title: Inhibition of mammalian target of rapamycin improves neurobehavioral deficit and modulates immune response after intracerebral hemorrhage in rat.
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.
authors.forename: Qin
authors.initials: Q
authors.lastname: Lu
authors.forename: Lu
authors.initials: L
authors.lastname: Gao
authors.forename: Lijie
authors.initials: L
authors.lastname: Huang
authors.forename: Linhui
authors.initials: L
authors.lastname: Ruan
authors.forename: Jianjing
authors.initials: J
authors.lastname: Yang
authors.forename: Weilong
authors.initials: W
authors.lastname: Huang
authors.forename: Zhenxing
authors.initials: Z
authors.lastname: Li
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Kunlin
authors.initials: K
authors.lastname: Jin
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. zhugeqichuan@vip.163.com.
authors.forename: Qichuan
authors.initials: Q
authors.lastname: Zhuge
mesh_terms: D000818:Animals; D001804:Blood Transfusion, Autologous / Q000009:adverse effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000150:complications* / Q000276:immunology*; D017364:Collagenases; D003342:Corpus Striatum / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009422:Nervous System Diseases / Q000209:etiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D013997:Time Factors
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D017364:Collagenases; D020123:Sirolimus