PMID- 24602288
OWN - NLM
STAT- MEDLINE
DCOM- 20140916
LR  - 20211203
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 11
DP  - 2014 Mar 6
TI  - Inhibition of mammalian target of rapamycin improves neurobehavioral deficit and 
      modulates immune response after intracerebral hemorrhage in rat.
PG  - 44
LID - 10.1186/1742-2094-11-44 [doi]
AB  - BACKGROUND: Mammalian target of rapamycin (mTOR), a serine/threonine kinase, 
      regulates many processes, including cell growth and the immune response. mTOR is 
      also dysregulated in several neurological diseases, such as traumatic brain 
      injury (TBI), stroke, and neurodegenerative disease. However, the role of mTOR in 
      intracerebral hemorrhage (ICH) remains unexplored. The aims of our study were to 
      determine whether inhibiting mTOR signaling could affect the outcome after ICH 
      and to investigate the possible underlying mechanism. METHODS: A rat ICH model 
      was induced by intracerebral injection of collagenase IV into the striatum, and 
      mTOR activation was inhibited by administration of rapamycin. mTOR signaling 
      activation was determined by western blotting. Neurobehavioral deficit after ICH 
      was determined by a set of modified Neurological Severity Scores (mNSS). The 
      levels of CD4+CD25+Foxp3+ regulatory T cells (Tregs) and cytokines were examined 
      using flow cytometry and ELISA, respectively. RESULTS: Our results demonstrated 
      thatmTOR signaling was activated 30 minutes and returned to its basal level 1 day 
      after ICH. Increased p-mTOR, which mean that mTOR signaling was activated, was 
      predominantly located around the hematoma. Rapamycin treatment significantly 
      improved the neurobehavioral deficit after ICH, increased the number of Tregs, 
      increased levels of interleukin-10 and transforming growth factor-beta and reduced 
      interferon-gamma both in peripheral blood and brain. CONCLUSIONS: Our study suggests 
      that mTOR improves ICH outcome and modulates immune response after ICH.
FAU - Lu, Qin
AU  - Lu Q
FAU - Gao, Lu
AU  - Gao L
FAU - Huang, Lijie
AU  - Huang L
FAU - Ruan, Linhui
AU  - Ruan L
FAU - Yang, Jianjing
AU  - Yang J
FAU - Huang, Weilong
AU  - Huang W
FAU - Li, Zhenxing
AU  - Li Z
FAU - Zhang, Yongliang
AU  - Zhang Y
FAU - Jin, Kunlin
AU  - Jin K
FAU - Zhuge, Qichuan
AU  - Zhuge Q
AD  - Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang, China. zhugeqichuan@vip.163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140306
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
RN  - 0 (Cytokines)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Foxp3 protein, rat)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.4.24.- (Collagenases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Blood Transfusion, Autologous/adverse effects
MH  - Cerebral Cortex/drug effects/physiology
MH  - Cerebral Hemorrhage/chemically induced/*complications/*immunology
MH  - Collagenases
MH  - Corpus Striatum/drug effects
MH  - Cytokines/*metabolism
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Forkhead Transcription Factors/metabolism
MH  - Gene Expression Regulation/drug effects
MH  - Male
MH  - Nervous System Diseases/*etiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects
MH  - Sirolimus/pharmacology
MH  - T-Lymphocytes, Regulatory/drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Time Factors
PMC - PMC3975837
EDAT- 2014/03/08 06:00
MHDA- 2014/09/17 06:00
PMCR- 2014/03/06
CRDT- 2014/03/08 06:00
PHST- 2013/09/28 00:00 [received]
PHST- 2014/02/21 00:00 [accepted]
PHST- 2014/03/08 06:00 [entrez]
PHST- 2014/03/08 06:00 [pubmed]
PHST- 2014/09/17 06:00 [medline]
PHST- 2014/03/06 00:00 [pmc-release]
AID - 1742-2094-11-44 [pii]
AID - 10.1186/1742-2094-11-44 [doi]
PST - epublish
SO  - J Neuroinflammation. 2014 Mar 6;11:44. doi: 10.1186/1742-2094-11-44.