TY - JOUR
T1 - Inhibition of mammalian target of rapamycin improves neurobehavioral deficit and modulates immune response after intracerebral hemorrhage in rat
AU - Lu, Qin
AU - Gao, Lu
AU - Huang, Lijie
AU - Ruan, Linhui
AU - Yang, Jianjing
AU - Huang, Weilong
AU - Li, Zhenxing
AU - Zhang, Yongliang
AU - Jin, Kunlin
AU - Zhuge, Qichuan
N1 - Funding Information:
The study was supported by a grant from the National Natural Science foundation of China (No. 81171088). We are grateful to Professor Dong-Ming Su (University of North Texas Health Science Center, USA) for critical suggestions on the experiments.
PY - 2014/3/6
Y1 - 2014/3/6
N2 - 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-β and reduced interferon-γ both in peripheral blood and brain. Conclusions: Our study suggests that mTOR improves ICH outcome and modulates immune response after ICH.
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-β and reduced interferon-γ both in peripheral blood and brain. Conclusions: Our study suggests that mTOR improves ICH outcome and modulates immune response after ICH.
KW - ICH
KW - Immune response
KW - Outcome
KW - Rapamycin
KW - mTOR
UR - http://www.scopus.com/inward/record.url?scp=84897957477&partnerID=8YFLogxK
U2 - 10.1186/1742-2094-11-44
DO - 10.1186/1742-2094-11-44
M3 - Article
C2 - 24602288
AN - SCOPUS:84897957477
VL - 11
JO - Journal of Neuroinflammation
JF - Journal of Neuroinflammation
SN - 1742-2094
M1 - 44
ER -