Neuron
Volume 73, Issue 6, 22 March 2012, Pages 1100-1107
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Neuroprotection from Stroke in the Absence of MHCI or PirB

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Summary

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.

Highlights

► MHCIs and PirB receptor contribute to neuronal damage post stroke ► MHCI H2-Kb and H2-Db and PirB signaling increase post-MCAO ► Better recovery and smaller infarcts in KbDb KO or PirB KO mice ► Enhanced corticospinal projections and dampened astrocytic response in PirB KO mice

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3

These authors contributed equally to this work

4

Present address: Departamento de Nutrición y Bioquímica, Pontificia Universidad Javeriana, Bogotá D.C., Colombia