title: Ischemic postconditioning protects against focal cerebral ischemia by inhibiting brain inflammation while attenuating peripheral lymphopenia in mice.
abstract: BACKGROUND
  Ischemic postconditioning (IPostC) has been shown to attenuate brain injury in rat stroke models, but a mouse model has not been reported. This study establishes an IPostC model in mice and investigates how IPostC affects infiltration of leukocytes in the ischemic brain and lymphopenia associated with stroke-induced immunodepression.
  
  
  METHODS
  A total of 125 mice were used. IPostC was performed by a repeated series of brief occlusions of the middle cerebral artery (MCA) after reperfusion, in a focal ischemia model in mice. Infarct sizes, neurological scores, inflammatory brain cells and immune cell populations in lymph nodes, spleen and bone marrow were analyzed with fluorescence-activated cell sorting (FACS).
  
  
  RESULTS
  IPostC performed immediately, 2 min and 3 h after reperfusion significantly reduced infarct sizes and attenuated neurological scores as measured up to 3 days post-stroke. In the group with strongest protection, infarct sizes were reduced from 49.6±2.8% (n=16) to 27.9±2.9% (n=10, P<.001). The spared infarct areas were seen in the ischemic penumbra or ischemic margins, i.e., the border zones between the cortical territories of the anterior cerebral artery and those of the MCA, as well as in the ventromedial and dorsolateral striata. FACS analyses showed that IPostC significantly blocked increases in the numbers of microglia (CD45intCD11b+), macrophages (CD45hiCD68+), CD4 T cells (CD45+CD4+) and CD8 T cells (CD45+CD8+) as well as B lymphocytes (CD45+CD19+) in the ischemic brain (n=5/group). Reduced-immune cell numbers in the peripheral blood and spleen were increased by IPostC while immune cell populations in the bone marrow were not altered by IPostC.
  
  
  CONCLUSIONS
  IPostC reduced brain infarction and mitigated neurological deficits in mice, likely by blocking infiltration of both innate and adaptive immune cells in the ischemic brain. In addition, IPostC robustly attenuated peripheral lymphopenia and thus improved systemic immunodepression.
authors.affiliation: Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305-5327, USA.
authors.forename: S P
authors.initials: SP
authors.lastname: Joo
authors.forename: W
authors.initials: W
authors.lastname: Xie
authors.forename: X
authors.initials: X
authors.lastname: Xiong
authors.forename: B
authors.initials: B
authors.lastname: Xu
authors.forename: H
authors.initials: H
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D002469:Cell Separation; D004195:Disease Models, Animal; D004660:Encephalitis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D005434:Flow Cytometry; D057775:Ischemic Postconditioning / Q000379:methods*; D008231:Lymphopenia / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D051379:Mice