhesion Molecule ◽  
Secondary Brain Injury ◽  
Intercellular Adhesion Molecule 1 ◽  
Injured Brain ◽  
Inflammatory Proteins

Although N-acetylcysteine (NAC) has been shown to be neuroprotective for traumatic brain injury (TBI), the mechanisms for this beneficial effect are still poorly understood. Cerebral inflammation plays an important role in the pathogenesis of secondary brain injury after TBI. However, it has not been investigated whether NAC modulates TBI-induced cerebral inflammatory response. In this work, we investigated the effect of NAC administration on cortical expressions of nuclear factor kappa B (NF-κB) and inflammatory proteins such as interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), and intercellular adhesion molecule-1 (ICAM-1) after TBI. As a result, we found that NF-κB, proinflammatory cytokines, and ICAM-1 were increased in all injured animals. In animals given NAC post-TBI, NF-κB, IL-1β, TNF-α, and ICAM-1 were decreased in comparison to vehicle-treated animals. Measures of IL-6 showed no change after NAC treatment. NAC administration reduced brain edema, BBB permeability, and apoptotic index in the injured brain. The results suggest that post-TBI NAC administration may attenuate inflammatory response in the injured rat brain, and this may be one mechanism by which NAC ameliorates secondary brain damage following TBI.

scholarly journals Biologic Effect of Hydrogen Sulfide and Its Role in Traumatic Brain Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Jiaxin Zhang ◽  
Shaoyi Zhang ◽  
Haiyan Shan ◽  
Mingyang Zhang
Keyword(s):  
Traumatic Brain Injury ◽  
Hydrogen Sulfide ◽  
Brain Injury ◽  
Therapeutic Potential ◽  
Long Term Potentiation ◽  
Secondary Brain Injury ◽  
Term Potentiation ◽  
Great Hope ◽  
Biologic Effects ◽  
Physiological Dose

Ever since endogenous hydrogen sulfide (H2S) was found in mammals in 1989, accumulated evidence has demonstrated that H2S functions as a novel neurological gasotransmitter in brain tissues and may play a key role in traumatic brain injury. It has been proved that H2S has an antioxidant, anti-inflammatory, and antiapoptosis function in the neuron system and functions as a neuroprotective factor against secondary brain injury. In addition, H2S has other biologic effects such as regulating the intracellular concentration of Ca2+, facilitating hippocampal long-term potentiation (LTP), and activating ATP-sensitive K channels. Due to the toxic nature of H2S when exceeding the physiological dose in the human body, only a small amount of H2S-related therapies was applied to clinical treatment. Therefore, it has huge therapeutic potential and has great hope for recovering patients with traumatic brain injury.

The role of NLRP3 in traumatic brain injury and its regulation by pioglitazone

2020 ◽  
Vol 133 (4) ◽  
pp. 1083-1091
Author(s):  
Ho Jun Yi ◽  
Jung Eun Lee ◽  
Dong Hoon Lee ◽  
Young Il Kim ◽  
Chul Bum Cho ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Western Blot ◽  
Brain Edema ◽  
Cerebral Edema ◽  
Sham Group ◽  
Secondary Brain Injury ◽  
Treatment Groups ◽  
Perilesional Edema

OBJECTIVEPerilesional edema is a predominant mechanism underlying secondary brain injury after traumatic brain injury (TBI). Perilesional edema is characterized by inflammation, production of proinflammatory cytokines, and migration of peripheral immune cells into the brain. The nucleotide-binding domain and leucine-rich repeat (NLR) family pyrin domain–containing 3 protein (NLRP3) is a key component of secondary injury. Pioglitazone regulates NLRP3 and other inflammatory cytokines. In the present study, the role of NLRP3 and the pharmacological effects of pioglitazone were investigated in animal TBI models.METHODSBrain contusion was induced in a weight drop model involving 3 groups of mice: C57 BL/6 (sham group), NLRP3 knockout (K/O group), and pioglitazone-treated mice (treatment group). The percentage of brain water content of the 3 groups of mice was compared over a period of time. Western blot, immunohistochemistry, and immunofluorescence analyses were conducted to investigate NLRP3-related inflammasomes and the effects of pioglitazone in the TBI models.RESULTSBrain edema was the highest on day 3 after TBI in the sham group. Brain edema in both the K/O and the treatment groups was lower than in the sham group. In Western blot, the expression of inflammasomes was higher after TBI in the sham group, but the expression of interleukin-1β, caspase-1, and NLRP3 was decreased significantly following treatment with pioglitazone. The expression of GFAP (glial fibrillary acidic protein) and Iba1 was decreased in both the K/O and treatment groups. In addition, confocal microscopy revealed a decrease in microglial cell and astrocyte activation following pioglitazone therapy.CONCLUSIONSThe inflammasome NLRP3 plays a pivotal role in regulating cerebral edema and secondary inflammation. Interestingly, pioglitazone reduced cerebral edema and immune response after TBI by downregulating the effects of NLRP3. These results suggest that the clinical application of pioglitazone may be a neuroprotective strategy in TBI.

