The danger zone: Systematic review of the role of HMGB1 danger signalling in traumatic brain injury

Parker, Taylor M.; Nguyen, Austin Huy; Rabang, Joshua; Patil, Arun Angelo; Agrawal, Devendra K.

doi:10.1080/02699052.2016.1217045

Cited by 43 publications

(48 citation statements)

References 20 publications

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“…Similarly, TNF‐α was involved in both secondary brain damage and regenerative recovery after experimental stroke . The pathologic involvement of inflammation is supported by evidence that excessive brain levels of IL‐1β, IL‐6, TNF‐α (exceeding several times their serum changes), or HMGB1 contribute to experimental acute and chronic seizures and SE‐induced epileptogenesis . Importantly, HMGB1 antibodies have been shown to prevent epileptogenesis in the mouse intrahippocampal kainate model .…”

Section: Inflammatory Processes After Acquired Brain Injuriesmentioning

confidence: 96%

Commonalities in epileptogenic processes from different acute brain insults: Do they translate?

et al. 2017

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Summary The most common forms of acquired epilepsies arise following acute brain insults such as traumatic brain injury, stroke, or central nervous system infections. Treatment is effective for only 60%‐70% of patients and remains symptomatic despite decades of effort to develop epilepsy prevention therapies. Recent preclinical efforts are focused on likely primary drivers of epileptogenesis, namely inflammation, neuron loss, plasticity, and circuit reorganization. This review suggests a path to identify neuronal and molecular targets for clinical testing of specific hypotheses about epileptogenesis and its prevention or modification. Acquired human epilepsies with different etiologies share some features with animal models. We identify these commonalities and discuss their relevance to the development of successful epilepsy prevention or disease modification strategies. Risk factors for developing epilepsy that appear common to multiple acute injury etiologies include intracranial bleeding, disruption of the blood‐brain barrier, more severe injury, and early seizures within 1 week of injury. In diverse human epilepsies and animal models, seizures appear to propagate within a limbic or thalamocortical/corticocortical network. Common histopathologic features of epilepsy of diverse and mostly focal origin are microglial activation and astrogliosis, heterotopic neurons in the white matter, loss of neurons, and the presence of inflammatory cellular infiltrates. Astrocytes exhibit smaller K+ conductances and lose gap junction coupling in many animal models as well as in sclerotic hippocampi from temporal lobe epilepsy patients. There is increasing evidence that epilepsy can be prevented or aborted in preclinical animal models of acquired epilepsy by interfering with processes that appear common to multiple acute injury etiologies, for example, in post–status epilepticus models of focal epilepsy by transient treatment with a trkB/PLCγ1 inhibitor, isoflurane, or HMGB1 antibodies and by topical administration of adenosine, in the cortical fluid percussion injury model by focal cooling, and in the albumin posttraumatic epilepsy model by losartan. Preclinical studies further highlight the roles of mTOR1 pathways, JAK‐STAT3, IL‐1R/TLR4 signaling, and other inflammatory pathways in the genesis or modulation of epilepsy after brain injury. The wealth of commonalities, diversity of molecular targets identified preclinically, and likely multidimensional nature of epileptogenesis argue for a combinatorial strategy in prevention therapy. Going forward, the identification of impending epilepsy biomarkers to allow better patient selection, together with better alignment with multisite preclinical trials in animal models, should guide the clinical testing of new hypotheses for epileptogenesis and its prevention.

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Section: Inflammatory Processes After Acquired Brain Injuriesmentioning

confidence: 96%

Commonalities in epileptogenic processes from different acute brain insults: Do they translate?

et al. 2017

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“…Survivors live the rest of their lives with cognitive, motor, behavioral or speech and language disabilities ( Richard et al, 2017 ). However, the pathophysiology of TBI is still elusive and a tremendous research must be made to explore the progression of neurodegeneration and the ensuing inflammatory processes ( Parker et al, 2017 ). It is currently unavailable to attenuate the pathological process of TBI and improve neurological deficits ( Jiang et al, 2018 ).…”

Section: Role Of Hmgb1 In Tbimentioning

confidence: 99%

“…Excessive inflammation resulting from activation of the HMGB1/TLR4 pathway in the brain has been implicated in TBI and ischemia-reperfusion injury ( Yang et al, 2011 ). However, the mechanistic interlinkage between intracellular danger signaling, which involves the nuclear chromatin-binding factor, HMGB1 and inflammatory pathways after TBI is not yet fully understood ( Parker et al, 2017 ). There is an increased understanding that TBI may induce activation of HMGB1/TLR4/RAGE/NF-κB signaling pathway and inflammatory cytokine expression, which would induce and/or aggravate the secondary brain injury where HMGB1 is supposed to implicate a critical role in promoting inflammation and aggravating damage after TBI ( Xiangjin et al, 2014 ) ( Figure 2 ).…”

