title: Pyruvate blocks blood-brain barrier disruption, lymphocyte infiltration and immune response in excitotoxic brain injury.
abstract: The effects of pyruvate, the end metabolite of glycolysis, on blood-brain barrier (BBB) impairment and immune reactivity were examined in the quinolinic acid (QA)-injected rat striatum. Extensive disruption of BBB was observed at 7 d post QA-injection as demonstrated by increased immunohistochemical staining using antibody against immunoglobulin G (IgG). Animals receiving pyruvate administration (500 mg/kg) with QA-injection exhibited reduced lgG immunoreactivity (by 45%) relative to QA alone. QA intrastriatal injection also resulted in marked increases in the number of infiltrating T-lymphocytes (by 70-fold) and expression of major histocompatibility complex (MHC-class II) (by 45-fold) relative to unlesioned control. Treatment with pyruvate significantly reduced infiltration of T-cells (by 68%) and MHC class II expression (by 48%) induced by QA. These results indicate that QA injection into rat striatum leads to impairment in BBB function with pyruvate administration reducing immune response and BBB leakiness in excitotoxic injury.
authors.affiliation: Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia Vancouver, BC, V6T 1Z3, Canada.
authors.forename: Jae K
authors.initials: JK
authors.lastname: Ryu
authors.affiliation: Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia Vancouver, BC, V6T 1Z3, Canada.
authors.forename: James G
authors.initials: JG
authors.lastname: McLarnon
keywords: Blood-brain barrier (BBB); T-cell infiltration; excitotoxicity; inflammation; pyruvate; rat striatum