Should losartan be administered following brain injury?

Alon Friedman, Guy Bar-Klein, Yonatan Serlin, Yisrael Parmet, Uwe Heinemann, Daniela Kaufer

Research output: Contribution to journalReview articlepeer-review

36 Scopus citations

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.

Original languageEnglish
Pages (from-to)1365-1375
Number of pages11
JournalExpert Review of Neurotherapeutics
Volume14
Issue number12
DOIs
StatePublished - 1 Dec 2014

Keywords

  • blood-brain barrier
  • brain injury
  • epileptogenesis
  • losartan
  • post-injury epilepsy
  • transforming growth factor β

ASJC Scopus subject areas

  • Neuroscience (all)
  • Clinical Neurology
  • Pharmacology (medical)

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