Section: Role Of Hmgb1 In Tbimentioning

confidence: 99%

HMGB1: A Common Biomarker and Potential Target for TBI, Neuroinflammation, Epilepsy, and Cognitive Dysfunction

et al. 2018

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High mobility group box protein 1 (HMGB1) is a ubiquitous nuclear protein released by glia and neurons upon inflammasome activation and activates receptor for advanced glycation end products (RAGE) and toll-like receptor (TLR) 4 on the target cells. HMGB1/TLR4 axis is a key initiator of neuroinflammation. In recent days, more attention has been paid to HMGB1 due to its contribution in traumatic brain injury (TBI), neuroinflammatory conditions, epileptogenesis, and cognitive impairments and has emerged as a novel target for those conditions. Nevertheless, HMGB1 has not been portrayed as a common prognostic biomarker for these HMGB1 mediated pathologies. The current review discusses the contribution of HMGB1/TLR4/RAGE signaling in several brain injury, neuroinflammation mediated disorders, epileptogenesis and cognitive dysfunctions and in the light of available evidence, argued the possibilities of HMGB1 as a common viable biomarker of the above mentioned neurological dysfunctions. Furthermore, the review also addresses the result of preclinical studies focused on HMGB1 targeted therapy by the HMGB1 antagonist in several ranges of HMGB1 mediated conditions and noted an encouraging result. These findings suggest HMGB1 as a potential candidate to be a common biomarker of TBI, neuroinflammation, epileptogenesis, and cognitive dysfunctions which can be used for early prediction and progression of those neurological diseases. Future study should explore toward the translational implication of HMGB1 which can open the windows of opportunities for the development of innovative therapeutics that could prevent several associated HMGB1 mediated pathologies discussed herein.

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“…HMGB1 is a dual function protein that acts as a cytokine and binds chromatin that serves as a danger signal following tissue injury (Goodwin et al, 1973; Klune et al, 2008; Scaffidi et al, 2002). Immune cells release this protein (acting as a cytokine), which can bind to TLR4 or the Receptor for Advanced Glycation End products (RAGE) and initiate an inflammatory response (Klune et al, 2008; Parker et al, 2017; Wang et al, 1999). HGMB1 and RAGE are expressed in animals and humans following brain injury (Gao et al, 2012), and inhibition of these pathways reduces BBB breakdown and inflammation (Okuma et al, 2012) as well as pulmonary dysfunction following cerebral contusion (Weber et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Neuroimmunology of Traumatic Brain Injury: Time for a Paradigm Shift

Jassam

Izzy

Whalen

et al. 2017

Neuron

583

496

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SUMMARY Traumatic brain injury (TBI) is a leading cause of morbidity and disability, with a considerable socioeconomic burden. Heterogeneity of pathoanatomical subtypes and diversity in the pathogenesis and extent of injury contribute to differences in the course and outcome of TBI. Following the primary injury, extensive and lasting damage is sustained through a complex cascade of events referred to as “secondary injury”. Neuroinflammation is proposed as an important manipulable aspect of secondary injury in animal and human studies. Because neuroinflammation can be detrimental or beneficial, before developing immunomodulatory therapies, it is necessary to better understand the timing and complexity of the immune responses that follows TBI. With a rapidly increasing body of literature, there is a need for a clear summary of TBI neuroimmunology. This review presents our current understanding of the immune response to TBI in a chronological and compartment-based manner, highlighting early changes in gene expression and initial signaling pathways that lead to activation of innate and adaptive immunity. Based on recent advances in our understanding of innate immune cell activation, we propose a new paradigm to study innate immune cells following TBI that moves away from the existing M1/M2 classification of activation states towards a stimulus and disease-specific understanding of polarization state based on transcriptomic and proteomic profiling.

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The danger zone: Systematic review of the role of HMGB1 danger signalling in traumatic brain injury

Cited by 43 publications

References 20 publications

Commonalities in epileptogenic processes from different acute brain insults: Do they translate?

Commonalities in epileptogenic processes from different acute brain insults: Do they translate?

HMGB1: A Common Biomarker and Potential Target for TBI, Neuroinflammation, Epilepsy, and Cognitive Dysfunction

Neuroimmunology of Traumatic Brain Injury: Time for a Paradigm Shift

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