Estradiol and G1 reduce infarct size and improve immunosuppression after experimental stroke

Bing Zhang, Sandhya Subramanian, Suzan Dziennis, Jia Jia, Masayoshi Uchida, Kozaburo Akiyoshi, Elton Migliati, Anne Lewis, Arthur Vandenbark, Halina Offner, Patricia D. Hurn

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Abstract

Reduced risk and severity of stroke in adult females is thought to depend on normal endogenous levels of estrogen, a well-known neuroprotectant and immunomodulator. In male mice, experimental stroke induces immunosuppression of the peripheral immune system, characterized by a reduction in spleen size and cell numbers and decreased cytokine and chemokine expression. However, stroke-induced immunosuppression has not been evaluated in female mice. To test the hypothesis that estradiol (E2) deficiency exacerbates immunosuppression after focal stroke in females, we evaluated the effect of middle cerebral artery occlusion on infarct size and peripheral and CNS immune responses in ovariectomized mice with or without sustained, controlled levels of 17-β-E2 administered by s.c. implant or the putative membrane estrogen receptor agonist, G1. Both E2- and G1-replacement decreased infarct volume and partially restored splenocyte numbers. Moreover, E2-replacement increased splenocyte proliferation in response to stimulation with anti-CD3/CD28 Abs and normalized aberrant mRNA expression for cytokines, chemokines, and chemokine receptors and percentage of CD4+CD25+FoxP3+ T regulatory cells observed in E2-deficient animals. These beneficial changes in peripheral immunity after E2 replacement were accompanied by a profound reduction in expression of the chemokine, MIP-2, and a 40-fold increased expression of CCR7 in the lesioned brain hemisphere. These results demonstrate for the first time that E2 replacement in ovariectomized female mice improves stroke-induced peripheral immunosuppression.

Original languageEnglish (US)
Pages (from-to)4087-4094
Number of pages8
JournalJournal of Immunology
Volume184
Issue number8
DOIs
StatePublished - Apr 15 2010

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Immunosuppression
Estradiol
Stroke
Chemokines
Estrogens
Chemokine CXCL2
Cytokines
Chemokine Receptors
Middle Cerebral Artery Infarction
Immunologic Factors
Neuroprotective Agents
Regulatory T-Lymphocytes
Immune System
Immunity
Spleen
Cell Count
Messenger RNA
Membranes
Brain

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Zhang, B., Subramanian, S., Dziennis, S., Jia, J., Uchida, M., Akiyoshi, K., ... Hurn, P. D. (2010). Estradiol and G1 reduce infarct size and improve immunosuppression after experimental stroke. Journal of Immunology, 184(8), 4087-4094. https://doi.org/10.4049/jimmunol.0902339

Estradiol and G1 reduce infarct size and improve immunosuppression after experimental stroke. / Zhang, Bing; Subramanian, Sandhya; Dziennis, Suzan; Jia, Jia; Uchida, Masayoshi; Akiyoshi, Kozaburo; Migliati, Elton; Lewis, Anne; Vandenbark, Arthur; Offner, Halina; Hurn, Patricia D.

In: Journal of Immunology, Vol. 184, No. 8, 15.04.2010, p. 4087-4094.

Research output: Contribution to journalArticle

Zhang, B, Subramanian, S, Dziennis, S, Jia, J, Uchida, M, Akiyoshi, K, Migliati, E, Lewis, A, Vandenbark, A, Offner, H & Hurn, PD 2010, 'Estradiol and G1 reduce infarct size and improve immunosuppression after experimental stroke', Journal of Immunology, vol. 184, no. 8, pp. 4087-4094. https://doi.org/10.4049/jimmunol.0902339
Zhang B, Subramanian S, Dziennis S, Jia J, Uchida M, Akiyoshi K et al. Estradiol and G1 reduce infarct size and improve immunosuppression after experimental stroke. Journal of Immunology. 2010 Apr 15;184(8):4087-4094. https://doi.org/10.4049/jimmunol.0902339
Zhang, Bing ; Subramanian, Sandhya ; Dziennis, Suzan ; Jia, Jia ; Uchida, Masayoshi ; Akiyoshi, Kozaburo ; Migliati, Elton ; Lewis, Anne ; Vandenbark, Arthur ; Offner, Halina ; Hurn, Patricia D. / Estradiol and G1 reduce infarct size and improve immunosuppression after experimental stroke. In: Journal of Immunology. 2010 ; Vol. 184, No. 8. pp. 4087-4094.
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