title: Post-ischemia mdivi-1 treatment protects against ischemia/reperfusion-induced brain injury in a rat model.
abstract: When given prior to brain ischemia, mitochondrial division inhibitor-1 (mdivi-1) attenuates the brain damage caused by ischemia. Here, we investigated the potential effects of post-ischemia mdivi-1 treatment (1mg/kg, i.p., administered immediately after 2h of ischemia and prior to reperfusion) using a MCAO rat model. Mdivi-1 treatment decreased infarct volume and improved neurological function. In addition, cytochrome C release was attenuated, and neuronal apoptosis was decreased. The mitochondrial fission protein dynamin-related protein 1 (Drp1) was decreased in the mitochondrial fraction but increased in the cytosolic fraction. Mdivi-1 treatment augmented the increases in the mRNA expression of peroxisome proliferator-activated receptor coactivator-1α, nuclear respiratory factor-1, and mitochondrial transcriptional factor A. In conclusion, when given after ischemia and prior to reperfusion, mdivi-1 can protect against brain damage by inhibiting the mitochondria-mediated apoptosis induced by mitochondrial fission. Post-ischemia mdivi-1 treatment might promote I/R-induced mitochondrial biogenesis.
authors.affiliation: Department of Anesthesiology, Fourth Affiliated Hospital, Harbin Medical University, 37 Yiyuan Street, Nangang District, Harbin 150001, China; School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Anesthesiology, Fourth Affiliated Hospital, Harbin Medical University, 37 Yiyuan Street, Nangang District, Harbin 150001, China.
authors.forename: Yuying
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Nephrology, Fifth Hospital in Harbin, 27 Jiankang Road, Xiangfang District, Harbin 150001, China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Fourth Affiliated Hospital, Harbin Medical University, 37 Yiyuan Street, Nangang District, Harbin 150001, China.
authors.forename: Baoqing
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of Anesthesiology, Fourth Affiliated Hospital, Harbin Medical University, 37 Yiyuan Street, Nangang District, Harbin 150001, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Fourth Affiliated Hospital, Harbin Medical University, 37 Yiyuan Street, Nangang District, Harbin 150001, China. Electronic address: sihuaqi_2013@163.com.
authors.forename: Sihua
authors.initials: S
authors.lastname: Qi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D034281:Dynamins / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D063154:Mitochondrial Dynamics / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001678:Organelle Biogenesis; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism; D052999:Quinazolinones / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
chemical_list: C549041:3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinone; D018696:Neuroprotective Agents; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D052999:Quinazolinones; D045304:Cytochromes c; C519851:Dnm1l protein, rat; D034281:Dynamins
keywords: Ischemia/reperfusion; Mitochondrial biogenesis; Mitochondrial division inhibitor-1 (mdivi-1); Mitochondrial fission; Peroxisome proliferator-activated receptor coactivator-1α (PGC-1α)