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PMID: 19107136 Published · ppublish English Journal Article Research Support, N.I.H., Intramural

Mucosal tolerance to E-selectin promotes the survival of newly generated neuroblasts via regulatory T-cell induction after stroke in spontaneously hypertensive rats.

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism ·Vol. 29 ·No. 3 ·2009-03-00 ·Pages 606-20

Ishibashi S, Maric D, Mou Y, Ohtani R, Ruetzler C, Hallenbeck JM

Abstract

Neuroblasts in the subventricular zone (SVZ) proliferate markedly after brain ischemia, and migrate to the site of injury along with blood vessels. However, a large fraction of stroke-generated neuroblasts die shortly after being born, in part, because of local inflammation. In spontaneously hypertensive rats (SHRs) subjected to permanent middle cerebral artery occlusion, we primed E-selectin-specific regulatory T cells (Tregs) by repetitive intranasal administration of recombinant E-selectin to target local secretion of immunomodulating, antiinflammatory cytokines to activating blood vessel segments. E-selectin-tolerized SHRs had decreased infarction volumes, and increased numbers of Tregs in the cervical lymph nodes and ischemic brain. The brain Tregs were distributed primarily in periinfarct regions. E-selectin tolerization did not alter cellular proliferation in the ipsilateral SVZ after stroke, but the expression of tumor necrosis factor on vascular niche blood vessels was suppressed and both doublecortin protein levels and the number of newly generated neuroblasts or neurons were increased in the brain. This enhanced survival of neural progenitor cells and neurons was paralleled by improved functional performance. These studies suggest that E-selectin-specific Tregs can modulate the efficacy of neurogenesis after ischemia and promote repair after brain injury.

