PMID- 31647899
OWN - NLM
STAT- MEDLINE
DCOM- 20210329
LR  - 20210329
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1726
DP  - 2020 Jan 1
TI  - Chloroquine pretreatment attenuates ischemia-reperfusion injury in the brain of 
      ob/ob diabetic mice as well as wildtype mice.
PG  - 146518
LID - S0006-8993(19)30572-4 [pii]
LID - 10.1016/j.brainres.2019.146518 [doi]
AB  - Chloroquine, a prototype anti-malaria drug, has been reported to possess 
      anti-inflammatory effects. Moreover, chloroquine pretreatment could improve DNA 
      damage repair. It is therefore reasonable to hypothesize that chloroquine 
      pretreatment could attenuate ischemia/reperfusion injury in the brain. 
      Considering the fact that chloroquine could also improve glucose metabolism, we 
      speculated that the potential effects of chloroquine on ischemia/reperfusion 
      injury might be particularly pronounced in diabetic mice. In this study, 
      chloroquine pretreatment protected neurons from Oxygen Glucose Deprivation (OGD) 
      induced cytotoxicity and apoptosis. In vivo, Ob/ob mice and wildtype (WT) mice 
      were pretreated with chloroquine for 3 weeks. Then, ischemic stroke was induced 
      by 60 min Middle Cerebral Artery Occlusion (MCAO). We found that chloroquine 
      pretreatment normalized blood glucose in diabetic ob/ob mice, and reduced 
      cerebral damage after ischemic stroke especially for diabetic mice. In addition, 
      chloroquine pretreatment reduced High-mobility group box 1 (HMGB1) content in the 
      cerebrospinal fluid (CSF) and serum and lowered myeloperoxidase (MPO) activity 
      and inflammatory cytokines gene expression both in the ob/ob diabetic mice and WT 
      mice. Moreover, harmful DNA damage-signaling responses, including PARP activation 
      and p53 activation, were also attenuated by chloroquine pretreatment in these two 
      kinds of mice. In conclusion, chloroquine pretreatment could reduce cerebral 
      damage after ischemic stroke especially in diabetic mice through multiple 
      mechanisms, which include reducing neural cell DNA injury, restoring euglycemia 
      and anti-inflammatory effects. The findings may provide potential for the 
      development of chloroquine in the prevention and treatment of stroke in diabetic 
      high-risk patients.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Zhang, Ying-Pei
AU  - Zhang YP
AD  - Department of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan 430071, 
      China.
FAU - Cui, Qiu-Yan
AU  - Cui QY
AD  - Department of Physiology, School of Basic Medicine and Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 4030030, China; The 
      Institute for Brain Research, Collaborative Innovation Center for Brain Science, 
      Huazhong University of Science and Technology, Wuhan 430030, China.
FAU - Zhang, Tong-Mei
AU  - Zhang TM
AD  - Department of Physiology, School of Basic Medicine and Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 4030030, China; The 
      Institute for Brain Research, Collaborative Innovation Center for Brain Science, 
      Huazhong University of Science and Technology, Wuhan 430030, China.
FAU - Yi, Yao
AU  - Yi Y
AD  - Department of Physiology, School of Basic Medicine and Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 4030030, China; The 
      Institute for Brain Research, Collaborative Innovation Center for Brain Science, 
      Huazhong University of Science and Technology, Wuhan 430030, China.
FAU - Nie, Jun-Jie
AU  - Nie JJ
AD  - Department of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan 430071, 
      China.
FAU - Xie, Guang-Hui
AU  - Xie GH
AD  - Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan 430071, 
      China.
FAU - Wu, Jian-Hua
AU  - Wu JH
AD  - Department of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan 430071, 
      China. Electronic address: jhwu@whu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191021
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Blood Glucose)
RN  - 0 (HMGB1 Protein)
RN  - 0 (HMGB1 protein, mouse)
RN  - 0 (Neuroprotective Agents)
RN  - 886U3H6UFF (Chloroquine)
SB  - IM
MH  - Animals
MH  - Blood Glucose/drug effects
MH  - Brain/*drug effects/pathology/physiopathology
MH  - Brain Ischemia/*physiopathology/prevention & control
MH  - Cell Survival/drug effects
MH  - Chloroquine/*administration & dosage
MH  - Diabetes Mellitus/*physiopathology
MH  - Disease Models, Animal
MH  - HMGB1 Protein/cerebrospinal fluid
MH  - Mice, Inbred C57BL
MH  - Neurons/drug effects/pathology/physiology
MH  - Neuroprotective Agents/*administration & dosage
MH  - Primary Cell Culture
MH  - Reperfusion Injury/*physiopathology/prevention & control
OTO - NOTNLM
OT  - Chloroquine
OT  - Diabetes
OT  - Stroke
EDAT- 2019/10/28 06:00
MHDA- 2021/03/30 06:00
CRDT- 2019/10/25 06:00
PHST- 2019/06/25 00:00 [received]
PHST- 2019/09/15 00:00 [revised]
PHST- 2019/10/19 00:00 [accepted]
PHST- 2019/10/28 06:00 [pubmed]
PHST- 2021/03/30 06:00 [medline]
PHST- 2019/10/25 06:00 [entrez]
AID - S0006-8993(19)30572-4 [pii]
AID - 10.1016/j.brainres.2019.146518 [doi]
PST - ppublish
SO  - Brain Res. 2020 Jan 1;1726:146518. doi: 10.1016/j.brainres.2019.146518. Epub 2019 
      Oct 21.