Insular hemorrhagic stroke in mice: a model of neurocardiac dysfunction

Ventris-Godoy, A. C.; Abramo, H.; Rodrigues-Ribeiro, L.; Rocha Viana, A. C.; Pires, G.; Santos, R. A. S.; Rocha-Resende, C.; Peliky Fontes, M. A.

doi:10.64898/2026.08.03.741256

bioRxiv · 10.64898/2026.08.03.741256

Insular hemorrhagic stroke in mice: a model of neurocardiac dysfunction

Ventris-Godoy, A. C.·Abramo, H.·Rodrigues-Ribeiro, L.·Rocha Viana, A. C.·Pires, G.·Santos, R. A. S.·Rocha-Resende, C.·Peliky Fontes, M. A.

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Abstract

BackgroundInsular damage leads to marked cardiovascular alterations and the mechanisms need to be understood. Mouse models provide unique opportunities to gain insights into pathophysiological mechanisms. Here, we evaluated the effects of rilmenidine, a centrally acting antihypertensive drug, on the cardiac functional parameters and cardiac inflammatory cell infiltration in a newly developed mice model of insular hemorrhagic stroke. MethodsC57BL/6J mice were instrumented for injection of blood or vehicle into the insular cortex (IC). Immediately after IC stroke induction, separate groups received intraperitoneal treatment with vehicle (0.9% NaCl, 0.1 mL/100 g) or rilmenidine (10 g/kg) for three days. Electrocardiogram recording,cardiac catecholamine levels and myocardial accumulation of immune cells were evaluated. ResultsMice subjected to hemorrhagic stroke exhibited higher baseline heart rate (HR) (control: 296 {+/-} 33 bpm vs. stroke: 349 {+/-} 38 bpm; P < 0.01) and prolonged QTc interval (control: 89 {+/-} 11 ms vs. stroke: 100 {+/-} 7 ms; P < 0.01). Stroke also increased cardiac norepinephrine levels (control: 9 {+/-} 4 ng/mg vs. stroke: 25 {+/-} 14 ng/mg; P < 0.05), as well as the number of myocardial CD68+ macrophages (control: 7 {+/-} 4 vs. stroke: 16 {+/-} 6 cells/field; P < 0.0001) and Ly6G+ neutrophils (control: 0.5 {+/-} 0.7 vs. stroke: 1.5 {+/-} 1 cells/field; P < 0.001). Rilmenidine treatment markedly prevented all major stroke- induced myocardial functional and inflammatory changes ConclusionsInsular hemorrhagic stroke in mice induces centrally mediated cardiac noradrenergic hyperactivation accompanied by myocardial accumulation of immune cells. These findings support the relevance of this murine model for investigating mechanisms associated with insular stroke.

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Ventris-Godoy, A. C., Abramo, H., Rodrigues-Ribeiro, L., Rocha Viana, A. C., Pires, G., Santos, R. A. S., Rocha-Resende, C., Peliky Fontes, M. A.. 2026-08-07. Insular hemorrhagic stroke in mice: a model of neurocardiac dysfunction. https://doi.org/10.64898/2026.08.03.741256

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