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Updated: Jan 10, 2026
Isolation and Flow Cytometric Assessment of Neuroimmune Interactions in a Mini-Stroke Murine Model
Published on: June 20, 2025
Cerebral ischaemic stroke results in altered mucosal antibody responses and host-commensal microbiota interactions
Madeleine Hurry1, David A Posner2, Raymond Wong1
1School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, M13 9PL, the United Kingdom of Great Britain and Northern Ireland; Lydia Becker Institute of Immunology and Inflammation, University of Manchester, the United Kingdom of Great Britain and Northern Ireland; Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust, University of Manchester, Manchester, the United Kingdom of Great Britain and Northern Ireland.
Abstract:
Stroke is a devastating neurological event with a high risk of mortality that results in long-term sequalae that extend beyond the central nervous system. Notably these include gastrointestinal dysfunction and altered composition of the commensal microbiota in both patients and mouse models, which have been suggested to contribute to secondary infection and poor clinical outcomes following stroke. Strikingly, changes in commensal microbial community composition occur rapidly following stroke and correlate with disease severity. Despite these observations, the underpinning mechanisms that drive perturbation of the microbiota post-stroke remain poorly understood. The gastrointestinal tract is home to a complex network of tissue-resident immune cells that maintain homeostatic interactions with commensal microbes and prevent bacterial-driven inflammation. Here we demonstrate mice subjected to ischaemic stroke exhibit alterations in the intestinal immune system, most notably in class switched germinal centre B cells and the production of Immunoglobulin A (IgA) - a major effector response against commensal microbes. Mice lacking secretory antibodies, including IgA, exhibited a partial reversion of stroke-induced changes in microbiota composition. Together these findings demonstrate stroke is associated with dysregulation of antibody producing immune responses, which may in part explain changes in the intestinal microbiota. A mechanistic understanding of the immunological basis of stroke-associated pathologies in the periphery may open new avenues to manage the secondary complications and long-term prognosis of patients suffering from neurological disease.
Insights
Stroke rapidly alters gut microbiota composition. This study reveals stroke disrupts the immune system, specifically immunoglobulin A (IgA) production, which may explain these microbial changes and inform new treatment strategies.
Area of Science:
- Neuroimmunology
- Gastroenterology
- Microbiome Research
Background:
- Stroke causes significant mortality and long-term neurological deficits.
- Post-stroke gastrointestinal dysfunction and altered gut microbiota are linked to poor outcomes and secondary infections.
- Mechanisms driving gut microbiota changes after stroke are poorly understood.
Purpose of the Study:
- To investigate the impact of ischemic stroke on the intestinal immune system.
- To determine the role of specific immune responses, like Immunoglobulin A (IgA), in stroke-induced microbiota alterations.
- To explore potential therapeutic targets for managing secondary complications of stroke.
Main Methods:
- Induction of ischemic stroke in mouse models.
- Analysis of intestinal immune cell populations, focusing on class-switched germinal center B cells.
- Quantification of Immunoglobulin A (IgA) production.
- Assessment of gut microbiota composition in wild-type and IgA-deficient mice post-stroke.
Main Results:
- Ischemic stroke induced significant alterations in the intestinal immune system of mice.
- Key changes were observed in class-switched germinal center B cells and IgA production.
- Mice lacking secretory antibodies, including IgA, showed a partial reversal of stroke-associated microbiota changes.
- Stroke is linked to dysregulated antibody-producing immune responses affecting the gut microbiota.
Conclusions:
- Stroke significantly impacts the gut immune system, particularly antibody responses.
- Dysregulation of IgA production may be a key mechanism driving post-stroke gut dysbiosis.
- Understanding these neuro-immune-microbiota interactions offers potential for novel therapeutic strategies to improve stroke patient outcomes.
