[Immunomodulation by inducing tolerance to E-selectin and adult neurogenesis after stroke].
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| Abstract |
Neuroblasts in the subventricular zone proliferate markedly after stroke, and migrate to the site of injury along with blood vessels. However, a large fraction of stroke-generated neuroblasts die shortly after being born, because of local inflammation. E-selectin is specifically expressed on endothelial cells, but only when the endothelium activates. Since endothelial activation occurs after stroke, E-selectin can serve as an immunologic tolerization antigen that can focus immunomodulation to regions of the vascular tree. Intranasal instillation of recombinant E-selectin will induce mucosal tolerance to that antigen with the generation of E-selectin-specific regulatory T cells (Tregs). Tregs may protect newly-generated neuroblasts from ischemic damage through 'bystander suppression' in which immunomodulatory cytokines such as TGF-β and IL-10 are released locally. In this series of experiments, we have shown that after E-selectin tolerization in permanent middle cerebral artery occlusion (pMCAO) rats Tregs transmigrate to the peri-infarct region of ischemic brain, TNF expression in the local neurovascular niche is reduced, and the survival of newly generated neuroblasts or neurons in the peri-infarct region is increased. Under these conditions, an improvement in sensorimotor function after pMCAO also occurs. E-selectin-specific Tregs can modulate the efficacy of adult neurogenesis after ischemia and promote repair after brain injury.
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| Authors | Satoru Ishibashi |
| Journal | Rinsho shinkeigaku = Clinical neurology (Rinsho Shinkeigaku) Vol. 50 Issue 11 Pg. 882-5 (Nov 2010) ISSN: 1882-0654 [Electronic] Japan |
| PMID | 21921488 (Publication Type: English Abstract, Journal Article, Review) |
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