title: Should losartan be administered following brain injury?
abstract: Brain injury is a major health concern and associated with delayed neurological complications, including post-injury epilepsy, cognitive and emotional disabilities. Currently, there is no strategy to prevent post-injury delayed complications. We recently showed that dysfunction of the blood-brain barrier, often reported in brain injuries, can lead to epilepsy and neurodegeneration via activation of inflammatory TGF-β signaling in astrocytes. We further showed that the FDA approved angiotensin II type 1 receptor antagonist, losartan, blocks brain TGF-β signaling and prevents epilepsy in the albumin or blood-brain barrier breakdown models of epileptogenesis. Here we discuss the potential of losartan as an anti-epileptogenic and a neuroprotective drug, the rationale of its use following brain injury and the challenges of designing clinical trials. We highlight the urgent need to develop reliable biomarkers for epileptogenesis (and other complications) after brain injury as a pre-requisite to challenge neuroprotective therapies.
authors.affiliation: Department of Medical Neuroscience, Faculty of Medicine, Dalhousie University, PO Box 15000, 5850 College Street, Halifax Nova Scotia B3H 4R2, Canada.
authors.forename: Alon
authors.initials: A
authors.lastname: Friedman
authors.forename: Guy
authors.initials: G
authors.lastname: Bar-Klein
authors.forename: Yonatan
authors.initials: Y
authors.lastname: Serlin
authors.forename: Yisrael
authors.initials: Y
authors.lastname: Parmet
authors.forename: Uwe
authors.initials: U
authors.lastname: Heinemann
authors.forename: Daniela
authors.initials: D
authors.lastname: Kaufer
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D019808:Losartan / Q000008:administration & dosage / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000378:metabolism
chemical_list: D016212:Transforming Growth Factor beta; D019808:Losartan
keywords: blood–brain barrier; brain injury; epileptogenesis; losartan; post-injury epilepsy; transforming growth factor β