Molecular imaging of the brain-heart axis provides insights into cardiac dysfunction after cerebral ischemia.
Nele HermannsViola WroblewskiPablo BascuñanaBettina WolfAndras PolyakTobias L RossFrank M BengelJames T ThackerayPublished in: Basic research in cardiology (2022)
Ischemic stroke imparts elevated risk of heart failure though the underlying mechanisms remain poorly described. We aimed to characterize the influence of cerebral ischemic injury on cardiac function using multimodality molecular imaging to investigate brain and cardiac morphology and tissue inflammation in two mouse models of variable stroke severity. Transient middle cerebral artery occlusion (MCAo) generated extensive stroke damage (56.31 ± 40.39 mm 3 ). Positron emission tomography imaging of inflammation targeting the mitochondrial translocator protein (TSPO) revealed localized neuroinflammation at 7 days after stroke compared to sham (3.8 ± 0.8 vs 2.6 ± 0.7 %ID/g max, p < 0.001). By contrast, parenchyma topical application of vasoconstrictor endothelin-1 did not generate significant stroke damage or neuroinflammatory cell activity. MCAo evoked a modest reduction in left ventricle ejection fraction at both 1 weeks and 3 weeks after stroke (LVEF at 3 weeks: 54.3 ± 5.7 vs 66.1 ± 3.5%, p < 0.001). This contractile impairment was paralleled by elevated cardiac TSPO PET signal compared to sham (8.6 ± 2.4 vs 5.8 ± 0.7%ID/g, p = 0.022), but was independent of leukocyte infiltration defined by flow cytometry. Stroke size correlated with severity of cardiac dysfunction (r = 0.590, p = 0.008). Statistical parametric mapping identified a direct association between neuroinflammation at 7 days in a cluster of voxels including the insular cortex and reduced ejection fraction (ρ = - 0.396, p = 0.027). Suppression of microglia led to lower TSPO signal at 7 days which correlated with spared late cardiac function after MCAo (r = - 0.759, p = 0.029). Regional neuroinflammation early after cerebral ischemia influences subsequent cardiac dysfunction. Total body TSPO PET enables monitoring of neuroinflammation, providing insights into brain-heart inter-organ communication and may guide therapeutic intervention to spare cardiac function post-stroke.
Keyphrases
- cerebral ischemia
- subarachnoid hemorrhage
- blood brain barrier
- oxidative stress
- brain injury
- positron emission tomography
- left ventricular
- pet imaging
- heart failure
- computed tomography
- atrial fibrillation
- ejection fraction
- middle cerebral artery
- flow cytometry
- pet ct
- randomized controlled trial
- high resolution
- magnetic resonance
- stem cells
- mouse model
- skeletal muscle
- multiple sclerosis
- aortic stenosis
- ischemia reperfusion injury
- spinal cord injury
- neuropathic pain
- cell therapy
- lipopolysaccharide induced
- protein protein
- bone marrow
- white matter
- spinal cord
- preterm birth
- cognitive impairment
- drug delivery
- double blind
- amino acid