S100B Inhibition Reduces Behavioral and Pathologic Changes in Experimental Traumatic Brain Injury

Kabadi, Shruti V.; Stoica, Bogdan A.; Zimmer, Danna B.; Afanador, Lauriaselle; Duffy, Kara B.; Loane, David J.; Faden, Alan I.

doi:10.1038/jcbfm.2015.165

Cited by 43 publications

(34 citation statements)

References 41 publications

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“…These authors reported an association between serum S100B and the diffusion tensor imaging parameters fractional anisotropy and radial diffusivity in white matter tracts in healthy females. From the biological point of view increased secretion of S100B might reflect neuroinflammation that accompanies neuronal damage (Kabadi et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

First Evidence For Glial Pathology In Late Life Minor Depression: s100b Is Increased In Males With Minor Depression

et al. 2016

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Minor depression is diagnosed when a patient suffers from 2 to 4 depressive symptoms for at least 2 weeks. Though minor depression is a widespread phenomenon, its pathophysiology has hardly been studied. To get a first insight into the pathophysiological mechanisms underlying this disorder we assessed serum levels of biomarkers for plasticity, glial and neuronal function: brain-derived neurotrophic factor (BDNF), S100B and neuron specific enolase (NSE). 27 subjects with minor depressive episode and 82 healthy subjects over 60 years of age were selected from the database of the Leipzig population-based study of civilization diseases (LIFE). Serum levels of BDNF, S100B and NSE were compared between groups, and correlated with age, body-mass index (BMI), and degree of white matter hyperintensities (score on Fazekas scale). S100B was significantly increased in males with minor depression in comparison to healthy males, whereas other biomarkers did not differ between groups (p = 0.10-0.66). NSE correlated with Fazekas score in patients with minor depression (r s = 0.436, p = 0.048) and in the whole sample (r s = 0.252, p = 0.019). S100B correlated with BMI (r s = 0.246, p = 0.031) and with age in healthy subjects (r s = 0.345, p = 0.002). Increased S100B in males with minor depression, without alterations in BDNF and NSE, supports the glial hypothesis of depression. Correlation between white matter hyperintensities and NSE underscores the vascular hypothesis of late life depression.

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Section: Discussionmentioning

confidence: 99%

First Evidence For Glial Pathology In Late Life Minor Depression: s100b Is Increased In Males With Minor Depression

et al. 2016

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“…However, some studies predicted neuroprotective role of S100B [120]; thus, the verdict regarding beneficial or detrimental role of S100B in PD remains open. S100B level is also higher in the brain and blood of patients suffering from epilepsy and TBI [121, 122]. Due to the constant elevation of S100B in the serum of neuroinflammatory conditions with compromised BBB, it is considered as a marker of BBB integrity [123, 124].…”

Section: Damage-associated Molecular Patternsmentioning

confidence: 99%

Sterile Neuroinflammation and Strategies for Therapeutic Intervention

Banjara

Ghosh

2017

International Journal of Inflammation

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Sterile neuroinflammation is essential for the proper brain development and tissue repair. However, uncontrolled neuroinflammation plays a major role in the pathogenesis of various disease processes. The endogenous intracellular molecules so called damage-associated molecular patterns or alarmins or damage signals that are released by activated or necrotic cells are thought to play a crucial role in initiating an immune response. Sterile inflammatory response that occurs in Alzheimer's disease (AD), Parkinson's disease (PD), stroke, hemorrhage, epilepsy, or traumatic brain injury (TBI) creates a vicious cycle of unrestrained inflammation, driving progressive neurodegeneration. Neuroinflammation is a key mechanism in the progression (e.g., AD and PD) or secondary injury development (e.g., stroke, hemorrhage, stress, and TBI) of multiple brain conditions. Hence, it provides an opportunity for the therapeutic intervention to prevent progressive tissue damage and loss of function. The key for developing anti-neuroinflammatory treatment is to minimize the detrimental and neurotoxic effects of inflammation while promoting the beneficial and neurotropic effects, thereby creating ideal conditions for regeneration and repair. This review outlines how inflammation is involved in the pathogenesis of major nonpathogenic neuroinflammatory conditions and discusses the complex response of glial cells to damage signals. In addition, emerging experimental anti-neuroinflammatory drug treatment strategies are discussed.

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“…As extracranial sources of S100β do not affect serum levels in humans [122], reduced tissue expression likely reflects increased extracellular release due to pathological conditions [111]. Functionally, S100β inhibition reduced neurodegeneration [123] and S100β −/− mice or antibody-mediated neutralization of S100β attenuated microglial reactivity and improved memory function after experimental TBI [124]. Thus, S100β may represent a predictive biomarker of outcomes and target for therapeutic development after TBI [125].…”

Section: Damage Associated Molecular Patterns (Damps): Mediators Omentioning

confidence: 99%

White matter damage after traumatic brain injury: A role for damage associated molecular patterns

Braun

Vaibhav

Saad

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Traumatic brain injury (TBI) is a leading cause of mortality and long-term morbidity worldwide. Despite decades of pre-clinical investigation, therapeutic strategies focused on acute neuroprotection failed to improve TBI outcomes. This lack of translational success has necessitated a reassessment of the optimal targets for intervention, including a heightened focus on secondary injury mechanisms. Chronic immune activation correlates with progressive neurodegeneration for decades after TBI; however, significant challenges remain in functionally and mechanistically defining immune activation after TBI. In this review, we explore the burgeoning evidence implicating the acute release of damage associated molecular patterns (DAMPs), such as adenosine 5′-triphosphate (ATP), high mobility group box protein 1 (HMGB1), S100 proteins, and hyaluronic acid in the initiation of progressive neurological injury, including white matter loss after TBI. The role that pattern recognition receptors, including toll-like receptor and purinergic receptors, play in progressive neurological injury after TBI is detailed. Finally, we provide support for the notion that resident and infiltrating macrophages are critical cellular targets linking acute DAMP release with adaptive immune responses and chronic injury after TBI. The therapeutic potential of targeting DAMPs and barriers to clinical translational, in the context of TBI patient management, are discussed.

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S100B Inhibition Reduces Behavioral and Pathologic Changes in Experimental Traumatic Brain Injury

Cited by 43 publications

References 41 publications

First Evidence For Glial Pathology In Late Life Minor Depression: s100b Is Increased In Males With Minor Depression

First Evidence For Glial Pathology In Late Life Minor Depression: s100b Is Increased In Males With Minor Depression

Sterile Neuroinflammation and Strategies for Therapeutic Intervention

White matter damage after traumatic brain injury: A role for damage associated molecular patterns

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