Toll-Like Receptor 4 Knockdown Attenuates Brain Damage and Neuroinflammation After Traumatic Brain Injury via Inhibiting Neuronal Autophagy and Astrocyte Activation

2017 ◽  
Vol 38 (5) ◽  
pp. 1009-1019 ◽  
Author(s):  
Hongsheng Jiang ◽  
Yanzhou Wang ◽  
Xin Liang ◽  
Xiaofeng Xing ◽  
Xiuzhen Xu ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Damage ◽  
Toll Like Receptor ◽  
Astrocyte Activation ◽  
Toll Like Receptor 4 ◽  
Neuronal Autophagy

Toll like receptor 4 activation can be either detrimental or beneficial following mild repetitive traumatic brain injury depending on timing of activation

2017 ◽  
Vol 64 ◽  
pp. 124-139 ◽  
Author(s):  
Frances Corrigan ◽  
Alina Arulsamy ◽  
Lyndsey E. Collins-Praino ◽  
Joshua L. Holmes ◽  
Robert Vink
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4

Forsythiaside-A Alleviates Traumatic Brain Injury by Regulating Toll-Like Receptor 4/Myeloid Differentiation Factor 88/Nuclear Factor-Kappa B Signaling Pathway

2021 ◽  
Vol 19 (3) ◽  
pp. 326-332
Author(s):  
Jinsi Tian ◽  
Xiaoya Xu ◽  
Da Tian
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Signaling Pathway ◽  
Brain Tissue ◽  
Nuclear Factor Kappa B ◽  
Myeloid Differentiation ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Myeloid Differentiation Factor

Traumatic brain injury refers to brain injury caused by mechanical impact often leading to severe morbidity and mortality. Despite increasing awareness, there are no effective treatments strategies. Therefore, there is a need to develop new effective treatments for this injury. Forsythiaside A is a monomer of phenylethanolglucoside extracted from Forsythia, which has a wide range of pharmacological properties including protective effects on brain tissue. Herein, using a rat model of traumatic brain injury, we have shown that forsythiaside A can improve nerve function and brain tissue injury in rats with traumatic brain injury, and reduce brain inflammation and neuronal apoptosis. We have further shown that forsythiaside A regulates toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-kappa B signaling pathway. This opens the possibility of a potentially promising therapeutic drug for the treatment of traumatic brain injury.

scholarly journals High mobility group box protein-1 promotes cerebral edema after traumatic brain injury via activation of toll-like receptor 4

Glia ◽  
2013 ◽  
Vol 62 (1) ◽  
pp. 26-38 ◽  
Author(s):  
Melissa D. Laird ◽  
Jessica S. Shields ◽  
Sangeetha Sukumari-Ramesh ◽  
Donald E. Kimbler ◽  
R. David Fessler ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cerebral Edema ◽  
High Mobility ◽  
High Mobility Group ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4

scholarly journals S100A8 Promotes Inflammation via Toll-Like Receptor 4 After Experimental Traumatic Brain Injury

2021 ◽  
Vol 14 ◽  
Author(s):  
Guo-Yuan He ◽  
Chen-Hui Zhao ◽  
De-Gang Wu ◽  
Hao Cheng ◽  
Le-An Sun ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Western Blot ◽  
Inflammatory Cytokines ◽  
Enzyme Linked Immunosorbent Assay ◽  
Intracerebroventricular Administration ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
The Brain

IntroductionS100 calcium-binding protein A8 (S100A8) is also known as macrophage-related protein 8, which is involved in various pathological processes in the central nervous system post-traumatic brain injury (TBI), and plays a critical role in inducing inflammatory cytokines. Accumulating evidences have indicated that toll-like receptor 4 (TLR4) is considered to be involved in inflammatory responses post TBI. The present study was designed to analyze the hypothesis that S100A8 is the key molecule that induces inflammation via TLR4 in TBI.MethodsThe weight-drop TBI model was used and randomly implemented on mice that were categorized into six groups: Sham, NS, S100A8, S100A8+TAK-242, TBI, and TBI+TAK-242 groups. In the S100A8+TAK-242 and TBI+TAK-242 groups, at half an hour prior to the intracerebroventricular administration of S100A8 or TBI, mice were intraperitoneally treated with TAK-242 that acts as a selective antagonist and inhibitor of TLR4. Furthermore, the protein recombinant of S100A8 was injected into the lateral ventricle of the brain of mice in the S100A8 and S100A8+TAK-242 groups. Sterile normal saline was injected into the lateral ventricle in the NS group. To evaluate the association between S100A8 and TLR4, Western blot, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and Nissl staining were employed. Simultaneously, the neurological score and brain water content were assessed. In the in vitro analysis, BV-2 microglial cells were stimulated with lipopolysaccharide LPS or S100A8 recombinant protein, with or without TAK-242. The expression of the related proteins was subsequently detected by Western blot or enzyme-linked immunosorbent assay.ResultsThe levels of S100A8 protein and pro-inflammatory cytokines were significantly elevated after TBI. There was a reduction in the neurological scores of non-TBI animals with remarkable severe brain edema after the intracerebroventricular administration of S100A8. Furthermore, the TLR4, p-p65, and myeloid differentiation factor 88 (MyD88) levels were elevated after the administration of S100A8 or TBI, which could be restored by TAK-242. Meanwhile, in the in vitro analysis, due to the stimulation of S100A8 or LPS, there was an upregulation of p-p65 and MyD88, which could also be suppressed by TAK-242.ConclusionThe present study demonstrated that the TLR4-MyD88 pathway was activated by S100A8, which is essential for the development of inflammation in the brain after TBI.

