BMP7 reduces synergistic injury induced by methamphetamine and ischemia in mouse brain.
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.
Shen
Hui
H
National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD 21224, United States.
Luo
Yu
Y
Kuo
Chi-Chung
CC
Wang
Yun
Y
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*
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