title: BMP7 reduces synergistic injury induced by methamphetamine and ischemia in mouse brain.
abstract: Previous studies have indicated that methamphetamine (MA) potentiates neurodegeneration induced by ischemia in brain. We, and others, have reported that bone morphogenetic protein 7 (BMP7) is protective against MA and ischemic brain injury. The purpose of this study is to examine whether BMP7 reduces synergistic injury induced by both MA and cerebral ischemia. Adult CD-1 mice were treated with MA (4x 10mg/kg, each dose 2h apart) or saline. Using the quantitative real time polymerase chain reaction, we found that MA suppressed the expression of BMP7 mRNA in the cerebral cortex 1 day after injection. Ischemic and reperfusional injuries were introduced by ligation of the right middle cerebral artery for 90min after MA injection. Animals were sacrificed for caspase-3/7 activity assay and tri-phenyl-tetrazolium chloride staining at 1h and 2 days after reperfusion, respectively. Cerebral infarction and caspase-3/7 activity were enhanced in the stroke animals pretreated with MA; both responses were attenuated by pretreatment with BMP7. In conclusion, our data suggest that MA facilitates cerebral infarction after ischemia possibly mediated, in part, through the suppression of BMP7.
authors.affiliation: National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD 21224, United States.
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: Yu
authors.initials: Y
authors.lastname: Luo
authors.forename: Chi-Chung
authors.initials: CC
authors.lastname: Kuo
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage / Q000378:metabolism*; D002545:Brain Ischemia / Q000473:pathology*; D053148:Caspase 3 / Q000187:drug effects; D053179:Caspase 7 / Q000187:drug effects; D015259:Dopamine Agents / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D015259:Dopamine Agents; D016212:Transforming Growth Factor beta; D008694:Methamphetamine; D053148:Caspase 3; D053179:Caspase 7