Traumatic Brain Injury: A Trauma Surgeon's Perspective

2012 ◽  
Vol 22 (3) ◽  
pp. 82-89
Author(s):  
Oscar D. Guillamondegui
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Multidisciplinary Approach ◽  
Trauma Team ◽  
The United States ◽  
Long Term Outcomes ◽  
Term Care ◽  
Injured Brain ◽  
The Moment

Traumatic brain injury (TBI) is a serious epidemic in the United States. It affects patients of all ages, race, and socioeconomic status (SES). The current care of these patients typically manifests after sequelae have been identified after discharge from the hospital, long after the inciting event. The purpose of this article is to introduce the concept of identification and management of the TBI patient from the moment of injury through long-term care as a multidisciplinary approach. By promoting an awareness of the issues that develop around the acutely injured brain and linking them to long-term outcomes, the trauma team can initiate care early to alter the effect on the patient, family, and community. Hopefully, by describing the care afforded at a trauma center and by a multidisciplinary team, we can bring a better understanding to the armamentarium of methods utilized to treat the difficult population of TBI patients.

scholarly journals Ulinastatin alleviates traumatic brain injury by reducing endothelin-1

2020 ◽  
Vol 12 (1) ◽  
pp. 001-008
Author(s):  
Ting Liu ◽  
Xing-Zhi Liao ◽  
Mai-Tao Zhou
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Western Blot ◽  
Water Content ◽  
Brain Edema ◽  
Rat Model ◽  
Neurosurgical Procedures ◽  
Brain Water Content ◽  
The Brain ◽  
Brain Water

Abstract Background Brain edema is one of the major causes of fatality and disability associated with injury and neurosurgical procedures. The goal of this study was to evaluate the effect of ulinastatin (UTI), a protease inhibitor, on astrocytes in a rat model of traumatic brain injury (TBI). Methodology A rat model of TBI was established. Animals were randomly divided into 2 groups – one group was treated with normal saline and the second group was treated with UTI (50,000 U/kg). The brain water content and permeability of the blood–brain barrier were assessed in the two groups along with a sham group (no TBI). Expression of the glial fibrillary acidic protein, endthelin-1 (ET-1), vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP-9) were measured by immunohistochemistry and western blot. Effect of UTI on ERK and PI3K/AKT signaling pathways was measured by western blot. Results UTI significantly decreased the brain water content and extravasation of the Evans blue dye. This attenuation was associated with decreased activation of the astrocytes and ET-1. UTI treatment decreased ERK and Akt activation and inhibited the expression of pro-inflammatory VEGF and MMP-9. Conclusion UTI can alleviate brain edema resulting from TBI by inhibiting astrocyte activation and ET-1 production.

A pre-injury high ethanol intake in rats promotes brain edema following traumatic brain injury

2014 ◽  
Vol 28 (6) ◽  
pp. 739-745 ◽  
Author(s):  
Weichuan Wu ◽  
Runfa Tian ◽  
Shuyu Hao ◽  
Feifan Xu ◽  
Xiang Mao ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Edema ◽  
Ethanol Intake ◽  
High Ethanol

scholarly journals Transcranial Direct Current Stimulation as a Treatment Tool for Mild Traumatic Brain Injury

2021 ◽  
Vol 11 (6) ◽  
pp. 806
Author(s):  
Thorsten Rudroff ◽  
Craig D. Workman
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Direct Current ◽  
Transcranial Direct Current Stimulation ◽  
Therapeutic Potential ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Motor Impairment ◽  
Direct Current Stimulation ◽  
Main Technique

Mild traumatic brain injury (mTBI) has been defined as a transient (<24 h) condition of confusion and/or loss of consciousness for less than 30 min after brain injury and can result in short- and long-term motor and cognitive impairments. Recent studies have documented the therapeutic potential of non-invasive neuromodulation techniques for the enhancement of cognitive and motor function in mTBI. Alongside repetitive transcranial magnetic stimulation (rTMS), the main technique used for this purpose is transcranial direct current stimulation (tDCS). The focus of this review was to provide a detailed, comprehensive (i.e., both cognitive and motor impairment) overview of the literature regarding therapeutic tDCS paradigms after mTBI. A publication search of the PubMed, Scopus, CINAHL, and PsycINFO databases was performed to identify records that applied tDCS in mTBI. The publication search yielded 14,422 records from all of the databases, however, only three met the inclusion criteria and were included in the final review. Based on the review, there is limited evidence of tDCS improving cognitive and motor performance. Surprisingly, there were only three studies that used tDCS in mTBI, which highlights an urgent need for more research to provide additional insights into ideal therapeutic brain targets and optimized stimulation parameters.

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