Hepatic fibrosis is associated with more severe acute ischemic stroke

Chatzopoulos, Georgios S.; Filippidis, Athanasios; Gogou, Christiana; Erythropoulou-Kaltsidou, Anastasia; Kiosi, M.; Kontana, Anastasia; Kostourou, Danai-Thomais; Kourtidou, Christodoula; Kyziroglou, Maria; Mentizis, P.; Milonas, Dimitrios; Savopoulos, Christos; Τζιόμαλος, Κωνσταντίνος

doi:10.1016/j.atherosclerosis.2021.06.124

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“…Non-alcoholic steatohepatitis (NASH) is a form of NAFLD in which steatosis in the liver is accompanied by inflammation and cell damage. NAFLD is a chronic liver disease that is present in 50–60% of patients with T2DM, and the two conditions often act synergistically to aggravate the severity of outcomes from ischemic stroke ( Megherbi et al, 2003 ; Putaala et al, 2011 ; Seo et al, 2016 ; Li et al, 2018 ; Weinstein A. et al, 2018 ; Chatzopoulos et al, 2021 ). Given the global prevalence of NAFLD, and the increased post-stroke morbidity and mortality in the expanding diabetic population, there is a compelling need to elucidate the brain-liver interaction after stroke in the setting of T2DM and to develop therapeutic approaches specifically designed, not only to reduce stroke induced direct neurological and cognitive deficits, but also to reduce liver damage driven by the interaction of brain and liver.…”

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confidence: 99%

Therapeutic effects of CD133 + Exosomes on liver function after stroke in type 2 diabetic mice

et al. 2023

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Background and purposeNon-alcoholic fatty liver disease (NAFLD) is known to adversely affect stroke recovery. However, few studies investigate how stroke elicits liver dysfunction, particularly, how stroke in type 2 diabetes mellitus (T2DM) exacerbates progression of NAFLD. In this study, we test whether exosomes harvested from human umbilical cord blood (HUCBC) derived CD133 + cells (CD133 + Exo) improves neuro-cognitive outcome as well as reduces liver dysfunction in T2DM female mice.MethodsFemale, adult non-DM and T2DM mice subjected to stroke presence or absence were considered. T2DM-stroke mice were randomly assigned to receive PBS or Exosome treatment group. CD133 + Exo (20 μg/200 μl PBS, i.v.) was administered once at 3 days after stroke. Evaluation of neurological (mNSS, adhesive removal test) and cognitive function [novel object recognition (NOR) test, odor test] was performed. Mice were sacrificed at 28 days after stroke and brain, liver, and serum were harvested.ResultsStroke induces severe and significant short-term and long-term neurological and cognitive deficits which were worse in T2DM mice compared to non-DM mice. CD133 + Exo treatment of T2DM-stroke mice significantly improved neurological function and cognitive outcome indicated by improved discrimination index in the NOR and odor tests compared to control T2DM-stroke mice. CD133 + Exo treatment of T2DM stroke significantly increased vascular and white matter/axon remodeling in the ischemic brain compared to T2DM-stroke mice. However, there were no differences in the lesion volume between non-DM stroke, T2DM-stroke and CD133 + Exo treated T2DM-stroke mice. In T2DM mice, stroke induced earlier and higher TLR4, NLRP3, and cytokine expression (SAA, IL1β, IL6, TNFα) in the liver compared to heart and kidney, as measured by Western blot. T2DM-stroke mice exhibited worse NAFLD progression with increased liver steatosis, hepatocellular ballooning, fibrosis, serum ALT activity, and higher NAFLD Activity Score compared to T2DM mice and non-DM-stroke mice, while CD133 + Exo treatment significantly attenuated the progression of NAFLD in T2DM stroke mice.ConclusionTreatment of female T2DM-stroke mice with CD133 + Exo significantly reduces the progression of NAFLD/NASH and improves neurological and cognitive function compared to control T2DM-stroke mice.

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