Molecular Imaging of Inflammation along the Heart-Brain-Axis in Two Mouse Models of Cerebral Stroke

Ziel/Aim Ischemic stroke increases risk of acute cardiac events and chronic heart failure. While thought to involve systemic inflammation, the precise mechanism is poorly characterized. We hypothesized that acute cerebral stroke will induce cardiac inflammation and contractile dysfunction, detectable by positron emission tomography (PET).

Methodik/Methods C57Bl6 mice underwent surgical cerebral stroke by 45 min middle cerebral artery occlusion (MCAo, n = 32) or craniotomy and topical application of endothelin-1 (ET-1, n = 12). Shams were immediate reperfusion (n = 8) or vehicle (n = 4). Serial PET imaging with F-18-GE180 of mitochondrial translocator protein (TSPO) measured brain and heart inflammation at 24 h, 7d and 21d after stroke. Magnetic resonance imaging at 1 wk and 3 wk determined stroke size and left ventricular function.

Ergebnisse/Results F-18-GE180 uptake was lower in stroke region compared to contralateral 24 h after MCAo (%injected dose (ID)/g: 1.6 ± 0.3 vs 1.9 ± 0.2, p = 0.01), reflecting lower perfusion. Signal was higher at 7d (2.2 ± 0.6 vs 1.9 ± 0.3 p = 0.28) and 21d. Sham mice exhibited lower TSPO in ipsilateral side (1.4 ± 0.14, p = 0.23 to MCAo). ET-1 showed higher TSPO PET signal in affected hemisphere from 7d (3.3 ± 0.8 vs 2.0 ± 0.6, p < 0.001) but was similar to sham. After MCAo stroke, cardiac TSPO signal was elevated compared to sham (%ID/g, 1d: 8.6 ± 0.4 vs 6.8 ± 0.4, p = 0.015; 7d: 9.2 ± 0.7, p = 0.013) and declined by 21 days. By contrast, minimal difference in cardiac TSPO PET signal was observed for ET-1. MCAo induced acute contractile dysfunction at 6d (% ejection fraction: 49 ± 4 vs 65 ± 3, p = 0.08), which remained depressed chronically (55 ± 1 vs 62 ± 2 p = 0.01). ET-1-induced stroke did not affect contractile function.

Schlussfolgerungen/Conclusions Stroke evokes modest TSPO upregulation in brain and heart, reflecting systemic inflammation, contributing to cardiac function. MCAo impairs cardiac function more reliably than topical ET-1. These findings provide a foundation for monitoring systemic inflammatory activation and cardiac damage after cerebral injury.