Identification of a neurovascular signaling pathway regulating seizures in mice.

ABSTRACT:

Objective

A growing body of evidence suggests that increased blood-brain barrier (BBB) permeability can contribute to the development of seizures. The protease tissue plasminogen activator (tPA) has been shown to promote BBB permeability and susceptibility to seizures. In this study, we examined the pathway regulated by tPA in seizures.

Methods

An experimental model of kainate-induced seizures was used in genetically modified mice, including mice deficient in tPA (tPA (-/-) ), its inhibitor neuroserpin (Nsp (-/-) ), or both (Nsp:tPA (-/-) ), and in mice conditionally deficient in the platelet-derived growth factor receptor alpha (PDGFRα).

Results

Compared to wild-type (WT) mice, Nsp (-/-) mice have significantly reduced latency to seizure onset and generalization; whe

SUBMITTER: Fredriksson L 

PROVIDER: S-EPMC4531055 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature