Differential affection of intestinal immune cell populations after cerebral ischemia in mice.
ABSTRACT Infections cause a major clinical problem within the first days after cerebral stroke. In a mouse model we have recently demonstrated that stroke leads to immunodepression facilitating spontaneous bacterial pneumonia and bacteremia. So far, it has been unknown whether poststroke immunomodulation impairs local intestinal immune populations which may promote gut barrier dysfunction leading to translocation of intestinal microorganisms and microbial products. In this study, we investigated changes in intestinal intraepithelial, lamina propria and Peyer's patch immune cell populations after experimental stroke.
129SV mice were subjected to experimental stroke by filament occlusion of the middle cerebral artery or sham operation. After 24 h, animals were sacrificed, and intraepithelial lymphocytes, lamina propria lymphocytes and Peyer's patches were isolated and leukocyte subpopulations analyzed by flow cytometry.
Peyer's patches revealed a significant reduction of T and B cell counts after cerebral ischemia, while no differences in natural killer cells and macrophages were observed. In contrast, no significant changes in intraepithelial and lamina propria lymphocyte subsets were observed in middle cerebral artery animals compared to controls.
Cerebral ischemia has differential effects on cellularity of gut-associated lymphoid tissue. Further studies on the mechanisms involved in quantitative changes of gut immune cells as well as on the function of these cells are needed to better understand the consequences of stroke-induced alterations of the local intestinal immune compartment for the enhanced susceptibility to infections after stroke.
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ABSTRACT: Neurological disorders affect over one billion lives each year worldwide. With population aging, this number is on the rise, making neurological disorders a major public health concern. Within this category, stroke represents the second leading cause of death, ranking after heart disease, and is associated with long-term physical disabilities and impaired quality of life. In this review, we will focus our attention on examining the tight crosstalk between brain and immune system and how disruption of this mutual interaction is at the basis of stroke pathophysiology. We will also explore the emerging literature in support of the use of immuno-modulatory molecules as potential therapeutic interventions in stroke.Molecular and Cellular Neuroscience 08/2012; · 3.84 Impact Factor
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ABSTRACT: Stroke-induced immunodepression (SIID) results when T cell and non-T immune cells, such as B cells, NK cells and monocytes, are reduced in the peripheral blood and spleen after stroke. We investigated the hypothesis that T cells are required for the reductions in non-T cell subsets observed in SIID, and further examined a potential correlation between lymphopenia and High-mobility group protein B1 (HMGB1) release, a protein that regulates inflammation and immunodepression. Our results showed that focal ischemia resulted in similar cortical infarct sizes in both wild type (WT) Sprague Dawley (SD) rats and nude rats with a SD genetic background, which excludes the possibility of different infarct sizes affecting SIID. In addition, the numbers of CD68-positive macrophages in the ischemic brain did not differ between WT and nude rats. Numbers of total peripheral blood mononuclear cells (PBMCs) or splenocytes and lymphocyte subsets, including T cells, CD4(+) or CD8(+) T cells, B cells and monocytes in the blood and spleen, were decreased after stroke in WT rats. In nude rats, however, the total number of PBMCs and absolute numbers of NK cells, B cells and monocytes were increased in the peripheral blood after stroke; nude rats are athymic therefore they have few T cells present. Adoptive transfer of WT splenocytes into nude rats before stroke resulted in lymphopenia after stroke similar to WT rats. Moreover, in vitro T cell proliferation stimulated by Concanavalin A was significantly inhibited in WT rats as well as in nude rats receiving WT splenocyte adoptive transfer, suggesting that T cell function is indeed inhibited after stroke. Lastly, we demonstrated that stroke-induced lymphopenia is associated with a reduction in HMGB1 release in the peripheral blood. In conclusion, T cells are required for stroke-induced reductions in non-T immune cells and they are the most crucial lymphocytes for SIID.PLoS ONE 01/2013; 8(3):e59602. · 3.53 Impact Factor
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ABSTRACT: The idea that the brain is immunologically privileged and displays an atypical leukocyte recruitment profile following injury has influenced our ideas about how signals might be carried between brain and the periphery. For many, this has encouraged a cerebrocentric view of immunological responses to CNS injury, with little reference to the potential contribution from other organs. However, it is clear that bidirectional pathways between the brain and the peripheral immune system are important in the pathogenesis of CNS disease. In recent years, we have begun to understand the signals that are carried to the periphery and discovered new functions for known chemokines, made by the liver in response to brain injury, as important regulators of the CNS inflammatory response.Brain Behavior and Immunity 11/2011; 26(4):534-40. · 5.61 Impact Factor