INFLUENCE OF NATURAL MICROBIOTA ON IMMUNE INFILTRATION AND MOTOR RECOVERY AFTER STROKE IN THE WILDLING MOUSE MODEL

Ischaemic stroke is major cause of death and disability, which results from a blocked cerebral vessel. Immune cell infiltration after stroke can worsen insular cortex injury, disrupting autonomic control of the heart, which contributes to stroke-heart syndrome. Most stroke-heart syndrome studies use animals kept in sterile conditions with homogeneous microbiota and immature immunity, limiting translation to humans with a mature, microbially shaped immune system.
A new strain of mice termed “wildlings” was generated by transferring embryos from specific pathogen-free (SPF) mice to wild-caught mice, resulting in offspring with a developed immune system that more closely resembles human immunological features. To induce ischaemic stroke, Wildling and SPF mice underwent middle cerebral artery occlusion (MCAo) surgery. Spectral flow cytometry was used to examine immune cell infiltration in the brain, heart, and blood. Cytokines in the blood after stroke were measured using the proximity extension assay. Ladder rung behavioral test was included to assess fine motor skills after stroke.
Spectral flow cytometry analysis revealed sex differences in immune infiltration in the organs after the stroke. Elevated macrophages and monocytes in the heart were detected as a hallmark of stroke-heart syndrome. We were also able to detect differences in motor skills recovery between SPF and Wildling mice using ladder rung test analysis.
Our study showed differences in immune cell infiltration in the brain, heart, and blood after ischaemic stroke between SPF and Wildling mice. Nevertheless, future studies will include a deeper characterisation of the model that allows testing therapeutic strategies.