title: Reperfusion promotes mitochondrial biogenesis following focal cerebral ischemia in rats.
abstract: OBJECTIVE
  Reperfusion after transient cerebral ischemia causes severe damage to mitochondria; however, little is known regarding the continuous change in mitochondrial biogenesis during reperfusion. Mitochondrial biogenesis causes an increase in the individual mitochondrial mass of neurons and maintains their aerobic set-point in the face of declining function. The aim of this study was to examine mitochondrial biogenesis in the cortex during reperfusion following focal cerebral ischemia.
  
  
  METHODS
  Male Wistar rats were subjected to transient focal cerebral ischemia. The relative amount of cortical mitochondrial DNA was analyzed using quantitative real-time PCR at 0 h, 24 h, 72 h, and 7 d after reperfusion. Three critical transcriptional regulators of mitochondrial biogenesis were measured by semi-quantitative reverse-transcription PCR. The protein expression of cytochrome C oxidase subunits I and IV was detected by Western blotting.
  
  
  RESULTS
  Evidence of increased mitochondrial biogenesis was observed after reperfusion. The cortical mitochondrial DNA content increased after 24 h, peaked after 72 h, and maintained a high level for 7 d. The cortical expression of three critical genes for the transcriptional regulation of mitochondrial biogenesis, namely, peroxisome proliferator-activated receptor coactivator-1α, nuclear respiratory factor-1, and mitochondrial transcription factor A, also increased at 24 h and 72 h. The expression of peroxisome proliferator-activated receptor coactivator-1α returned to the baseline level at 7 d, but two other factors maintained higher levels compared with the controls. Moreover, the expression of cytochrome C oxidase subunits I and IV was increased in the cortex.
  
  
  CONCLUSIONS
  These results indicate that reperfusion increased mitochondrial biogenesis following focal cerebral ischemia, and this tendency was exacerbated as the reperfusion time was extended. Reperfusion-induced mitochondrial biogenesis was mediated through up-regulation of critical transcriptional regulators of mitochondrial biogenesis.
authors.affiliation: Department of Anesthesiology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Yuying
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Anesthesiology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Guibo
authors.initials: G
authors.lastname: Fan
authors.affiliation: Department of Anesthesiology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Sihua
authors.initials: S
authors.lastname: Qi
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002950:Citrate (si)-Synthase / Q000235:genetics / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D008297:Male; D063269:Mitochondrial Turnover / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D015424:Reperfusion; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004272:DNA, Mitochondrial; D012333:RNA, Messenger; D003576:Electron Transport Complex IV; D002950:Citrate (si)-Synthase