Hepatic alterations are accompanied by changes to bile acid transporter-expressing neurons in the hypothalamus after traumatic brain injury

Nizamutdinov, Damir; DeMorrow, Sharon; McMillin, Matthew; Kain, Jessica; Mukherjee, Sumitava; Zeitouni, Suzanne; Frampton, Gabriel; Bricker, Paul Clint S.; Hurst, Jacob; Shapiro, Lee A.

doi:10.1038/srep40112

Cited by 35 publications

(26 citation statements)

References 77 publications

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“…TBI-derived cytokines trigger an early remote hepatic acute-phase response that produces ‘CC’ and ‘CXC’ chemokines and recruits leukocytes to the liver and damaged brain areas 142 . Furthermore, alterations to the homeostasis of hepatic and brain bile acid add to the systemic inflammation and neurological dysfunction 143 . After injury to the central nervous system, liver Kupffer cells mainly control the influx of neutrophils into remote sites of injury but contribute only partially to the full hepatic inflammatory response 144 .…”

Section: Cerebral and Extracerebral Challenges To The Innate Immune Smentioning

confidence: 99%

Innate immune responses to trauma

2018

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Trauma can affect any individual at any location and at any time over a lifespan. The disruption of macrobarriers and microbarriers induces instant activation of innate immunity. The subsequent complex response, designed to limit further damage and induce healing, also represents a major driver of complications and fatal outcome after injury. This Review aims to provide basic concepts about the posttraumatic response and is focused on the interactive events of innate immunity at frequent sites of injury: the endothelium at large, and sites within the lungs, inside and outside the brain and at the gut barrier.

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Section: Cerebral and Extracerebral Challenges To The Innate Immune Smentioning

confidence: 99%

Innate immune responses to trauma

2018

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“…36 Identification of the mechanism(s) of action by which bile acids may alter the neurological function in mice with acute liver failure began with the demonstration of bile acid transporter, ASBT, expression, which co-localized with neuronal markers in various brain regions, including the frontal cortex, 11,36 and has been confirmed in other models of neurological disorders. 40 In vitro, the uptake of a fluorescent bile acid derivative, cholyl-lysyl fluorescein, into neurons was inhibited by the specific knockdown of ASBT expression. 11 Once inside the neuron, it is hypothesized that bile acids are exerting their effects through the activation of FXR.…”

Section: Effect Of Bile Acids On Neuronal Dysfunctionmentioning

confidence: 99%

Bile Acids in Hepatic Encephalopathy

DeMorrow

2019

Journal of Clinical and Experimental Hepatology

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TX 76504, USA and y Central Texas Veterans Healthcare System, Temple, TX 76504, USA Hepatic encephalopathy describes the array of neurological complications that arise due to liver insufficiency and/or portal-systemic shunt. The pathogenesis of hepatic encephalopathy shares a longstanding association with hyperammonemia and inflammation. Recently, aberrant bile acid signaling has been implicated in the development of key features of hepatic encephalopathy due to acute liver failure including neuronal dysfunction, neuroinflammation and blood-brain barrier permeability. This review summarizes the findings of recent studies demonstrating a role for bile acids in hepatic encephalopathy and speculates on the possible downstream consequences of bile acid signaling. ( J CLIN EXP HEPATOL 2019;9:117-124) Keywords: blood-brain barrier, farnesoid X receptor, neuroinflammation, sphingosine-1-phosphate receptor 2, Takeda G-protein coupled receptor 5 (TGR5)

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“…Another group displayed significant bile acid signaling in a TBI animal model. A significant decrease in ASBT-expressing neurons was observed in the hypothalamus of a rodent model of TBI, which could adversely contribute to inflammatory responses [ 135 ].…”

Section: Neurological Disorders and Bile Acidsmentioning

confidence: 99%

Bile Acid Signaling in Neurodegenerative and Neurological Disorders

Grant

DeMorrow

2020

IJMS

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107

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Bile acids are commonly known as digestive agents for lipids. The mechanisms of bile acids in the gastrointestinal track during normal physiological conditions as well as hepatic and cholestatic diseases have been well studied. Bile acids additionally serve as ligands for signaling molecules such as nuclear receptor Farnesoid X receptor and membrane-bound receptors, Takeda G-protein-coupled bile acid receptor and sphingosine-1-phosphate receptor 2. Recent studies have shown that bile acid signaling may also have a prevalent role in the central nervous system. Some bile acids, such as tauroursodeoxycholic acid and ursodeoxycholic acid, have shown neuroprotective potential in experimental animal models and clinical studies of many neurological conditions. Alterations in bile acid metabolism have been discovered as potential biomarkers for prognosis tools as well as the expression of various bile acid receptors in multiple neurological ailments. This review explores the findings of recent studies highlighting bile acid-mediated therapies and bile acid-mediated signaling and the roles they play in neurodegenerative and neurological diseases.

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Hepatic alterations are accompanied by changes to bile acid transporter-expressing neurons in the hypothalamus after traumatic brain injury

Cited by 35 publications

References 77 publications

Innate immune responses to trauma

Innate immune responses to trauma

Bile Acids in Hepatic Encephalopathy

Bile Acid Signaling in Neurodegenerative and Neurological Disorders

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