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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2014

Open Access 01-12-2014 | Research

Inhibition of mammalian target of rapamycin improves neurobehavioral deficit and modulates immune response after intracerebral hemorrhage in rat

Authors: Qin Lu, Lu Gao, Lijie Huang, Linhui Ruan, Jianjing Yang, Weilong Huang, Zhenxing Li, Yongliang Zhang, Kunlin Jin, Qichuan Zhuge

Published in: Journal of Neuroinflammation | Issue 1/2014

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Abstract

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.
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Metadata
Title
Inhibition of mammalian target of rapamycin improves neurobehavioral deficit and modulates immune response after intracerebral hemorrhage in rat
Authors
Qin Lu
Lu Gao
Lijie Huang
Linhui Ruan
Jianjing Yang
Weilong Huang
Zhenxing Li
Yongliang Zhang
Kunlin Jin
Qichuan Zhuge
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2014
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-11-44

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