PHA-543613 preserves blood-brain barrier integrity after intracerebral hemorrhage in mice.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 23613493.
- Also identified by DOI 10.1161/STROKEAHA.111.000427 and PMC identifier 3696522.
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Abstract
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. 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. 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. 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.
Medical subject headings
- Blood-Brain Barrier
- Bridged Bicyclo Compounds, Heterocyclic
- Cerebral Hemorrhage
- Quinuclidines
- Receptors, Nicotinic
- Signal Transduction