MeSH Terms
Administration, Intranasal Animals Cell Death Cytokines/biosynthesis,immunology Disease Models, Animal Doublecortin Protein E-Selectin/administration & dosage,immunology Immune Tolerance Immunity, Mucosal/immunology Infarction, Middle Cerebral Artery/complications,immunology Nasal Mucosa/immunology Neurons/immunology,pathology Rats Rats, Inbred SHR Recombinant Proteins/administration & dosage,immunology Stem Cells/immunology,pathology Stroke/immunology,pathology,prevention & control T-Lymphocytes/immunology
Chemicals
Cytokines Dcx protein, rat Doublecortin Protein E-Selectin Recombinant Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Ishibashi Satoru
Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health (NIH), Bethesda, Maryland 20892-4476, USA.
Maric Dragan
Mou Yongshan
Ohtani Ryo
Ruetzler Christl
Hallenbeck John M
References (40)
40 references, click to expand
  1. Antigen-driven bystander suppression after oral administration of antigens.
    J Exp Med. 1991 Oct 1;174(4):791-8 PMID: 1717632
  2. Control of regulatory T cell development by the transcription factor Foxp3.
    Science. 2003 Feb 14;299(5609):1057-61 PMID: 12522256
  3. The mucosal milieu creates tolerogenic dendritic cells and T(R)1 and T(H)3 regulatory cells.
    Nat Immunol. 2001 Aug;2(8):671-2 PMID: 11477400
  4. Adhesion molecules in cerebrovascular diseases. Evidence for an inflammatory endothelial activation in cerebral large- and small-vessel disease.
    Stroke. 1999 Aug;30(8):1647-50 PMID: 10436116
  5. Endothelial-leukocyte adhesion molecules.
    Annu Rev Immunol. 1993;11:767-804 PMID: 8476577
  6. Long-term neuroblast migration along blood vessels in an area with transient angiogenesis and increased vascularization after stroke.
    Stroke. 2007 Nov;38(11):3032-9 PMID: 17901386
  7. Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis.
    Science. 1994 Aug 26;265(5176):1237-40 PMID: 7520605
  8. Neuroprotection by IL-10-producing MOG CD4+ T cells following ischemic stroke.
    J Neurol Sci. 2005 Jun 15;233(1-2):125-32 PMID: 15894335
  9. Mucosal tolerization to E-selectin protects against memory dysfunction and white matter damage in a vascular cognitive impairment model.
    J Cereb Blood Flow Metab. 2008 Feb;28(2):341-53 PMID: 17637705
  10. CD4+CD25+ T regulatory cells control anti-islet CD8+ T cells through TGF-beta-TGF-beta receptor interactions in type 1 diabetes.
    Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10878-83 PMID: 12949259
  11. Subventricular zone-derived neuroblasts migrate and differentiate into mature neurons in the post-stroke adult striatum.
    J Neurosci. 2006 Jun 14;26(24):6627-36 PMID: 16775151
  12. Suppression of stroke-induced progenitor proliferation in adult subventricular zone by tumor necrosis factor receptor 1.
    J Cereb Blood Flow Metab. 2008 Sep;28(9):1574-87 PMID: 18493257
  13. Tumor necrosis factor-alpha and interleukin-18 modulate neuronal cell fate in embryonic neural progenitor culture.
    Brain Res. 2005 Aug 30;1054(2):152-8 PMID: 16054598
  14. Induction of mucosal tolerance to E-selectin targets immunomodulation to activating vessel segments and prevents ischemic and hemorrhagic stroke.
    Ernst Schering Res Found Workshop. 2004;(47):117-32 PMID: 15032057
  15. Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors.
    Cell. 2002 Aug 23;110(4):429-41 PMID: 12202033
  16. Mucosal tolerance to E-selectin provides cell-mediated protection against ischemic brain injury.
    Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15107-12 PMID: 14645708
  17. Neurogenesis in dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat.
    Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4710-5 PMID: 11296300
  18. The many faces of tumor necrosis factor in stroke.
    Nat Med. 2002 Dec;8(12):1363-8 PMID: 12457181
  19. The olfactory route for cerebrospinal fluid drainage into the peripheral lymphatic system.
    Neuropathol Appl Neurobiol. 2006 Aug;32(4):388-96 PMID: 16866984
  20. Proliferating subventricular zone cells in the adult mammalian forebrain can differentiate into neurons and glia.
    Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):2074-7 PMID: 8446631
  21. Tactile extinction: distinguishing between sensorimotor and motor asymmetries in rats with unilateral nigrostriatal damage.
    Pharmacol Biochem Behav. 1982 Mar;16(3):455-62 PMID: 7079281
  22. Neurogenesis in rats after focal cerebral ischemia is enhanced by indomethacin.
    Stroke. 2005 Dec;36(12):2718-24 PMID: 16282546
  23. Intranasal administration of E-selectin to induce immunological tolerization can suppress subarachnoid hemorrhage-induced vasospasm implicating immune and inflammatory mechanisms in its genesis.
    Brain Res. 2007 Feb 9;1132(1):177-84 PMID: 17188657
  24. Elevated body swing test: a new behavioral parameter for rats with 6-hydroxydopamine-induced hemiparkinsonism.
    J Neurosci. 1995 Jul;15(7 Pt 2):5372-8 PMID: 7623159
  25. Electrophysiological neurodifferentiation of subventricular zone-derived precursor cells following stroke.
    Neurosci Lett. 2008 Sep 19;442(3):305-8 PMID: 18647640
  26. Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins.
    Science. 1989 Mar 3;243(4895):1160-5 PMID: 2466335
  27. Neuroprotective properties of cultured neural progenitor cells are associated with the production of sonic hedgehog.
    Neuroscience. 2005;131(4):899-916 PMID: 15749344
  28. Intranasally induced immunological tolerance is determined by characteristics of the draining lymph nodes: studies with OVA and human cartilage gp-39.
    J Immunol. 1999 Feb 15;162(4):1994-8 PMID: 9973470
  29. Induction of immunologic tolerance to myelin basic protein prevents central nervous system autoimmunity and improves outcome after stroke.
    Stroke. 2008 May;39(5):1575-82 PMID: 18323496
  30. Proliferating progenitor cells: a required cellular element for induction of ischemic tolerance in the brain.
    J Cereb Blood Flow Metab. 2008 Jun;28(6):1104-13 PMID: 18319730
  31. Stroke risk factors prepare rat brainstem tissues for modified local Shwartzman reaction.
    Stroke. 1988 Jul;19(7):863-9 PMID: 3388457
  32. For the long run: maintaining germinal niches in the adult brain.
    Neuron. 2004 Mar 4;41(5):683-6 PMID: 15003168
  33. Clinical pharmacological issues in the development of acute stroke therapies.
    Br J Pharmacol. 2008 Mar;153 Suppl 1:S112-9 PMID: 18311155
  34. Neuronal replacement from endogenous precursors in the adult brain after stroke.
    Nat Med. 2002 Sep;8(9):963-70 PMID: 12161747
  35. Human CD4(+)CD25(+) cells: a naturally occurring population of regulatory T cells.
    Blood. 2001 Nov 1;98(9):2736-44 PMID: 11675346
  36. Role of central nervous system microvascular pericytes in activation of antigen-primed splenic T-lymphocytes.
    J Neurosci Res. 1999 Mar 1;55(5):578-87 PMID: 10082080
  37. Cytokines regulate vascular functions related to stability of the atherosclerotic plaque.
    J Cardiovasc Pharmacol. 1995;25 Suppl 2:S9-12 PMID: 8699871
  38. Tumor necrosis factor receptor 1 is a negative regulator of progenitor proliferation in adult hippocampal neurogenesis.
    J Neurosci. 2006 Sep 20;26(38):9703-12 PMID: 16988041
  39. Chronic treatment with minocycline preserves adult new neurons and reduces functional impairment after focal cerebral ischemia.
    Stroke. 2007 Jan;38(1):146-52 PMID: 17122429
  40. A neurovascular niche for neurogenesis after stroke.
    J Neurosci. 2006 Dec 13;26(50):13007-16 PMID: 17167090
Article Info
Journal
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
Abbr.
J Cereb Blood Flow Metab
ISSN
1559-7016
DOI
10.1038/jcbfm.2008.153
Published
2009-03-00
Epub
2008-00-24
Pages
606-20
Language
English
Region
United States
NLM ID
8112566
PMCID
PMC2692388
Subset
IM
Grants
Intramural NIH HHS · Z01 NS002924-12 · United States
External Links
PubMed source DOI: 10.1038/jcbfm.2008.153 PMC Full Text View journal details
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