Ischemic stroke induces gut permeability and enhances bacterial translocation leading to sepsis in aged mice

Crapser, Joshua; Ritzel, Rodney M.; Verma, Rajkumar; Venna, Venugopal Reddy; Liu, Fudong; Chauhan, Anjali; Koellhoffer, Edward C.; Patel, Anita; Ricker, Austin; Maas, Kendra; Graf, Joerg; McCullough, Louise D.

doi:10.18632/aging.100952

Cited by 154 publications

(141 citation statements)

References 49 publications

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“…Bacterial metabolites can diffuse into the circulation and act in an endocrine role to signal distant targets such as the brain . Additionally, stroke in young and aged animals increases the permeability of the gut wall allowing for the translocation of bacteria and bacterial components (toxins and bacterial proteins) to produce, initiate, or enhance regional and systemic inflammation …”

Section: Discussionmentioning

confidence: 99%

Age‐related changes in the gut microbiota influence systemic inflammation and stroke outcome

Spychala

Venna

Jandzinski

et al. 2018

Annals of Neurology

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323

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Section: Discussionmentioning

confidence: 99%

Age‐related changes in the gut microbiota influence systemic inflammation and stroke outcome

Spychala

Venna

Jandzinski

et al. 2018

Annals of Neurology

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340

323

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“…In mice subjected to transient focal cerebral ischemia, trafficking of intestinal T cells from the gut to the meninges of the brain increases neuroinflammation and the secretion of pro-inflammatory cytokine IL-17; which can stimulate the production of several other cytokines and chemokines and facilitate the infiltration of cytotoxic immune cells and neutrophils into the injured brain 130 . In mice subjected to transient focal cerebral ischemia, stroke increased gut permeability proportional to stroke severity, promoted bacterial translocation from the gut to mesenteric lymph nodes and peripheral organs such as spleen, liver and lungs, as well as triggered adaptive and innate immune responses 135 . In ischemic stroke patients, gut dysbiosis and increased bacterial counts of Lactobacillus ruminis subgroup in the fecal gut microbiota was associated with elevated systemic inflammation and altered metabolism 136 .…”

Section: Mechanisms Of Brain-heart Interaction After Strokementioning

confidence: 99%

Brain–Heart Interaction

Chen

Venkat

Seyfried

et al. 2017

Circulation Research

417

202

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Neurocardiology is an emerging specialty that addresses the interaction between the brain and the heart, i.e. the effects of cardiac injury on the brain, and the effects of brain injury on the heart. This review article focuses on cardiac dysfunction in the setting of stroke such as ischemic stroke, brain hemorrhage and subarachnoid hemorrhage (SAH). The majority of post stroke deaths are attributed to neurological damage, and cardiovascular complications are the second leading cause of post stroke mortality. Accumulating clinical and experimental evidence suggests a causal relationship between brain damage and heart dysfunction. Thus, it is important to determine whether cardiac dysfunction is triggered by stroke, is an unrelated complication, or is the underlying cause of stroke. Stroke induced cardiac damage may lead to fatality or potentially lifelong cardiac problems (such as heart failure), or to mild and recoverable damage such as neurogenic stress cardiomyopathy (NSC) and Takotsubo cardiomyopathy. The role of location and lateralization of brain lesions after stroke in brain-heart interaction, clinical biomarkers and manifestations of cardiac complications, and underlying mechanisms of brain-heart interaction following stroke, such as: the hypothalamic pituitary adrenal axis (HPA); catecholamine surge; sympathetic and parasympathetic regulation; microvesicles (MV’s); microRNAs; gut microbiome, immunoresponse and systemic inflammation are discussed.

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“…Preclinical data from experimental models of ischemic stroke report direct evidence of intestinal barrier dysfunction, which leads to 'bacterial translocation' [130][131][132] . Bacterial translocation can be defined as the invasion of indigenous bacteria or endotoxins across the gut mucosa and into the circulation causing systemic inflammation and distant organ injury 133 .…”

Section: Closing the Loop: Insights From Acute Cerebral Ischemic Eventsmentioning

confidence: 99%

The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease

Sundman

Chen

Subbian

et al. 2017

Brain, Behavior, and Immunity

155

103

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The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease. AbstractAs head injuries and their sequelae have become an increasingly salient matter of public health, experts in the field have made great progress elucidating the biological processes occurring within the brain at the moment of injury and throughout the recovery thereafter. Given the extraordinary rate at which our collective knowledge of neurotrauma has grown, new insights may be revealed by examining the existing literature across disciplines with a new perspective. This article will aim to expand the scope of this rapidly evolving field of research beyond the confines of the central nervous system (CNS). Specifically, we will examine the extent to which the bidirectional influence of the gut-brain axis modulates the complex biological processes occurring at the time of traumatic brain injury (TBI) and over the days, months, and years that follow. In addition to local enteric signals originating in the gut, it is well accepted that gastrointestinal (GI) physiology is highly regulated by innervation from the CNS. Conversely, emerging data suggests that the function and health of the CNS is modulated by the interaction between 1) neurotransmitters, immune signaling, hormones, and neuropeptides produced in the gut, 2) the composition of the gut microbiota, and 3) integrity of the intestinal wall serving as a barrier to the external environment. Specific to TBI, existing pre-clinical data indicates that head injuries can cause structural and functional damage to the GI tract, but research directly investigating the neuronal consequences of this intestinal damage is lacking. Despite this void, the proposed mechanisms emanating from a damaged gut are closely implicated in the inflammatory processes known to promote neuropathology in the brain following TBI, which suggests the gut-brain axis may be a therapeutic target to reduce the risk of Chronic Traumatic Encephalopathy and other neurodegenerative diseases following TBI. To better appreciate how various peripheral influences are implicated in the health of the CNS following TBI, this paper will also review the secondary biological injury mechanisms and the dynamic pathophysiological response to neurotrauma. Together, this review article will attempt to connect the dots to reveal novel insights into the bidirectional influence of the gut-brain axis and propose a conceptual model relevant to the recovery from TBI and subsequent risk for future neurological conditions.

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Ischemic stroke induces gut permeability and enhances bacterial translocation leading to sepsis in aged mice

Cited by 154 publications

References 49 publications

Age‐related changes in the gut microbiota influence systemic inflammation and stroke outcome

Age‐related changes in the gut microbiota influence systemic inflammation and stroke outcome

Brain–Heart Interaction

The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease

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