scholarly journals Inhaled Nitric Oxide Reduces Secondary Brain Damage after Traumatic Brain Injury in Mice

2012 ◽  
Vol 33 (2) ◽  
pp. 311-318 ◽  
Author(s):  
Nicole A Terpolilli ◽  
Seong-Woong Kim ◽  
Serge C Thal ◽  
Wolfgang M Kuebler ◽  
Nikolaus Plesnila
Keyword(s):  
Nitric Oxide ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Damage ◽  
Brain Regions ◽  
Lesion Volume ◽  
Effective Treatment Option ◽  
Secondary Brain Damage ◽  
Edema Formation ◽  
Regional Ischemia

Ischemia, especially pericontusional ischemia, is one of the leading causes of secondary brain damage after traumatic brain injury (TBI). So far efforts to improve cerebral blood flow (CBF) after TBI were not successful because of various reasons. We previously showed that nitric oxide (NO) applied by inhalation after experimental ischemic stroke is transported to the brain and induces vasodilatation in hypoxic brain regions, thus improving regional ischemia, thereby improving brain damage and neurological outcome. As regional ischemia in the traumatic penumbra is a key mechanism determining secondary posttraumatic brain damage, the aim of the current study was to evaluate the effect of NO inhalation after experimental TBI. NO inhalation significantly improved CBF and reduced intracranial pressure after TBI in male C57 Bl/6 mice. Long-term application (24 hours NO inhalation) resulted in reduced lesion volume, reduced brain edema formation and less blood–brain barrier disruption, as well as improved neurological function. No adverse effects, e.g., on cerebral auto-regulation, systemic blood pressure, or oxidative damage were observed. NO inhalation might therefore be a safe and effective treatment option for TBI patients.

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.

Suppression of FoxO3a attenuates neurobehavioral deficits after traumatic brain injury through inhibiting neuronal autophagy

2018 ◽  
Vol 337 ◽  
pp. 271-279 ◽  
Author(s):  
Liqian Sun ◽  
Manman Zhao ◽  
Man Liu ◽  
Peng Su ◽  
Jingbo Zhang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neurobehavioral Deficits ◽  
Neuronal Autophagy

Toll-like receptor 2 contributes to glial cell activation and heme oxygenase-1 expression in traumatic brain injury

2008 ◽  
Vol 431 (2) ◽  
pp. 123-128 ◽  
Author(s):  
Chanhee Park ◽  
Ik-Hyun Cho ◽  
Donghoon Kim ◽  
Eun-Kyeong Jo ◽  
Se-Young Choi ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Glial Cell ◽  
Heme Oxygenase ◽  
Cell Activation ◽  
Heme Oxygenase 1 ◽  
Toll Like Receptor ◽  
Glial Cell Activation ◽  
Toll Like Receptor 2

scholarly journals Unraveling the Biopsychosocial Factors of Fatigue and Sleep Problems After Traumatic Brain Injury: Protocol for a Multicenter Longitudinal Cohort Study (Preprint)

2018 ◽  
Author(s):  
Jessica Bruijel ◽  
Sven Z Stapert ◽  
Annemiek Vermeeren ◽  
Jennie L Ponsford ◽  
Caroline M van Heugten
Keyword(s):  
Social Support ◽  
Traumatic Brain Injury ◽  
Cohort Study ◽  
Brain Injury ◽  
Brain Damage ◽  
Emotional State ◽  
Sleep Problems ◽  
Family Participation ◽  
Severe Tbi ◽  
Support Family

BACKGROUND Fatigue and sleep problems are common after a traumatic brain injury (TBI) and are experienced as highly distressing symptoms, playing a significant role in the recovery trajectory, and they can drastically impact the quality of life and societal participation of the patient and their family and friends. However, the etiology and development of these symptoms are still uncertain. OBJECTIVE The aim of this study is to examine the development of fatigue and sleep problems following moderate to severe TBI and to explore the changes in underlying biological (pain, brain damage), psychological (emotional state), and social (support family, participation) factors across time. METHODS This study is a longitudinal multicenter observational cohort study with 4 measurement points (3, 6, 12, and 18 months postinjury) including subjective questionnaires and cognitive tasks, preceded by 7 nights of actigraphy combined with a sleep diary. Recruitment of 137 moderate to severe TBI patients presenting at emergency and neurology departments or rehabilitation centers across the Netherlands is anticipated. The evolution of fatigue and sleep problems following TBI and their association with possible underlying biological (pain, brain damage), psychological (emotional state), and social (support family, participation) factors will be examined. RESULTS Recruitment of participants for this longitudinal cohort study started in October 2017, and the enrollment of participants is ongoing. The first results are expected at the end of 2020. CONCLUSIONS To the authors’ knowledge, this is the first study that examines the development of both post-TBI fatigue and sleep longitudinally within a biopsychosocial model in moderate to severe TBI using both subjective and objective measures. Identification of modifiable factors such as mood and psychosocial stressors may give direction to the development of interventions for fatigue and sleep problems post-TBI. CLINICALTRIAL Netherlands Trial Register NTR7162; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=7162 (Archived by WebCite at http://www.webcitation.org/6z3mvNLuy) INTERNATIONAL REGISTERED REPOR RR1-10.2196/11295

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