title: Mitochondrial calcium uniporter opener spermine attenuates the cerebral protection of diazoxide through apoptosis in rats.
abstract: BACKGROUND
  It is reported that ischemic penumbra is a dynamic process, in which irreversible necrosis in the center of ischemia propagates to the neighboring tissue over time. Recent research has indicated that mitochondrial adenosine triphosphate (ATP)-sensitive potassium channels (mitoKATP) opener diazoxide plays an important role in cerebral protection; however, the role of mitochondrial calcium uniporter (MCU) in the effect of diazoxide on penumbra and infarct core remains unclear.
  
  
  METHODS
  Adult male Wistar rats were randomly divided into 5 groups: the Sham group, the ischemia-reperfusion (I/R) group, the diazoxide and ischemia-reperfusion (Dzx + I/R) group, the diazoxide and spermine and ischemia-reperfusion (Dzx + Sper + I/R) group, and the spermine and ischemia-reperfusion (Sper + I/R) group. The animals were exposed to 24-hour reperfusion after 2-hour ischemia. Diazoxide and spermine were administrated at 30 minutes or 10 minutes before the beginning of ischemia or reperfusion, respectively. After 24-hour reperfusion, animals were given neurologic performance tests and when overdosed with general anesthesia their brains were excised for infarct volume, apoptosis, and immunohistochemical.
  
  
  RESULTS
  Rats in the Dzx + I/R group displayed improved neurologic deficits, decreased infarct volume in cortex but not in subcortex, and apoptosis (evidenced by decreased terminal deoxynucleotidyl transferase-mediated dUTP nick end lebeling-positive percentage and the immunohistochemistry of cytochrome c) in cortex caused by ischemia/reperfusion. Rats in the Dzx + Sper + I/R group displayed worse neurologic deficits, larger infarct volume in cortex but not in subcortex, and more apoptosis both in penumbra and infarct core of cortex than those in the Dzx + I/R group.
  
  
  CONCLUSIONS
  Results in our study suggested that diazoxide improved neurologic deficits, decreased infarct volume in cortex but not in subcortex, and apoptosis in cortex against ischemia/reperfusion injury is mediated by spermine.
authors: Department of Anesthesiology, Liaocheng People's Hospital, Liaocheng, Shandong, China.
authors: Lei
authors: L
authors: Zhang
authors: Department of Anesthesiology, Liaocheng People's Hospital, Liaocheng, Shandong, China.
authors: Xiujuan
authors: X
authors: Gao
authors: Department of Anesthesiology, Liaocheng People's Hospital, Liaocheng, Shandong, China.
authors: Xin
authors: X
authors: Yuan
authors: Department of Anesthesiology, Liaocheng People's Hospital, Liaocheng, Shandong, China.
authors: Huanli
authors: H
authors: Dong
authors: Department of Anesthesiology, Liaocheng People's Hospital, Liaocheng, Shandong, China. Electronic address: zwzhang68@sina.com.
authors: Zongwang
authors: Z
authors: Zhang
authors: Department of Anesthesiology, Affiliated Hospital of Qingdao University Medical College, Qingdao, Shandong, China.
authors: Shilei
authors: S
authors: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D045304:Cytochromes c / Q000378:metabolism; D019610:Cytoprotection; D003981:Diazoxide / Q000494:pharmacology*; D004195:Disease Models, Animal; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013096:Spermine / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D015220:Calcium Channels; D018696:Neuroprotective Agents; C034703:mitochondrial calcium uniporter; D013096:Spermine; D045304:Cytochromes c; D003981:Diazoxide
keywords: Diazoxide; apoptosis; mitochondria; spermine