Open AccessT- and B-Cell-Deficient Mice with Experimental Stroke have Reduced Lesion Size and Inflammation
Author(s) -
Patricia D. Hurn,
Sarah Subramanian,
Susan Parker,
Michael Afentoulis,
Laurie J. Kaler,
Arthur A. Vandenbark,
Halina Offner
Publication year - 2007
Publication title -
journal of cerebral blood flow and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.167
H-Index - 193
eISSN - 1559-7016
pISSN - 0271-678X
DOI - 10.1038/sj.jcbfm.9600482
Subject(s) - lesion , inflammation , immune system , cortex (anatomy) , medicine , pathology , ischemia , cerebral cortex , spleen , stroke (engine) , brain ischemia , brain damage , middle cerebral artery , immunology , biology , endocrinology , neuroscience , mechanical engineering , engineering
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.