Traumatic brain injury: progress and challenges in prevention, clinical care, and research

The Lancet Neurology, Journal Year: 2022, Volume and Issue: 21(11), P. 1004 - 1060

Published: Sept. 29, 2022

Language: Английский

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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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Brain–lung interactions and mechanical ventilation in patients with isolated brain injury

Critical Care, Journal Year: 2021, Volume and Issue: 25(1)

Published: Oct. 13, 2021

Abstract During the last decade, experimental and clinical studies have demonstrated that isolated acute brain injury (ABI) may cause severe dysfunction of peripheral extracranial organs systems. Of all potential target systems, lung appears to be most vulnerable damage after (BI). The pathophysiology these brain–lung interactions are complex involve neurogenic pulmonary oedema, inflammation, neurodegeneration, neurotransmitters, immune suppression autonomic system. systemic effects inflammatory mediators in patients with BI create a environment makes secondary procedures enhance such as mechanical ventilation (MV), surgery infections. Indeed, previous shown presence environment, specific neurointensive care interventions—such MV—may significantly contribute development injury, regardless underlying mechanisms. Although current knowledge supports protective BI, it must born mind ABI-related has distinct mechanisms between lungs. In this context, role extracerebral pathophysiology, especially lungs, often been overlooked, physicians focus on intracranial cerebral dysfunction. present review aims fill gap by describing complications due injuries single ABI, discusses possible impact MV neurocritical normal

Language: Английский

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Enhancement of the liver’s neuroprotective role ameliorates traumatic brain injury pathology

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(26)

Published: June 20, 2023

Traumatic brain injury (TBI) is a pervasive problem worldwide for which no effective treatment currently available. Although most studies have focused on the pathology of injured brain, we noted that liver plays an important role in TBI. Using two mouse models TBI, found enzymatic activity hepatic soluble epoxide hydrolase (sEH) was rapidly decreased and then returned to normal levels following whereas such changes were not observed kidney, heart, spleen, or lung. Interestingly, genetic downregulation Ephx2 (which encodes sEH) ameliorates TBI-induced neurological deficits promotes function recovery, overexpression sEH exacerbates TBI-associated impairments. Furthermore, ablation promote generation A2 phenotype astrocytes facilitate production various neuroprotective factors associated with We also inverted V-shaped alteration plasma four EET (epoxyeicosatrienoic acid) isoforms (5,6-, 8,9-,11,12-, 14,15-EET) TBI negatively correlated activity. However, manipulation bidirectionally regulates 14,15-EET, crosses blood–brain barrier. Additionally, application 14,15-EET mimicked effect ablation, while 14,15-epoxyeicosa-5(Z)-enoic acid blocked this effect, indicating increased mediated after ablation. These results highlight suggest targeting signaling could represent promising therapeutic strategy treating

Language: Английский

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Dysregulated brain-gut axis in the setting of traumatic brain injury: review of mechanisms and anti-inflammatory pharmacotherapies

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: May 10, 2024

Abstract Traumatic brain injury (TBI) is a chronic and debilitating disease, associated with high risk of psychiatric neurodegenerative diseases. Despite significant advancements in improving outcomes, the lack effective treatments underscore urgent need for innovative therapeutic strategies. The brain-gut axis has emerged as crucial bidirectional pathway connecting gastrointestinal (GI) system through an intricate network neuronal, hormonal, immunological pathways. Four main pathways are primarily implicated this crosstalk, including systemic immune system, autonomic enteric nervous systems, neuroendocrine microbiome. TBI induces profound changes gut, initiating unrestrained vicious cycle that exacerbates axis. Alterations gut include mucosal damage malabsorption nutrients/electrolytes, disintegration intestinal barrier, increased infiltration cells, dysmotility, dysbiosis, enteroendocrine cell (EEC) dysfunction disruption (ENS) (ANS). Collectively, these further contribute to neuroinflammation neurodegeneration via gut-brain In review article, we elucidate roles various anti-inflammatory pharmacotherapies capable attenuating dysregulated inflammatory response along TBI. These agents hormones such serotonin, ghrelin, progesterone, ANS regulators beta-blockers, lipid-lowering drugs like statins, flora modulators probiotics antibiotics. They attenuate by targeting distinct both post-TBI. exhibit promising potential mitigating inflammation enhancing neurocognitive outcomes patients.

