Inflammation after trauma: Microglial activation and traumatic brain injury

Ramlackhansingh, Anil; Brooks, David J.; Greenwood, Richard; Bose, Subrata K.; Turkheimer, Federico; Kinnunen, Kirsi M.; Gentleman, Steve; Heckemann, Rolf A.; Gunanayagam, Karen; Gelosa, Giorgio; Sharp, David J.

doi:10.1002/ana.22455

Cited by 851 publications

(750 citation statements)

References 30 publications

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“…This deficit may closely relate to the neurodegeneration, which can stem from primary insults as well as the secondary one. Despite the activation of microglia may serve as scavenger, the persistent of this activation can be toxic, which promotes a hostile milieu predisposing to the development of Alzheimer's disease (Ramlackhansingh et al., 2011). The subsequent accumulation of proinflammatory cytokines further aggravates the impairment (Das, Mohapatra, & Mohapatra, 2012).…”

Section: Discussionmentioning

confidence: 99%

Erythropoietin regulates immune/inflammatory reaction and improves neurological function outcomes in traumatic brain injury

Zhou

Zheng

et al. 2017

Brain and Behavior

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IntroductionTraumatic brain injury (TBI) remains a leading cause of disability and death among young people in China. Unfortunately, no specific pharmacological agents to block the progression of secondary brain injury have been approved for clinical treatment. Recently, neuroprotective effects of erythropoietin (EPO) have been demonstrated in addition to its principal function in erythropoiesis, and hence it is viewed as a potential drug for TBI. In this study, we have investigated the neuroprotective effects of EPO associated with immune/inflammatory modulation in a mouse experimental TBI model.Methods EPO (5000 U/kg body weight, i.p.) was injected at 1 hr, 1, 2, and 3 days after TBI, and its effect on cognitive function, brain edema, immune/inflammatory cells including regulatory T cells (Tregs), neutrophils, CD3+ T cells, and microglia, cytokines including interleukin‐10 (IL‐10), transforming growth factor‐β (TGF‐β), interleukin‐1β (IL‐1β), and tumor necrosis factor‐α (TNF‐α) were evaluated at different time points after treatment.Results EPO treatment significantly decreased brain edema and improved cognitive function when compared to Saline‐treated mice (p < .05). EPO treatment also significantly increased Tregs level in spleen and injured brain tissue as well as significantly reduced the infiltration and activation of immune/inflammatory cells (neutrophils, CD3+T cells, and microglia) in the injured hemisphere compared to Saline‐treated control animals (p < .05). In addition, ELISA analysis demonstrated that EPO treatment increased the expression of anti‐inflammatory cytokine IL‐10, but decreased the expression of proinflammatory cytokine IL‐1β and TNF‐α in the injured brain tissue (p < .05).ConclusionsThese findings suggest that EPO could improve neurological and cognitive functional outcomes as well as regulate immune/inflammatory reaction in TBI.

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Section: Discussionmentioning

confidence: 99%

Erythropoietin regulates immune/inflammatory reaction and improves neurological function outcomes in traumatic brain injury

Zhou

Zheng

et al. 2017

Brain and Behavior

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“…18,19 Following TBI, enhanced glial inflammation has been attributed to both white matter dysfunction and cognitive decline, which may be more evident with aging. 20,21 How patterns of axonal injury relate to the cognitive deficits associated with TBI remains to be clarified. Previous investigations of TBI patients with white matter damage have shown neuropsychological deficits in speed of processing, working memory, and attention, without a clear gross structural correlate for these deficits.…”

Section: Introductionmentioning

confidence: 99%

White Matter Changes and Confrontation Naming in Retired Aging National Football League Athletes

Strain

Didehbani

Spence

et al. 2017

Journal of Neurotrauma

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Using diffusion tensor imaging (DTI), we assessed the relationship of white matter integrity and performance on the Boston Naming Test (BNT) in a group of retired professional football players and a control group. We examined correlations between fractional anisotropy (FA) and mean diffusivity (MD) with BNT T-scores in an unbiased voxelwise analysis processed with tract-based spatial statistics (TBSS). We also analyzed the DTI data by grouping voxels together as white matter tracts and testing each tract's association with BNT T-scores. Significant voxelwise correlations between FA and BNT performance were only seen in the retired football players ( p < 0.02). Two tracts had mean FA values that significantly correlated with BNT performance: forceps minor and forceps major. White matter integrity is important for distributed cognitive processes, and disruption correlates with diminished performance in athletes exposed to concussive and subconcussive brain injuries, but not in controls without such exposure.

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“…In addition to the immediate health impacts of the injury, TBI is acknowledged as the strongest environmental risk factor for the development of neurodegenerative disease, typically reported as Alzheimer's disease (AD)(2-13) in type or, more recently, recognized as chronic traumatic encephalopathy (CTE) (14)(15)(16). Corresponding to this, autopsy studies in material from patients exposed to either single moderate or severe or repetitive mild brain injury reveal a complex of neurodegenerative pathologies including pathologies in tau, amyloid-² and TDP-43, neuronal loss, neuroinflammation and white matter degradation (13,(15)(16)(17)(18)(19)(20). However, the mechanisms driving these late, post-TBI neurodegenerative pathologies remain elusive.…”

Section: Introductionmentioning

confidence: 99%

Blood-Brain Barrier Disruption Is an Early Event That May Persist for Many Years After Traumatic Brain Injury in Humans

Hay

Johnson

Young

et al. 2015

Journal of Neuropathology & Experimental Neurology

127

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Traumatic brain injury (TBI) is a risk factor for dementia, with studies describing a mixed neurodegenerative pathology in late survivors. However, the mechanisms driving this post-TBI neurodegeneration remain elusive. Increasingly, blood brain barrier (BBB) disruption is recognized in a range of neurological disorders, including dementias; although little is known of the consequences of TBI on the BBB. From the Glasgow TBI Archive autopsy cases of single, moderate or severe TBI (n=70) were selected to include a range of survivals from acute (10h to 13days) to long-term (1 to 47years) survival, together with age-matched, uninjured controls (n=21). Multiple brain regions were examined for fibrinogen (FBG) and immunoglobulin G (IgG) immunohistochemistry. Following TBI, 40% of patients dying in the acute phase and 47% of those surviving a year or more from injury showed multi-focal, abnormal, perivascular and parenchymal FBG and IgG immunostaining localized to grey matter, with preferential distribution towards the crests of gyri and deep neocortical layers. In contrast, where present, controls showed only limited, localized immunostaining. These preliminary data demonstrate evidence of widespread BBB disruption in a proportion of TBI patients emerging in the acute phase and, intriguingly, persisting in a high proportion of late survivors.

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Inflammation after trauma: Microglial activation and traumatic brain injury

Cited by 851 publications

References 30 publications

Erythropoietin regulates immune/inflammatory reaction and improves neurological function outcomes in traumatic brain injury

Erythropoietin regulates immune/inflammatory reaction and improves neurological function outcomes in traumatic brain injury

White Matter Changes and Confrontation Naming in Retired Aging National Football League Athletes

Blood-Brain Barrier Disruption Is an Early Event That May Persist for Many Years After Traumatic Brain Injury in Humans

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