Abstract
BACKGROUND AND PURPOSE: Blood-brain barrier disruption and consequent vasogenic edema formation codetermine the clinical course of intracerebral hemorrhage (ICH). This study examined the effect of PHA-543613, a novel α7 nicotinic acetylcholine receptor agonist, on blood-brain barrier preservation after ICH.
METHODS: Male CD-1 mice, subjected to intrastriatal blood infusion, received PHA-543613 alone or in combination with α7 nicotinic acetylcholine receptor antagonist methyllycaconitine or phosphatidylinositol 3-kinase inhibitor wortmannin.
RESULTS: PHA-543613 alone, but not in combination with methyllycaconitine or wortmannin, inhibited glycogen synthase kinase-3β, thus, stabilizing β-catenin and tight junction proteins, which was paralleled by improved blood-brain barrier stability and ameliorated neurofunctional deficits in ICH animals.
CONCLUSIONS: PHA-543613 preserved blood-brain barrier integrity after ICH, possibly through phosphatidylinositol 3-kinase-Akt-induced inhibition of glycogen synthase kinase-3β and β-catenin stabilization.
Original language | English |
---|---|
Pages (from-to) | 1743-1747 |
Number of pages | 5 |
Journal | Stroke |
Volume | 44 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2013 |
ASJC Scopus Subject Areas
- Clinical Neurology
- Cardiology and Cardiovascular Medicine
- Advanced and Specialized Nursing
Keywords
- Blood-brain barrier
- Intracerebral hemorrhage
- Mice
- PHA-543613
- α7 nicotinic acetylcholine receptor
- Claudin-3/metabolism
- Receptors, Nicotinic/physiology
- Phosphatidylinositol 3-Kinases/metabolism
- Glycogen Synthase Kinase 3 beta
- Male
- Proto-Oncogene Proteins c-akt/metabolism
- Glycogen Synthase Kinase 3/antagonists & inhibitors
- Mice, Inbred Strains
- Signal Transduction/drug effects
- Aconitine/analogs & derivatives
- Bridged Bicyclo Compounds, Heterocyclic/pharmacology
- Animals
- Blood-Brain Barrier/drug effects
- beta Catenin/metabolism
- Wortmannin
- Cerebral Hemorrhage/metabolism
- Androstadienes/pharmacology
- Quinuclidines/pharmacology
- Disease Models, Animal