Loss of Endothelial Dysregulates Neural Function In Vivo.

Background: We recently found that loss of endothelial cell disrupts neurovascular and synaptic function. However, whether endothelial is detrimental or protective for neural function under physiological conditions is unknown. Therefore, the goal of this study was to determine the role of endothelial cell in regulating brain function in vivo.

Methods And Results: We developed /Cdh5(PAC)-CreERT2 and /Cdh5(PAC)-CreERT2 (control) mice. Knockdown of endothelial cell was induced at ≈4 to 5 weeks of age. Experiments were conducted at 9 months of age to evaluate neurovascular and neuronal function via biochemistry, immunohistochemistry, behavior tests, and electrophysiology. Endothelial cell knockdown resulted in higher neurovascular permeability, lower claudin-5 vessel coverage, impaired trace fear memory extinction, and disruption of cortical excitatory-inhibitory balance of synaptic activity.

Conclusions: Our data support the novel concept that endothelial cell is protective for brain function when other cell types express .