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PHA-543613 Preserves Blood-Brain Barrier Integrity After Intracerebral Hemorrhage in Mice

PHA-543613 Preserves Blood-Brain Barrier Integrity After Intracerebral Hemorrhage in Mice

Paul R Krafft, Basak Caner, Damon Klebe, William B Rolland, Jiping Tang, John H Zhang

Stroke. 2013 Jun;44(6):1743-7.

PMID: 23613493

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP478149530	PHA-543613		478149-53-0	Price

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