Huperzine A attenuates mitochondrial dysfunction after middle cerebral artery occlusion in rats.

Abstract

Mitochondrial dysfunction has been proved to contribute to ischemia-induced brain damage. In this study, which used a rat middle cerebral artery occlusion (MCAO) model, the protective effects of huperzine A (HupA) against mitochondrial dysfunction and brain damage were investigated. MCAO for 45 min followed by 4 hr of reperfusion significantly impaired the activities of mitochondrial respiratory chain enzymes (complex I, complex II-III, and complex IV) and alpha-ketoglutarate dehydrogenase, increased the production of reactive oxygen species (ROS), and induced mitochondrial swelling. Pretreatment of HupA at 0.1 mg/kg significantly preserved respiratory chain enzyme activities, decreased ROS production, and attenuated mitochondrial swelling. It could also significantly attenuate the neurological deficits (after 4 or 24 hr reperfusion) and reduce infarct volumes (after 24 hr reperfusion). Moreover, HupA protected isolated nonsynaptosomal mitochondria from calcium-induced damage in vitro by preserving mitochondrial membrane potential and decreasing ROS production. Overall, the present study indicates that HupA can ameliorate MCAO-induced mitochondrial dysfunction, and this might partially contribute to its protective effect on brain damage after 24 hr of reperfusion.

• Authors: Chun Yan Zheng, Hai Yan Zhang, Xi Can Tang
• Journal: Journal of neuroscience research (J Neurosci Res) Vol. 86 Issue 11 Pg. 2432-40 (Aug 15 2008) ISSN: 1097-4547 [Electronic] United States
• PMID: 18438924 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkaloids
• Mitochondrial Membrane Transport Proteins
• Neuroprotective Agents
• Reactive Oxygen Species
• Sesquiterpenes
• huperzine A

Topics

• Alkaloids
• Animals
• Brain (drug effects, pathology)
• Infarction, Middle Cerebral Artery (drug therapy, pathology)
• Male
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (drug effects, pathology)
• Mitochondrial Membrane Transport Proteins (drug effects)
• Neuroprotective Agents (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Sesquiterpenes (pharmacology)