title: Rapamycin Reduced Ischemic Brain Damage in Diabetic Animals Is Associated with Suppressions of mTOR and ERK1/2 Signaling.
abstract: The objectives of the present study are to investigate the activation of mTOR and ERK1/2 signaling after cerebral ischemia in diabetic rats and to examine the neuroprotective effects of rapamycin. Ten minutes transient global cerebral ischemia was induced in straptozotocin-induced diabetic hyperglycemic rats and non-diabetic, euglycemic rats. Brain samples were harvested after 16 h of reperfusion. Rapamycin or vehicle was injected 1 month prior to the induction of ischemia. The results showed that diabetes increased ischemic neuronal cell death and associated with elevations of p-P70S6K and Ras/ERK1/2 and suppression of p-AMPKα. Rapamycin ameliorated diabetes-enhanced ischemic brain damage and suppressed phosphorylation of P70S6K and ERK1/2. It is concluded that diabetes activates mTOR and ERK1/2 signaling pathways in rats subjected to transient cerebral ischemia and inhibition of mTOR by rapamycin reduces ischemic brain damage and suppresses the mTOR and ERK1/2 signaling in diabetic settings.
authors.affiliation: 1. Department of Endocrinology, General Hospital of Ningxia Medical University, Yinchuan 750004, China; 2. Department of Pharmaceutical Sciences, Biomanufacturing Research Institute Biotechnology Enterprise (BRITE), North Carolina Central University, 1801 Fayetteville Street, Durham, NC 27707, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: 3. Neuroscience Center, General Hospital of Ningcia Medical University, and Key Laboratory of Craniocerebral Diseases of Ningxia Hui Autonomous Region, Yinchuan 750004, China; 2. Department of Pharmaceutical Sciences, Biomanufacturing Research Institute Biotechnology Enterprise (BRITE), North Carolina Central University, 1801 Fayetteville Street, Durham, NC 27707, USA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: 2. Department of Pharmaceutical Sciences, Biomanufacturing Research Institute Biotechnology Enterprise (BRITE), North Carolina Central University, 1801 Fayetteville Street, Durham, NC 27707, USA; 4. Department of Human Anatomy, Histology and Embryology, Ningxia Medical University, Yinchuan 75004, China.
authors.forename: Changchun
authors.initials: C
authors.lastname: Hei
authors.affiliation: 2. Department of Pharmaceutical Sciences, Biomanufacturing Research Institute Biotechnology Enterprise (BRITE), North Carolina Central University, 1801 Fayetteville Street, Durham, NC 27707, USA.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Meli
authors.affiliation: 4. Department of Human Anatomy, Histology and Embryology, Ningxia Medical University, Yinchuan 75004, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Niu
authors.affiliation: 4. Department of Human Anatomy, Histology and Embryology, Ningxia Medical University, Yinchuan 75004, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.affiliation: 2. Department of Pharmaceutical Sciences, Biomanufacturing Research Institute Biotechnology Enterprise (BRITE), North Carolina Central University, 1801 Fayetteville Street, Durham, NC 27707, USA.
authors.forename: P Andy
authors.initials: PA
authors.lastname: Li
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D015153:Blotting, Western; D002545:Brain Ischemia / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020123:Sirolimus / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D020123:Sirolimus
keywords: Cerebral ischemia; Diabetes; ERK1/2; Rapamycin; mTOR