Neuroprotection from stroke in the absence of MHCI or PirB

Neuron. 2012 Mar 22;73(6):1100-7. doi: 10.1016/j.neuron.2012.01.020. Epub 2012 Mar 21.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / pathology
  • Biotin / analogs & derivatives
  • Brain / metabolism
  • Calcium-Binding Proteins / metabolism
  • Dextrans
  • Disease Models, Animal
  • Gene Expression Regulation / genetics*
  • Glial Fibrillary Acidic Protein / metabolism
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism*
  • Infarction, Middle Cerebral Artery / pathology
  • Infarction, Middle Cerebral Artery / physiopathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microfilament Proteins / metabolism
  • Motor Activity / genetics
  • Motor Cortex / pathology
  • Organ Culture Techniques
  • Phosphopyruvate Hydratase / metabolism
  • Pyramidal Tracts / pathology
  • Receptors, Immunologic / deficiency*
  • Receptors, Immunologic / genetics
  • Recovery of Function / genetics*
  • Signal Transduction / genetics
  • Time Factors


  • Aif1 protein, mouse
  • Calcium-Binding Proteins
  • Dextrans
  • Glial Fibrillary Acidic Protein
  • Histocompatibility Antigens Class I
  • Microfilament Proteins
  • Pirb protein, mouse
  • Receptors, Immunologic
  • biotinylated dextran amine
  • Biotin
  • Phosphopyruvate Hydratase