Spermine attenuates the preconditioning of diazoxide against transient focal cerebral ischemia in rats.

Abstract

It is known that mitochondrial ATP-sensitive potassium channels (mitoKATP) play a significant role in protecting cerebral function from ischemia-reperfusion injury, which is related with a decrease in the mitochondrial matrix calcium. However, the effect of mitochondrial calcium uniporter (MCU) on diazoxide-induced cerebral protection is still indistinct. The purpose of the present paper is to further observe the relationship between mitoKATP and MCU, and to probe the mechanism. Adult male Wistar rats were randomly divided into five groups: the Sham group, the I-R group, the Dzx+I-R group, the Dzx+Sper+I-R group, and the Sper+I-R group. Rats not in the Sham group were exposed to 2-hour ischemia followed by 24-hour reperfusion. Diazoxide and spermine were administrated 30 minutes before ischemia or 10 minutes before reperfusion, respectively. After 24-hour reperfusion, animals were given neurological performance tests, overdosed with general anesthesia, and then their brains were excised for infarct volume, pathological changes, and apoptosis analysis. The beneficial effects of diazoxide (improved neurological deficits, decreased infarct volume, and apoptosis, evidenced by the decreased expression of cytochrome c and Bax) were significantly neutralized by spermine. The results of the present work suggest that diazoxide-induced cerebral protection against ischemia-reperfusion injury is mediated by spermine through apoptotic pathway.

• Authors: Lin Zhang, Shilei Wang, Huanli Dong, Yu Li, Peng Wang, Shuhong Li, Yunliang Guo, Ruyong Yao
• Journal: Neurological research (Neurol Res) Vol. 36 Issue 7 Pg. 666-72 (Jul 2014) ISSN: 1743-1328 [Electronic] England
• PMID: 24620960 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bax protein, rat
• Calcium Channels
• Neuroprotective Agents
• Potassium Channels
• bcl-2-Associated X Protein
• mitochondrial K(ATP) channel
• mitochondrial calcium uniporter
• Spermine
• Cytochromes c
• Diazoxide

Topics

• Animals
• Apoptosis (drug effects, physiology)
• Brain (drug effects, pathology, physiopathology)
• Calcium Channels (metabolism)
• Cytochromes c (metabolism)
• Diazoxide (pharmacology)
• Infarction, Middle Cerebral Artery (drug therapy, pathology, physiopathology)
• Male
• Neurons (drug effects, pathology, physiology)
• Neuroprotective Agents (pharmacology)
• Potassium Channels (metabolism)
• Random Allocation
• Rats, Wistar
• Reperfusion Injury (pathology, physiopathology, prevention & control)
• Severity of Illness Index
• Spermine (metabolism)
• bcl-2-Associated X Protein (metabolism)