Channelpedia

PubMed 24380477


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: TRP , TRPM , TRPM4



Title: Effect of glibenclamide on the prevention of secondary brain injury following ischemic stroke in humans.

Authors: Arjun Khanna, Brian P Walcott, Kristopher T Kahle, J Marc Simard

Journal, date & volume: Neurosurg Focus, 2014 Jan , 36, E11

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24380477


Abstract
Cerebral edema and hemorrhagic conversion are common, potentially devastating complications of ischemic stroke and are associated with high rates of mortality and poor functional outcomes. Recent work exploring the molecular pathophysiology of the neurogliovascular unit in ischemic stroke suggests that deranged cellular ion homeostasis due to altered function and regulation of ion pumps, channels, and secondary active transporters plays an integral role in the development of cytotoxic and vasogenic edema and hemorrhagic conversion. Among these proteins involved in ion homeostasis, the ischemia-induced, nonselective cation conductance formed by the SUR1-TRPM4 protein complex appears to play a prominent role and is potently inhibited by glibenclamide, an FDA-approved drug commonly used in patients with Type 2 diabetes. Several robust preclinical studies have demonstrated the efficacy of glibenclamide blockade of SUR1-TRPM4 activity in reducing edema and hemorrhagic conversion in rodent models of ischemic stroke, prompting the study of the potential protective effects of glibenclamide in humans in an ongoing prospective phase II clinical trial. Preliminary data suggest glibenclamide significantly reduces cerebral edema and lowers the rate of hemorrhagic conversion following ischemic stroke, suggesting the potential use of glibenclamide to improve outcomes in humans.