PMID- 28808420
OWN - NLM
STAT- MEDLINE
DCOM- 20180504
LR  - 20211204
IS  - 1449-2288 (Electronic)
IS  - 1449-2288 (Linking)
VI  - 13
IP  - 7
DP  - 2017
TI  - Inhibition of mTOR signaling Confers Protection against Cerebral Ischemic Injury 
      in Acute Hyperglycemic Rats.
PG  - 878-887
LID - 10.7150/ijbs.18976 [doi]
AB  - Hyperglycemia is known to exacerbate neuronal death resulted from cerebral 
      ischemia. The mechanisms are not fully understood. The mammalian target of 
      rapamycin (mTOR) pathway regulates cell growth, division and apoptosis. Recent 
      studies suggest that activation of mTOR may mediate ischemic brain damage. The 
      objective of the present experiment is to explore whether mTOR mediates ischemic 
      brain damage in acute hyperglycemic animals. Rats were subjected to 10 min of 
      forebrain ischemia under euglycemic, hyperglycemic and rapamycin-treated 
      hyperglycemic conditions. The rat brain samples were collected from the cortex 
      and hippocampi after 3h and 16h of reperfusion. The results showed that 
      hyperglycemia significantly increased neuronal death in the cortex and 
      hippocampus and the exacerbation effect of hyperglycemia was associated with 
      further activation of mTOR under control and/or ischemic conditions. Inhibition 
      of mTOR with rapamycin ameliorated the damage and suppressed 
      hyperglycemia-elevated p-MTOR, p-P70S6K and p-S6. In addition, hyperglycemia per 
      se increased the levels of cytosolic cytochrome c and autophagy marker LC3-II, 
      while rapamycin alleviated these alterations. It is concluded that activation of 
      mTOR signaling may play a detrimental role in mediating the aggravating effect of 
      hyperglycemia on cerebral ischemia.
FAU - Hei, Changchun
AU  - Hei C
AD  - Key Laboratory of Craniocerebral Diseases of Ningxia Hui Autonomous Region and 
      Department Human Anatomy, Histology and Embryology, Ningxia Medical University, 
      Yinchuan 750004, China.
AD  - Department of Pharmaceutical Sciences, Biomanufacturing Research Institute 
      Biotechnology Enterprise (BRITE), North Carolina Central University, 1801 
      Fayetteville Street, Durham, NC 27707, USA.
FAU - Liu, Ping
AU  - Liu P
AD  - Department of Endocrinology, General Hospital of Ningxia Medical University, 
      Yinchuan 750004, China.
AD  - Department of Pharmaceutical Sciences, Biomanufacturing Research Institute 
      Biotechnology Enterprise (BRITE), North Carolina Central University, 1801 
      Fayetteville Street, Durham, NC 27707, USA.
FAU - Yang, Xiao
AU  - Yang X
AD  - Department of Pharmaceutical Sciences, Biomanufacturing Research Institute 
      Biotechnology Enterprise (BRITE), North Carolina Central University, 1801 
      Fayetteville Street, Durham, NC 27707, USA.
AD  - Neuroscience Center, General Hospital of Ningxia Medical University, and Key 
      Laboratory of Craniocerebral Diseases of Ningxia Hui Autonomous Region, Yinchuan 
      750004, China.
FAU - Niu, Jianguo
AU  - Niu J
AD  - Key Laboratory of Craniocerebral Diseases of Ningxia Hui Autonomous Region and 
      Department Human Anatomy, Histology and Embryology, Ningxia Medical University, 
      Yinchuan 750004, China.
FAU - Li, P Andy
AU  - Li PA
AD  - Department of Pharmaceutical Sciences, Biomanufacturing Research Institute 
      Biotechnology Enterprise (BRITE), North Carolina Central University, 1801 
      Fayetteville Street, Durham, NC 27707, USA.
LA  - eng
PT  - Journal Article
DEP - 20170707
PL  - Australia
TA  - Int J Biol Sci
JT  - International journal of biological sciences
JID - 101235568
RN  - 0 (Immunosuppressive Agents)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Brain Ischemia/*prevention & control
MH  - Hyperglycemia/*chemically induced/complications
MH  - Immunosuppressive Agents/pharmacology
MH  - Male
MH  - Random Allocation
MH  - Rats
MH  - Rats, Wistar
MH  - Signal Transduction/*physiology
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/genetics/*metabolism
PMC - PMC5555105
OTO - NOTNLM
OT  - Cerebral ischemia
OT  - Hyperglycemia
OT  - Pathology
OT  - Rapamycin
OT  - Rat.
OT  - mTOR
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2017/08/16 06:00
MHDA- 2018/05/05 06:00
PMCR- 2017/01/01
CRDT- 2017/08/16 06:00
PHST- 2016/12/29 00:00 [received]
PHST- 2017/01/28 00:00 [accepted]
PHST- 2017/08/16 06:00 [entrez]
PHST- 2017/08/16 06:00 [pubmed]
PHST- 2018/05/05 06:00 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - ijbsv13p0878 [pii]
AID - 10.7150/ijbs.18976 [doi]
PST - epublish
SO  - Int J Biol Sci. 2017 Jul 7;13(7):878-887. doi: 10.7150/ijbs.18976. eCollection 
      2017.