Endothelial Cell Regulates Neurovascular, Neuronal, and Behavioral Function.

Background: Specialized brain endothelial cells and human are independently important for neurovascular function, yet whether expression by endothelial cells contributes to brain function is currently unknown. In the present study, we determined whether the loss of endothelial cell impacts brain vascular and neural function.

Methods: We developed /Cdh5(PAC)-CreERT2 () and /Cdh5(PAC)-CreERT2 (, control) mice and induced endothelial cell knockdown with tamoxifen at ≈4 to 5 weeks of age. Neurovascular and neuronal function were evaluated by biochemistry, immunohistochemistry, behavioral testing, and electrophysiology at 9 months of age.

Results: We found that the loss of endothelial expression was sufficient to cause neurovascular dysfunction including higher permeability and lower vessel coverage in tandem with deficits in spatial memory and fear memory extinction and a disruption of cortical excitatory/inhibitory balance.

Conclusions: Our data collectively support the novel concept that endothelial plays a critical role in the regulation of the neurovasculature, neural circuit function, and behavior.