Chemokine signaling mediated monocyte infiltration affects anxiety-like behavior following blast injury

Murugan, Madhuvika; Ravula, Arunreddy; Gandhi, Ajay; Vegunta, Geetasravya; A., Mukkamalla, Sushni, Amundson, Ashley, Curry, Michael; Mujib, Waleed; Chandra, Namas

doi:10.1016/j.bbi.2020.03.029

Cited by 27 publications

(19 citation statements)

References 65 publications

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“…Other studies as well as our own also observed ethanol induced microglial activation [24,[52][53][54]. Expectedly, the combination likewise caused microglia activation and greater numbers to gather at sites with RBC aggregation (Fig.…”

Section: Implied Microglial Phagocytosissupporting

confidence: 74%

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Hemolytic Iron Regulation in Traumatic Brain Injury and Alcohol Use

Agas

Ravula

et al. 2022

Preprint

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Hemorrhage is often a major component of traumatic brain injury (TBI). Red blood cells (RBCs), accumulated at the hemorrhagic site, undergo hemolysis upon energy depletion. Hemolysis of RBCs is expected to release free iron into the central nervous system (CNS) which must be managed to prevent iron neurotoxicity. Here, we examine the hypothesis that chronic alcohol consumption, as a secondary stressor, may increase iron toxicity in a rat model of TBI by altering the iron management pathways. We found large accumulations of free iron at the site of hemorrhage with evidence of hemolytic activity. Our observations demonstrate that alcohol use can alter the three distinct iron management pathways: transferrin/hemosiderin binding, lipocalin 2/heme oxygenase 1/ferritin system, and possible microglial phagocytosis. Presence of alcohol prolonged the expression of lipocalin 2 as well as increased and sustained levels of ferritin, while the combined effects of alcohol and TBI elevated the levels of heme oxygenase 1 faster than TBI alone. The hippocampus, neocortex, ventricles, and around vessels near the site of impact appeared to be the prominent brain regions of induction. In addition, we provide evidence that microglia my also play a role in iron management through RBC phagocytosis.

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Section: Implied Microglial Phagocytosissupporting

confidence: 74%

“…Many studies have already shown that traumatic brain injury activates microglia [23]. Microglia become activated after transitioning through a series of activation states [24]. During this time, microglia undergo changes in both morphology and function.…”

Section: Introductionmentioning

confidence: 99%

Hemolytic Iron Regulation in Traumatic Brain Injury and Alcohol Use

Agas

Ravula

et al. 2022

Preprint

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“…Moreover, MMP-2 and MMP-9 activity become stronger at the parenchymal border, which speeds up peripheral leukocyte migration through the BBB by decomposing the BM and glia limitans ( 76 ). In a traumatic brain model, compromised BBB permeability and CCL2 chemotaxis facilitated monocyte penetration through the BBB, which resulted in aberrant emotional activity and temporary memory deficiency ( 77 ).…”

Section: Chronic Inflammation Bbb Disruption and Nfandndmentioning

confidence: 99%

Gut Microbiota Interact With the Brain Through Systemic Chronic Inflammation: Implications on Neuroinflammation, Neurodegeneration, and Aging

Mou¹,

Zhou

et al. 2022

Front. Immunol.

165

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It has been noticed in recent years that the unfavorable effects of the gut microbiota could exhaust host vigor and life, yet knowledge and theory are just beginning to be established. Increasing documentation suggests that the microbiota–gut–brain axis not only impacts brain cognition and psychiatric symptoms but also precipitates neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). How the blood–brain barrier (BBB), a machinery protecting the central nervous system (CNS) from the systemic circulation, allows the risky factors derived from the gut to be translocated into the brain seems paradoxical. For the unique anatomical, histological, and immunological properties underpinning its permeable dynamics, the BBB has been regarded as a biomarker associated with neural pathogenesis. The BBB permeability of mice and rats caused by GM dysbiosis raises the question of how the GM and its metabolites change BBB permeability and causes the brain pathophysiology of neuroinflammation and neurodegeneration (NF&ND) and brain aging, a pivotal multidisciplinary field tightly associated with immune and chronic systemic inflammation. If not all, gut microbiota-induced systemic chronic inflammation (GM-SCI) mainly refers to excessive gut inflammation caused by gut mucosal immunity dysregulation, which is often influenced by dietary components and age, is produced at the interface of the intestinal barrier (IB) or exacerbated after IB disruption, initiates various common chronic diseases along its dispersal routes, and eventually impairs BBB integrity to cause NF&ND and brain aging. To illustrate the immune roles of the BBB in pathophysiology affected by inflammatory or “leaky” IB resulting from GM and their metabolites, we reviewed the selected publications, including the role of the BBB as the immune barrier, systemic chronic inflammation and inflammation influences on BBB permeability, NF&ND, and brain aging. To add depth to the bridging role of systemic chronic inflammation, a plausible mechanism indispensable for BBB corruption was highlighted; namely, BBB maintenance cues are affected by inflammatory cytokines, which may help to understand how GM and its metabolites play a major role in NF&ND and aging.

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“…As alcohol use is closely associate with TBI, alcohol may affect RBC clearance and iron regulation. Similarly, many studies have shown that traumatic brain injury activates microglia, the scavenging cells of the brain [20,21]. As a result, activated microglia may also play a role in iron management.…”

Section: Introductionmentioning

confidence: 97%