Should losartan be administered following brain injury?

Expert Rev Neurother. 2014 Dec;14(12):1365-75. doi: 10.1586/14737175.2014.972945. Epub 2014 Oct 27.


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.

Keywords: blood–brain barrier; brain injury; epileptogenesis; losartan; post-injury epilepsy; transforming growth factor β.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects*
  • Brain / drug effects*
  • Brain / physiopathology
  • Brain Injuries / drug therapy*
  • Brain Injuries / physiopathology
  • Humans
  • Losartan / administration & dosage
  • Losartan / therapeutic use*
  • Signal Transduction / drug effects*
  • Transforming Growth Factor beta / drug effects
  • Transforming Growth Factor beta / metabolism


  • Transforming Growth Factor beta
  • Losartan