PMID- 27026509
OWN - NLM
STAT- MEDLINE
DCOM- 20170217
LR  - 20220318
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Mar 30
TI  - Pramipexole-Induced Hypothermia Reduces Early Brain Injury via PI3K/AKT/GSK3beta 
      pathway in Subarachnoid Hemorrhage rats.
PG  - 23817
LID - 10.1038/srep23817 [doi]
LID - 23817
AB  - Previous studies have shown neuroprotective effects of hypothermia. However, its 
      effects on subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) remain 
      unclear. In this study, a SAH rat model was employed to study the effects and 
      mechanisms of pramipexole-induced hypothermia on EBI after SAH. Dose-response 
      experiments were performed to select the appropriate pramipexole concentration 
      and frequency of administration for induction of mild hypothermia (33-36  degrees C). 
      Western blot, neurobehavioral evaluation, Terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL) and Fluoro-Jade B (FJB) 
      staining were used to detect the effects of pramipexole-induced hypothermia on 
      SAH-induced EBI, as well as to study whether controlled rewarming could attenuate 
      these effects. Inhibitors targeting the PI3K/AKT/GSK3beta pathway were administered 
      to determine whether the neuroprotective effect of pramipexole-induced 
      hypothermia was mediated by PI3K/AKT/GSK3beta signaling pathway. The results showed 
      that intraperitoneal injection of pramipexole at 0.25 body weight once per 8 
      hours was found to successfully and safely maintain rats at mild hypothermia. 
      Pramipexole-induced hypothermia ameliorated SAH-induced brain cell death, 
      blood-brain barrier damage and neurobehavioral deficits in a PI3K/AKT/GSK3beta 
      signaling-dependent manner. Therefore, we may conclude that pramipexole-induced 
      hypothermia could effectively inhibit EBI after SAH in rats via PI3K/AKT/GSK3beta 
      signaling pathway.
FAU - Ma, Junwei
AU  - Ma J
AD  - Department of Neurosurgery &Brain and Nerve Research Laboratory, The First 
      Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, 
      China.
AD  - Department of Neurosurgery, Suzhou Kowloon Hospital Affiliated Shanghai Jiao Tong 
      University, Suzhou, 266021, China.
FAU - Wang, Zhong
AU  - Wang Z
AD  - Department of Neurosurgery &Brain and Nerve Research Laboratory, The First 
      Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, 
      China.
FAU - Liu, Chenglin
AU  - Liu C
AD  - Department of Neurosurgery &Brain and Nerve Research Laboratory, The First 
      Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, 
      China.
FAU - Shen, Haitao
AU  - Shen H
AD  - Department of Neurosurgery &Brain and Nerve Research Laboratory, The First 
      Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, 
      China.
FAU - Chen, Zhouqing
AU  - Chen Z
AD  - Department of Neurosurgery &Brain and Nerve Research Laboratory, The First 
      Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, 
      China.
FAU - Yin, Jia
AU  - Yin J
AD  - Department of Neurosurgery &Brain and Nerve Research Laboratory, The First 
      Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, 
      China.
FAU - Zuo, Gang
AU  - Zuo G
AD  - Department of Neurosurgery &Brain and Nerve Research Laboratory, The First 
      Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, 
      China.
FAU - Duan, Xiaochun
AU  - Duan X
AD  - Department of Neurosurgery &Brain and Nerve Research Laboratory, The First 
      Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, 
      China.
FAU - Li, Haiying
AU  - Li H
AD  - Department of Neurosurgery &Brain and Nerve Research Laboratory, The First 
      Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, 
      China.
FAU - Chen, Gang
AU  - Chen G
AD  - Department of Neurosurgery &Brain and Nerve Research Laboratory, The First 
      Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160330
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Benzothiazoles)
RN  - 0 (Neuroprotective Agents)
RN  - 83619PEU5T (Pramipexole)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Gsk3b protein, rat)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Benzothiazoles/*pharmacology/therapeutic use
MH  - Blood-Brain Barrier/metabolism
MH  - Brain/blood supply/drug effects/pathology
MH  - Drug Evaluation, Preclinical
MH  - Glycogen Synthase Kinase 3 beta/metabolism
MH  - Hypothermia, Induced
MH  - Male
MH  - Neuroprotective Agents/*pharmacology/therapeutic use
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Pramipexole
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction
MH  - Subarachnoid Hemorrhage/metabolism/pathology/*therapy
PMC - PMC4812308
EDAT- 2016/03/31 06:00
MHDA- 2017/02/18 06:00
PMCR- 2016/03/30
CRDT- 2016/03/31 06:00
PHST- 2015/08/18 00:00 [received]
PHST- 2016/03/15 00:00 [accepted]
PHST- 2016/03/31 06:00 [entrez]
PHST- 2016/03/31 06:00 [pubmed]
PHST- 2017/02/18 06:00 [medline]
PHST- 2016/03/30 00:00 [pmc-release]
AID - srep23817 [pii]
AID - 10.1038/srep23817 [doi]
PST - epublish
SO  - Sci Rep. 2016 Mar 30;6:23817. doi: 10.1038/srep23817.