Brain-gut axis dysfunction in the pathogenesis of traumatic brain injury

Journal of Clinical Investigation, Journal Year: 2021, Volume and Issue: 131(12)

Published: June 14, 2021

Traumatic brain injury (TBI) is a chronic and progressive disease, management requires an understanding of both the primary neurological secondary sequelae that affect peripheral organs, including gastrointestinal (GI) tract. The brain-gut axis composed bidirectional pathways through which TBI-induced neuroinflammation neurodegeneration impact gut function. resulting dysautonomia systemic inflammation contribute to GI events, dysmotility increased mucosal permeability. These effects shape, are shaped by, changes in microbiota composition activation resident recruited immune cells. Microbial products cell mediators turn modulate activity. Importantly, enteric inflammatory challenges prolong worsen neuropathology neurobehavioral deficits. importance communication maintaining homeostasis highlights it as viable therapeutic target for TBI. Currently, treatments directed toward dysautonomia, dysbiosis, and/or offer most promise.

Language: Английский

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Microglia and Neuroinflammation: Crucial Pathological Mechanisms in Traumatic Brain Injury-Induced Neurodegeneration

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: March 25, 2022

Traumatic brain injury (TBI) is one of the most common diseases in central nervous system (CNS) with high mortality and morbidity. Patients TBI usually suffer many sequelae life time post injury, including neurodegenerative disorders such as Alzheimer’s disease (AD) Parkinson’s (PD). However, pathological mechanisms connecting these two processes have not yet been fully elucidated. It important to further investigate pathophysiological underlying TBI-induced neurodegeneration, which will promote development precise treatment target for notorious consequences after TBI. A growing body evidence shows that neuroinflammation a pivotal process chronic neurodegeneration following Microglia, immune cells CNS, play crucial roles other CNS diseases. Of interest, microglial activation functional alteration has proposed key mediators evolution pathology Here, we review updated studies involving phenotypical alterations microglia survey molecules regulating activities responses pathology, explore their potential implications injury. The work give us comprehensive understanding driving TBI-related offer novel ideas developing corresponding prevention strategies this disease.

Language: Английский

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BBB pathophysiology–independent delivery of siRNA in traumatic brain injury

Science Advances, Journal Year: 2021, Volume and Issue: 7(1)

Published: Jan. 1, 2021

We describe a nanoparticle platform for brain delivery of nucleic acid–based therapeutics to treat TBI.

Language: Английский

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The Dialogue Between Neuroinflammation and Adult Neurogenesis: Mechanisms Involved and Alterations in Neurological Diseases

Molecular Neurobiology, Journal Year: 2022, Volume and Issue: 60(2), P. 923 - 959

Published: Nov. 16, 2022

Language: Английский

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ACT001 attenuates microglia-mediated neuroinflammation after traumatic brain injury via inhibiting AKT/NFκB/NLRP3 pathway

Cell Communication and Signaling, Journal Year: 2022, Volume and Issue: 20(1)

Published: April 23, 2022

Abstract Background Microglia-mediated neuroinflammatory response following traumatic brain injury (TBI) is considered as a vital secondary factor, which drives trauma-induced neurodegeneration and lack of efficient treatment. ACT001, sesquiterpene lactone derivative, reportedly involved in alleviation inflammatory response. However, little known regarding its function regulating innate immune central nervous system (CNS) after TBI. This study aimed to investigate the role underlying mechanism ACT001 Methods Controlled cortical impact (CCI) models were used establish model Cresyl violet staining, evans blue extravasation, neurobehavioral assessments, immunofluorescence transmission electron microscopy evaluate therapeutic effects vivo. Microglial depletion was induced by administering mice with colony stimulating factor 1 receptor (CSF1R) inhibitor, PLX5622. Cell-cell interaction established co-culture simulate TBI conditions vitro. Cytotoxic effect on cell viability assessed counting kit-8 activation microglia cells Lipopolysaccharides (LPS). Pro-inflammatory cytokines expression determined Real-time PCR nitric oxide production. Apoptotic detected TUNEL flow cytometry assays. Tube formation performed cellular angiogenic ability. ELISA western blot experiments determine proteins expression. Pull-down assay analyze that bound ACT001. Results relieved extent blood-brain barrier integrity damage alleviated motor deficits via reducing cells. Delayed PLX5622 hindered Furthermore, LPS-induced mouse rat primary Besides, effective suppressing pro-inflammatory production BV2 cells, resulting reduction neuronal apoptosis HT22 improvement tube bEnd.3 Mechanism functioned related AKT/NFκB/NLRP3 pathway. restrained NFκB nuclear translocation through inhibiting AKT phosphorylation, decrease NLRP3 inflammasome activation, finally down-regulated microglial Conclusions Our indicated played critical microglia-mediated might be novel potential chemotherapeutic drug for

Language: Английский

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