PMID- 27600707 OWN - NLM STAT- MEDLINE DCOM- 20171025 LR - 20181113 IS - 2051-5960 (Electronic) IS - 2051-5960 (Linking) VI - 4 IP - 1 DP - 2016 Sep 6 TI - Multiplex immunoassay characterization and species comparison of inflammation in acute and non-acute ischemic infarcts in human and mouse brain tissue. PG - 100 LID - 10.1186/s40478-016-0371-y [doi] LID - 100 AB - This study provides a parallel characterization of the cytokine and chemokine response to stroke in the human and mouse brain at different stages of infarct resolution. The study goal was to address the hypothesis that chronic inflammation may contribute to stroke-related dementia. We used C57BL/6 and BALB/c mice to control for strain related differences in the mouse immune response. Our data indicate that in both mouse strains, and humans, there is increased granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin-6 (IL-6), interleukin-12 p70 (IL-12p70), interferon gamma-induced protein-10 (IP-10), keratinocyte chemoattractant/interleukin-8 (KC/IL-8), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha), macrophage inflammatory protein-1beta (MIP-1beta), regulated on activation, normal T cell expressed and secreted (RANTES), and Tumor necrosis factor-alpha (TNF-alpha) in the infarct core during the acute time period. Nevertheless, correlation and two-way ANOVA analyses reveal that despite this substantial overlap between species, there are still significant differences, particularly in the regulation of granulocyte colony-stimulating factor (G-CSF), which is increased in mice but not in humans. In the weeks after stroke, during the stage of liquefactive necrosis, there is significant resolution of the inflammatory response to stroke within the infarct. However, CD68+ macrophages remain present, and levels of IL-6 and MCP-1 remain chronically elevated in infarcts from both mice and humans. Furthermore, there is a chronic T cell response within the infarct in both species. This response is differentially polarized towards a T helper 1 (Th1) response in C57BL/6 mice, and a T helper 2 (Th2) response in BALB/c mice, suggesting that the chronic inflammatory response to stroke may follow a different trajectory in different patients. To control for the fact that the average age of the patients used in this study was 80 years, they were of both sexes, and many had suffered from multiple strokes, we also present findings that reveal how the chronic inflammatory response to stroke is impacted by age, sex, and multiple strokes in mice. Our data indicate that the chronic cytokine and chemokine response to stroke is not substantially altered in 18-month old compared to 3-month old C57BL/6 mice, although T cell infiltration is attenuated. We found a significant correlation in the chronic cytokine response to stroke in males and females. However, the chronic cytokine response to stroke was mildly exacerbated by a recurrent stroke in both C57BL/6 and BALB/c mice. FAU - Nguyen, Thuy-Vi V AU - Nguyen TV AD - Department of Immunobiology, University of Arizona College of Medicine, Tucson, AZ, USA. AD - Department of Neurology, University of Arizona College of Medicine, Tucson, AZ, USA. FAU - Frye, Jennifer B AU - Frye JB AD - Department of Immunobiology, University of Arizona College of Medicine, Tucson, AZ, USA. FAU - Zbesko, Jacob C AU - Zbesko JC AD - Department of Immunobiology, University of Arizona College of Medicine, Tucson, AZ, USA. FAU - Stepanovic, Kristina AU - Stepanovic K AD - Department of Immunobiology, University of Arizona College of Medicine, Tucson, AZ, USA. FAU - Hayes, Megan AU - Hayes M AD - Department of Immunobiology, University of Arizona College of Medicine, Tucson, AZ, USA. FAU - Urzua, Alex AU - Urzua A AD - Department of Immunobiology, University of Arizona College of Medicine, Tucson, AZ, USA. FAU - Serrano, Geidy AU - Serrano G AD - Banner Sun Health Research Institute, Sun City, AZ, USA. FAU - Beach, Thomas G AU - Beach TG AD - Banner Sun Health Research Institute, Sun City, AZ, USA. FAU - Doyle, Kristian P AU - Doyle KP AD - Department of Immunobiology, University of Arizona College of Medicine, Tucson, AZ, USA. doylekr@email.arizona.edu. AD - Department of Neurology, University of Arizona College of Medicine, Tucson, AZ, USA. doylekr@email.arizona.edu. AD - Arizona Center on Aging, University of Arizona College of Medicine, Tucson, AZ, USA. doylekr@email.arizona.edu. LA - eng GR - K99 NR013593/NR/NINR NIH HHS/United States GR - P30 AG019610/AG/NIA NIH HHS/United States GR - R00 NR013593/NR/NINR NIH HHS/United States GR - U24 NS072026/NS/NINDS NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20160906 PL - England TA - Acta Neuropathol Commun JT - Acta neuropathologica communications JID - 101610673 SB - IM EIN - Acta Neuropathol Commun. 2016;4(1):104. PMID: 27669748 MH - Acute Disease MH - Aged MH - Aged, 80 and over MH - Aging/metabolism/pathology MH - Animals MH - Brain/*immunology/pathology MH - Brain Infarction/*immunology/pathology MH - Chronic Disease MH - Female MH - Humans MH - Immunoassay MH - Immunohistochemistry MH - Infarction, Middle Cerebral Artery MH - Male MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Middle Aged MH - Recurrence MH - Sex Characteristics MH - Species Specificity PMC - PMC5011964 OTO - NOTNLM OT - Chronic infarcts OT - Cytokines OT - Inflammation OT - Liquefactive necrosis OT - Stroke EDAT- 2016/09/08 06:00 MHDA- 2017/10/27 06:00 PMCR- 2016/09/06 CRDT- 2016/09/08 06:00 PHST- 2016/07/13 00:00 [received] PHST- 2016/08/19 00:00 [accepted] PHST- 2016/09/08 06:00 [entrez] PHST- 2016/09/08 06:00 [pubmed] PHST- 2017/10/27 06:00 [medline] PHST- 2016/09/06 00:00 [pmc-release] AID - 10.1186/s40478-016-0371-y [pii] AID - 371 [pii] AID - 10.1186/s40478-016-0371-y [doi] PST - epublish SO - Acta Neuropathol Commun. 2016 Sep 6;4(1):100. doi: 10.1186/s40478-016-0371-y.