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Updated: Jul 4, 2026
Quantification of Neurovascular Protection Following Repetitive Hypoxic Preconditioning and Transient Middle Cerebral Artery Occlusion in Mice
Published on: May 4, 2015
BMP7 reduces synergistic injury induced by methamphetamine and ischemia in mouse brain
Hui Shen1, Yu Luo, Chi-Chung Kuo
1National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD 21224, United States.
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.
Insights
Methamphetamine (MA) worsens ischemic brain injury by suppressing bone morphogenetic protein 7 (BMP7). BMP7 treatment reduced this synergistic neurodegeneration, suggesting a protective role against combined MA and stroke damage.
Area of Science:
- Neuroscience
- Pharmacology
- Pathology
Background:
- Methamphetamine (MA) exacerbates ischemic brain injury.
- Bone morphogenetic protein 7 (BMP7) demonstrates protective effects against MA-induced and ischemic brain damage individually.
Purpose of the Study:
- To investigate the neuroprotective potential of BMP7 against the combined injury of MA and cerebral ischemia.
- To determine if BMP7 can mitigate the synergistic neurotoxic effects of MA and ischemia.
Main Methods:
- Adult CD-1 mice received MA or saline, followed by middle cerebral artery occlusion (MCAO) for 90 minutes.
- Quantitative real-time polymerase chain reaction (qRT-PCR) assessed BMP7 mRNA expression.
- Caspase-3/7 activity assays and triphenyl-tetrazolium chloride (TTC) staining evaluated cell death and infarction.
Main Results:
- MA treatment suppressed BMP7 mRNA expression in the cerebral cortex.
- Pretreatment with MA significantly enhanced cerebral infarction and caspase-3/7 activity post-ischemia.
- BMP7 administration attenuated the increased infarction and caspase-3/7 activity caused by MA and ischemia.
Conclusions:
- MA potentates ischemic brain injury, potentially by downregulating BMP7 expression.
- BMP7 exhibits a protective effect against the synergistic neurotoxicity of combined MA exposure and cerebral ischemia.
- Targeting BMP7 may offer a therapeutic strategy for individuals with co-occurring MA abuse and stroke.
