Rinsho Shinkeigaku (Clinical Neurology)

The 51st Annual Meeting of the Japanese Society of Neurology

Immunomodulation by inducing tolerance to E-selectin and adult neurogenesis after stroke

Satoru Ishibashi, M.D., Ph.D.

Department of Neurology, Tokyo Medical and Dental University Hospital, Tokyo Medical and Dental University

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.
Full Text of this Article in Japanese PDF (465K)

(CLINICA NEUROL, 50: 882|885, 2010)
key words: adult neurogenesis, immunomodulation, E-selectin, regulatory T cell, stroke

(Received: 21-May-10)