2-(-2-benzofuranyl)-2-imidazoline induces Bcl-2 expression and provides neuroprotection against transient cerebral ischemia in rats

Download
  1. Get@NRC: 2-(-2-benzofuranyl)-2-imidazoline induces Bcl-2 expression and provides neuroprotection against transient cerebral ischemia in rats (Opens in a new window)
DOIResolve DOI: http://doi.org/10.1016/j.brainres.2010.09.029
AuthorSearch for: ; Search for: ; Search for: ; Search for: ; Search for:
TypeArticle
Journal titleBrain Research
Volume1361
Pages8692; # of pages: 7
Subject2-BFI; Bcl-2; Cell death; Rat; Cerebral ischemia; Stroke; Brain
AbstractStroke is the third leading cause of death and disability in North America and is becoming the most frequent cause of death in the rapid developing China. Protecting neurons in order to minimize brain damagerepresents aneffective approach towards stroke therapeutics. Our recent study demonstrated that 2-(-2-benzofuranyl)-2-imidazoline (2-BFI), a ligand for imidazoline I2 receptors, is potently neuroprotective against stroke, possibly through transiently antagonizing NMDA receptor activities. In this study, we further investigated the characteristics and mechanisms of 2-BFI-mediated neuroprotection using a rat stroke model of transient occlusion of themiddlecerebral artery.Here,weshowthat2-BFIwasmosteffectiveat thedoseof 3mg/kgin vivo,with significantly reduced brain infarct size and improved neurological deficits. Lower doses of 2-BFI at 1.5mg/kg, or higher dose of 2-BFI at 6 mg/kg, were either not effective, or toxic to the brain, respectively. Treating stroke rats with 3 mg/kg 2-BFI significantly reduced the number of TUNEL positive cells and preserved the integrity of subcellular structures such as nuclear membranes and mitochondria as shown under the electron microscope, confirming neuroprotection. Most interestingly, 2-BFI-treated brains exhibited significant expression of Bcl-2, a gene with a known function in neuroprotection. Taken together, these studies not only demonstrated that 2-BFI at 3 mg/kg was effective in neuroprotection, but also, for the first time, showed that 2-BFI provided neuroprotection through up-regulating the neuroprotective gene Bcl- 2. 2-BFI can be further developed as a therapeutic drug for stroke treatment.
Publication date
LanguageEnglish
AffiliationNRC Institute for Biological Sciences; National Research Council Canada
Peer reviewedYes
NPARC number17476265
Export citationExport as RIS
Report a correctionReport a correction
Record identifierc921d383-164a-405e-91e6-b2376182994f
Record created2011-03-30
Record modified2016-05-09
Bookmark and share
  • Share this page with Facebook (Opens in a new window)
  • Share this page with Twitter (Opens in a new window)
  • Share this page with Google+ (Opens in a new window)
  • Share this page with Delicious (Opens in a new window)