PMID- 30222190 OWN - NLM STAT- MEDLINE DCOM- 20190205 LR - 20190215 IS - 1098-2299 (Electronic) IS - 0272-4391 (Linking) VI - 79 IP - 6 DP - 2018 Sep TI - Neuroprotection of rhGLP-1 in diabetic rats with cerebral ischemia/reperfusion injury via regulation of oxidative stress, EAAT2, and apoptosis. PG - 249-259 LID - 10.1002/ddr.21439 [doi] AB - Preclinical Research & Development The purpose of the present study is to evaluate the neuroprotective effect of recombinant human glucagon-like peptide-1 (rhGLP-1) as well as to explore corresponding mechanisms in diabetic rats with cerebral ischemia/reperfusion injury induced by middle cerebral artery occlusion (MCAO). Diabetes mellitus was induced by intraperitoneal injection of streptozotocin. The rats were pretreated with rhGLP-1 (20 mug/kg intraperitoneally, thrice a day) for 14 days. Thereafter, the rats were subjected to MCAO 90 min/reperfusion 24 hr. At 2 and 24 hr of reperfusion, the rats were assessed for neurological deficits and subsequently executed for the evaluation of cerebral infarct volume, oxidative stress parameters, and the expression of excitatory amino acid transporter 2 (EAAT2) and apoptotic markers. Results indicate that rhGLP-1 significantly ameliorated neurological deficits and reduced cerebral infarct volume in diabetic MCAO rats. In addition, oxidative stress parameters in ischemic penumbra were significantly alleviated in rhGLP-1-pretreated diabetic MCAO rats. rhGLP-1 significantly upregulated the ratio of Bcl-2/Bax and EAAT2 expression and downregulated cleaved caspase-3 expression in ischemic penumbra of diabetic MCAO rats. Our results suggest that rhGLP-1 could significantly ameliorate neurological deficits and reduce cerebral infarct volume in diabetic MCAO rats, which may be due to the inhibition of oxidative stress and apoptosis and the promotion of EAAT2 expression. CI - (c) 2018 Wiley Periodicals, Inc. FAU - Fang, Yi AU - Fang Y AD - Department of Pharmacy, Peking University People's Hospital, Beijing, People's Republic of China. FAU - Jiang, Daoli AU - Jiang D AUID- ORCID: 0000-0002-5566-6585 AD - Department of Pharmacy, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People's Republic of China. FAU - Wang, Yitong AU - Wang Y AD - Department of Pharmacy, Peking University People's Hospital, Beijing, People's Republic of China. AD - Department of Pharmacy Administration and Clinical Pharmacy, Peking University Health Science Center, Beijing, People's Republic of China. FAU - Wang, Qian AU - Wang Q AD - Department of Pharmacy, Peking University People's Hospital, Beijing, People's Republic of China. FAU - Lv, Dongmei AU - Lv D AD - Department of Pharmacy, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People's Republic of China. FAU - Liu, Jichao AU - Liu J AD - Animal Experimental Center, Peking University People's Hospital, Beijing, People's Republic of China. FAU - Liu, Chang AU - Liu C AD - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, People's Republic of China. LA - eng GR - No: 2013-22/Peking University People's Hospital Research and Development Funds/International GR - Peking University/International GR - Research and Development/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180917 PL - United States TA - Drug Dev Res JT - Drug development research JID - 8204468 RN - 0 (Excitatory Amino Acid Transporter 2) RN - 0 (Incretins) RN - 0 (Neuroprotective Agents) RN - 0 (Recombinant Proteins) RN - 0 (Slc1a2 protein, rat) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Brain Ischemia/complications/*drug therapy MH - Diabetes Complications/drug therapy/physiopathology MH - Diabetes Mellitus/*drug therapy/physiopathology MH - Excitatory Amino Acid Transporter 2/metabolism MH - Glucagon-Like Peptide 1/*genetics/*pharmacology MH - Humans MH - Incretins/*pharmacology MH - Infarction, Middle Cerebral Artery MH - Neuroprotective Agents MH - Oxidative Stress/drug effects MH - Rats MH - Recombinant Proteins/*pharmacology MH - Reperfusion Injury/complications/drug therapy/physiopathology OTO - NOTNLM OT - cerebral ischemia/reperfusion injury OT - diabetes OT - rhGLP-1 EDAT- 2018/09/18 06:00 MHDA- 2019/02/06 06:00 CRDT- 2018/09/18 06:00 PHST- 2018/01/30 00:00 [received] PHST- 2018/06/05 00:00 [revised] PHST- 2018/06/07 00:00 [accepted] PHST- 2018/09/18 06:00 [pubmed] PHST- 2019/02/06 06:00 [medline] PHST- 2018/09/18 06:00 [entrez] AID - 10.1002/ddr.21439 [doi] PST - ppublish SO - Drug Dev Res. 2018 Sep;79(6):249-259. doi: 10.1002/ddr.21439. Epub 2018 Sep 17.