Immunomodulation and adult neurogenesis after stroke
Project/Area Number |
21790836
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Single-year Grants |
Research Field |
Neurology
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Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
ISHIBASHI Satoru Tokyo Medical and Dental University, 医学部附属病院, 助教 (30533369)
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Project Period (FY) |
2009 – 2010
|
Project Status |
Completed (Fiscal Year 2010)
|
Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
|
Keywords | 脳血管障害 / 制御性T細胞 / E-セレクチン / 神経新生 / 神経幹細胞 / 動物モデル / 再生医療 / 神経保護 / 炎症 / リンパ球 |
Research 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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Report
(3 results)
Research Products
(28 results)
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[Journal Article] Transplantation of neuronal cells induced from human mesenchymal stem cells improves neurological functions after stroke without cell fusion2010
Author(s)
Xu H, Miki K, Ishibashi S, Inoue J, Sun L, Endo S, Sekiya I, Muneta T, Inazawa J, Dezawa M, Mizusawa H.
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Journal Title
J Neurosci Res.
Volume: 88(16)
Pages: 3598-3609
Related Report
Peer Reviewed
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[Journal Article] Transplantation of neuronal cells induced from human mesenchymal stem cells improves neurological functions after stroke without cell fusion.2009
Author(s)
Xu H, Miki K, Ishibashi S, Inoue J, Sun L, Endo S, Sekiya I, Muneta T, Inazawa J, Dezawa M, Mizusawa H.
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Journal Title
J Neurosci Res. 88
Pages: 3598-3609
Related Report
Peer Reviewed
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