T- and B-cell-deficient mice with experimental stroke have reduced lesion size and inflammation

Patricia D. Hurn, Sandhya Subramanian, Susan M. Parker, Michael E. Afentoulis, Laurie J. Kaler, Arthur A. Vandenbark, Halina Offner

Research output: Contribution to journalArticle

257 Scopus citations

Abstract

Stroke induction in immunologically competent mice not only produces local ischemia and brain damage, but also induces early inflammatory changes in brain and peripheral immune responses. Although immune elements clearly are activated after brain vascular occlusion, the relative contribution of T and B lymphocytes to the developing lesion has not been quantified. We evaluated effects 22 h after middle cerebral artery occlusion (90 mins) on histologic injury and peripheral immune activation in severe combined immunodeficient (SCID) mice lacking T and B cells. Cortical and total infarct volumes were strikingly reduced in male SCID mice (n=14, 33±4% of contralateral cortex, n=10, 52±3% of contralateral hemisphere) versus immunologically intact C57BL/6 mice (wild type, n=9, 57±5% of contralateral cortex, 57±4% of contralateral hemisphere) (P<0.01). Striatal infarction was not altered (77±7% of contralateral striatum in SCID, 84±7% in wild type), suggesting that the core of the evolving ischemic lesion was not impacted by lack of T and B cells. As expected, inflammatory factors from immune cells in ischemic SCID brains were essentially absent, with the exception of interleukin-1β increase in both SCID and wild type tissue. Spleen cell numbers were low in SCID mice, but were further reduced 22 h after stroke, with substantial reduction in most inflammatory factors except for increased expression of interferon-γ and macrophage inflammatory protein (MIP)-2. These data quantify the damaging effect of T and B lymphocytes on early, evolving ischemic brain injury, and further implicate interleukin-1β in brain and interferon-γ and MIP-2 in spleen as inflammatory factors produced by cells other than T and B cells.

Original languageEnglish (US)
Pages (from-to)1798-1805
Number of pages8
JournalJournal of Cerebral Blood Flow and Metabolism
Volume27
Issue number11
DOIs
StatePublished - Nov 2007

Keywords

  • Cerebral ischemia
  • Chemokines
  • Cytokines
  • Spleen
  • T/B-deficient mice

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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