Hydroxychloroquine attenuates neuroinflammation following traumatic brain injury by regulating the TLR4/NF-κB signaling pathway

Journal of Neuroinflammation, Journal Year: 2022, Volume and Issue: 19(1)

Published: March 28, 2022

After traumatic brain injury (TBI), an acute, robust inflammatory cascade occurs that is characterized by the activation of resident cells such as microglia, migration and recruitment peripheral immune release mediators induce secondary cell death impede neurological recovery. In addition, neuroinflammation can alter blood-brain barrier (BBB) permeability. Controlling responses considered a promising therapeutic approach for TBI. Hydroxychloroquine (HCQ) has already been used clinically decades, it still widely to treat various autoimmune diseases. However, effects HCQ on inflammation potential mechanism after TBI remain be defined. The aim current study was elucidate whether could improve recovery mice post-TBI inhibiting response via TLR4/NF-κB signaling pathway.C57BL/6 were subjected controlled cortical impact (CCI) randomly divided into groups received intraperitoneal or vehicle daily TAK-242 (3.0 mg/kg), exogenous TLR4 antagonist, injected intraperitoneally 1 h before Behavioral assessments performed days 3 post-TBI, gene expression levels cytokines analyzed qRT-PCR. presence infiltrated examined flow cytometry immunostaining. BBB permeability, tight junction edema investigated.HCQ administration significantly ameliorated TBI-induced deficits. alleviated neuroinflammation, accumulation microglia infiltration in brain, attenuated disruption edema, upregulated expression. Combined did not enhance neuroprotective HCQ.HCQ reduced proinflammatory cytokine expression, underlying may involve suppressing pathway, suggesting agent treatment.

Language: Английский

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Inflammatory Biomarkers of Traumatic Brain Injury

Pharmaceuticals, Journal Year: 2022, Volume and Issue: 15(6), P. 660 - 660

Published: May 25, 2022

Traumatic brain injury (TBI) has a complex pathology in which the initial releases damage associated proteins that exacerbate neuroinflammatory response during chronic secondary period. One of major pathological players inflammatory after TBI is inflammasome. Increased levels inflammasome acute phase are with worse functional outcomes. Previous studies reveal level biological fluids may be used as promising new biomarkers for determination In this study, we provide further evidence cytokines and serum to determine severity predict analyzed blood from patients respective controls utilizing Simple Plex V-PLEX cytokine assays. We performed statistical analyses were significantly elevated individuals. The receiver operating characteristics (ROC) determined obtain area under curve (AUC) establish potential fit biomarker. Potential then compared documented patient Glasgow coma scale scores via correlation matrix multivariate linear regression how related outcome. Inflammasome TBI, apoptosis-associated speck like protein containing caspase recruitment domain (ASC), interleukin (IL)-18, tumor necrosis factor (TNF)-α, IL-4 IL-6 most reliable biomarkers. Additionally, these correlated known clinical indicators outcome, such (GCS). Our results show determining outcomes TBI. could potentially utilized patient's subsequent These findings inflammation-associated can also assess patients.

Language: Английский

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The potential for treg-enhancing therapies in nervous system pathologies

Clinical & Experimental Immunology, Journal Year: 2022, Volume and Issue: 211(2), P. 108 - 121

Published: Aug. 30, 2022

Summary While inflammation may not be the cause of disease, it is well known that contributes to disease pathogenesis across a multitude peripheral and central nervous system disorders. Chronic overactive due an effector T-cell-mediated aberrant immune response ultimately leads tissue damage neuronal cell death. To counteract neuroinflammatory responses, research being focused on regulatory T enhancement as therapeutic target. Regulatory cells are immunosuppressive subpopulation CD4+ helper essential for maintaining homeostasis. The play pivotal roles in suppressing responses maintain tolerance. In so doing, they control proliferation pro-inflammatory cytokine production curtailing autoimmunity inflammation. For pathologies, Treg affect onset tempo neural injuries. this end, we review recent findings supporting Treg’s role serving agent multiple sclerosis, myasthenia gravis, Guillain–Barre syndrome, Parkinson’s Alzheimer’s diseases, amyotrophic lateral sclerosis. An ever-broader neurologic has been shown traumatic brain injury, stroke, neurotrophic pain, epilepsy, psychiatric such ends, serves examine played by Tregs diseases with focus harnessing their functional role(s).

Language: Английский

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Wireless charging-mediated angiogenesis and nerve repair by adaptable microporous hydrogels from conductive building blocks

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Sept. 2, 2022

Abstract Traumatic brain injury causes inflammation and glial scarring that impede tissue repair, so stimulating angiogenesis recovery of function remain challenging. Here we present an adaptable conductive microporous hydrogel consisting gold nanoyarn balls-coated injectable building blocks possessing interconnected pores to improve in traumatic injury. We show following minimally invasive implantation, the is able fill defects with complex shapes regulate environment a mouse model. find placement this at peri-trauma regions enhances mature brain-derived neurotrophic factor by 180% improves 250% vivo within 2 weeks after electromagnetized stimulation, these effects facilitate neuron survival motor 50%. use blood oxygenation level-dependent functional neuroimaging reveal successful restoration connectivity corticostriatal corticolimbic circuits.

Language: Английский

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IL-12 sensing in neurons induces neuroprotective CNS tissue adaptation and attenuates neuroinflammation in mice

Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(10), P. 1701 - 1712

Published: Sept. 25, 2023

Abstract Interleukin-12 (IL-12) is a potent driver of type 1 immunity. Paradoxically, in autoimmune conditions, including the CNS, IL-12 reduces inflammation. The underlying mechanism behind these opposing properties and involved cellular players remain elusive. Here we map receptor (IL-12R) expression to NK T cells as well neurons oligodendrocytes. Conditionally ablating IL-12R across cell types adult mice assessing their susceptibility experimental encephalomyelitis revealed that neuroprotective role mediated by neuroectoderm-derived cells, specifically neurons, not immune cells. In human brain tissue from donors with multiple sclerosis, observe an distribution comparable mice, suggesting similar mechanisms humans. Combining flow cytometry, bulk single-nucleus RNA sequencing, reveal IL-12-induced adaption preventing early neurodegeneration sustaining trophic factor release during neuroinflammation, thereby maintaining CNS integrity mice.

Language: Английский

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