Language: Английский

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Pathophysiology of acute lung injury in patients with acute brain injury: the triple-hit hypothesis

Critical Care, Journal Year: 2024, Volume and Issue: 28(1)

Published: March 7, 2024

Abstract It has been convincingly demonstrated in recent years that isolated acute brain injury (ABI) may cause severe dysfunction of peripheral extracranial organs and systems. Of all potential target systems, the lung appears to be most vulnerable damage after ABI. The pathophysiology bidirectional brain–lung interactions is multifactorial involves inflammatory cascades, immune suppression, autonomic system. Indeed, systemic effects mediators patients with ABI create a environment (“first hit”) makes secondary procedures enhance inflammation, such as mechanical ventilation (MV), surgery, infections (“second hit”). Moreover, accumulating evidence supports knowledge gut microbiota constitutes critical superorganism an organ on its own, potentially modifying various physiological functions host. Furthermore, experimental clinical data suggest existence communication network among brain, gastrointestinal tract, microbiome, which regulate responses, function, behavior, stress also named “gut-microbiome–brain axis.” Additionally, research highlighted crucial interplay between intestinal lungs, referred “gut-lung axis,” alterations during illness could result bacterial translocation, sustained injury, pulmonary fibrosis. In present work, we aimed further elucidate (ALI) by attempting develop “double-hit” theory, proposing “triple-hit” hypothesis, focused influence gut–lung axis lung. Particularly, propose, addition sympathetic hyperactivity, blast double-hit dysbiosis context alter axis, resulting development or aggravation existing ALI, “third hit.”

Language: Английский

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Crosstalk of Brain and Bone—Clinical Observations and Their Molecular Bases

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(14), P. 4946 - 4946

Published: July 13, 2020

As brain and bone disorders represent major health issues worldwide, substantial clinical investigations demonstrated a bidirectional crosstalk on several levels, mechanistically linking both apparently unrelated organs. While multiple stress, mood neurodegenerative are associated with osteoporosis, rare genetic skeletal diseases display impaired development function. Along pathologies, particularly trauma events highlight the strong interaction of This review summarizes experimental observations reported for bone, followed by detailed overview their molecular bases. brain-derived molecules affecting include central regulators, transmitters sympathetic, parasympathetic sensory nervous system, bone-derived mediators altering function released from cells marrow. Although main pathways brain-bone remain ‘efferent’, signaling to this emphasizes emergence as crucial ‘afferent’ regulator cerebral development, pathophysiology. Therefore, unraveling physiological pathological bases interactions revealed promising pharmacologic targets novel treatment strategies promoting concurrent recovery.

Language: Английский

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Biomimetic Nanoparticles as a Theranostic Tool for Traumatic Brain Injury

Advanced Functional Materials, Journal Year: 2021, Volume and Issue: 31(30)

Published: March 26, 2021

Traumatic brain injury (TBI) triggers both central and peripheral inflammatory responses. Existing pharmacological drugs are unable to effectively quickly target the inflamed regions, setting up a major roadblock towards effective trauma treatments. Nanoparticles (NPs) have been used in multiple diseases as drug delivery tools with remarkable success due their rapid diffusion specificity organ. Here, leukocyte-based biomimetic NPs fabricated theranostic tool directly access regions TBI mouse model. This NP systemic is visualized using advanced vivo imaging techniques, including intravital microscopy system. The results demonstrate selective targeting of injured increased accumulation among organs 24 h after TBI. Interestingly, microglial proliferation, decreased macrophage infiltration, reduced lesion following treatments compared sham vehicle-treated mice also found. In summary, suggest that represent promising future for treatment.

Language: Английский

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The Immune System's Role in the Consequences of Mild Traumatic Brain Injury (Concussion)

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Feb. 15, 2021

Mild traumatic brain injury (mild TBI), often referred to as concussion, is the most common form of TBI and affects millions people each year. A history mild increases risk developing emotional neurocognitive disorders later in life that can impact on day living. These include anxiety depression, well neurodegenerative conditions such chronic encephalopathy (CTE) Alzheimer's disease (AD). Actions resident or peripherally recruited immune cells are proposed be key regulators across these diseases mood disorders. Here, we will assess patient health, evaluate recent evidence for cell involvement its pathogenesis.

Language: Английский

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Multiorgan Dysfunction After Severe Traumatic Brain Injury

CHEST Journal, Journal Year: 2021, Volume and Issue: 160(3), P. 956 - 964

Published: Jan. 17, 2021

Language: Английский

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