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Endothelial TLR4 and the microbiome drive cerebral cavernous malformations
Blood Vessel Immune Sensor and Gut Bacteria May Influence Brain Blood Vessel Malformations
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Abstract
Endothelial Toll-like receptor 4 (TLR4) and the gut microbiome are critical stimulants of cerebral cavernous malformation (CCM) formation.
- Activation of TLR4 by Gram-negative bacteria or lipopolysaccharide may accelerate CCM formation.
- Genetic or pharmacologic blockade of TLR4 signalling is associated with prevention of CCM formation in mice.
- Polymorphisms that increase expression of the TLR4 gene or its co-receptor CD14 are associated with higher CCM lesion burden in humans.
- Germ-free mice show protection against CCM formation.
- A single course of antibiotics can permanently alter CCM susceptibility in mice.
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