title: Neuroprotection from stroke in the absence of MHCI or PirB.
abstract: Recovery from stroke engages mechanisms of neural plasticity. Here we examine a role for MHC class I (MHCI) H2-Kb and H2-Db, as well as PirB receptor. These molecules restrict synaptic plasticity and motor learning in the healthy brain. Stroke elevates neuronal expression not only of H2-Kb and H2-Db, but also of PirB and downstream signaling. KbDb knockout (KO) or PirB KO mice have smaller infarcts and enhanced motor recovery. KO hippocampal organotypic slices, which lack an intact peripheral immune response, have less cell death after in vitro ischemia. In PirB KO mice, corticospinal projections from the motor cortex are enhanced, and the reactive astrocytic response is dampened after MCAO. Thus, molecules that function in the immune system act not only to limit synaptic plasticity in healthy neurons, but also to exacerbate brain injury after ischemia. These results suggest therapies for stroke by targeting MHCI and PirB.
authors.affiliation: Department of Biology and Neurobiology, Stanford University, Stanford, CA 94305-5437, USA.
authors.forename: Jaimie D
authors.initials: JD
authors.lastname: Adelson
authors.forename: George E
authors.initials: GE
authors.lastname: Barreto
authors.forename: Lijun
authors.initials: L
authors.lastname: Xu
authors.forename: Taeho
authors.initials: T
authors.lastname: Kim
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Brott
authors.forename: Yi-Bing
authors.initials: YB
authors.lastname: Ouyang
authors.forename: Thorsten
authors.initials: T
authors.lastname: Naserke
authors.forename: Maja
authors.initials: M
authors.lastname: Djurisic
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Xiong
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Shatz
authors.forename: Rona G
authors.initials: RG
authors.lastname: Giffard
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology; D001710:Biotin / Q000031:analogs & derivatives; D001921:Brain / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D003911:Dextrans; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000378:metabolism; D009043:Motor Activity / Q000235:genetics; D009044:Motor Cortex / Q000473:pathology; D009924:Organ Culture Techniques; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011712:Pyramidal Tracts / Q000473:pathology; D011971:Receptors, Immunologic / Q000172:deficiency* / Q000235:genetics; D020127:Recovery of Function / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D013997:Time Factors
chemical_list: C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D003911:Dextrans; D005904:Glial Fibrillary Acidic Protein; D015395:Histocompatibility Antigens Class I; D008840:Microfilament Proteins; C105949:Pirb protein, mouse; D011971:Receptors, Immunologic; C076397:biotinylated dextran amine; D001710:Biotin; D010751:Phosphopyruvate Hydratase