DOI: 10.1002/ame2.70151
Source-dependent variability in gut barrier disruption,bacterial translocation,and immune activation after ischemic stroke in Wistar rats
Cristina Granados-Martinez1
Nuria Alfageme-Lopez1
Manuel Navarro-Oviedo1
Victor Mora-Cuadrado2
David Sevillano-Fernandez3
Luis Alou-Cervera3
Maria Encarnación Fernandez-Valle4
Olivia Hurtado5
Maria A.Moro6
Ignacio Lizasoain1
Jesus Miguel Pradillo1
1.Pharmacology and Toxicology Department and University Research Institute of Neurochemistry,School of Medicine,University Complutense of Madrid,Madrid,Spain;Research Institute Hospital Universitario 12 de Octubre of Madrid,Madrid,Spain2.Research Institute Hospital Universitario 12 de Octubre of Madrid,Madrid,Spain3.Microbiology Section,School of Medicine,University Complutense of Madrid,Madrid,Spain4.ICTS Complutense Bioimaging(Biolmac),Research Assistance Centre,Complutense University of Madrid,Madrid,Spain5.Pharmacology and Toxicology Department and University Research Institute of Neurochemistry,School of Medicine,University Complutense of Madrid,Madrid,Spain6.Neurovascular Pathophysiology,Cardiovascular Risk Factor and Brain Health Program,Centro Nacional de Investigaciones Cardiovasculares(CNIC),Madrid,Spain
摘要：Stroke induces profound neuroinflammation and systemic immune dysregulation,including disturbances in gut homeostasis.Experimental evidence suggests that in-testinal barrier permeability(IBP)and bacterial translocation(BT)critically influence stroke outcomes.However,biological variability among commonly used rodent sub-strains has received limited attention.In this pilot study,we compared poststroke immune responses in two Wistar rat substrains obtained from different suppliers:RccHan(Envigo)and RjHan(Janvier).Naive animals(n=4)and rats subjected to perma-nent cerebral ischemia(n=8 per substrain)were evaluated 72 h after middle cerebral artery occlusion and stratified according to the presence or absence of BT.Immune cell populations in blood and bone marrow were analyzed using flow cytometry,and leukocyte infiltration into ischemic brain tissue was quantified using immunohisto-chemistry.Differences were considered statistically significant when p＜0.05.Both substrains developed significant infarcts and neurological deficits.RccHan rats exhib-ited larger infarct volumes and more extensive BT across multiple organs.In contrast,RjHan rats exhibited BT mainly confined to mesenteric lymph nodes but exhibited greater IBP.Although dissemination was broader in RccHan rats,overall bacterial bur-den was slightly lower compared with RjHan,and extraintestinal bacterial composi-tion differed between groups.Particularly,RjHan rats exhibited stronger systemic and central immune activation,with significant alterations in lymphocyte and monocyte populations and enhanced granulocyte and T-cell infiltration within ischemic lesions.These findings demonstrate that substrain origin profoundly influences poststroke intestinal barrier integrity,bacterial dissemination,and immune responses considering substrain-related variability is essential to improve reproducibility and translational relevance in preclinical stroke research.
机标关键词：variabilitywistarbarrierstrokesourceafterratsactivation
论文发表日期：2026-02-28
在线出版日期：2026-03-31（本平台首次上网日期，不代表文献的发表时间）
页数：10( 389-398 )
英文信息