Age-dependent involvement of gut mast cells and histamine in post-stroke inflammation
Abstract Background Risk of stroke-related morbidity and mortality increases significantly with age. Aging is associated with chronic, low-grade inflammation, which is thought to contribute to the poorer outcomes after stroke seen in the elderly. Histamine (HA) is a major molecular mediator of infla...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2020-05-01
|
| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12974-020-01833-1 |
| _version_ | 1819022501943967744 |
|---|---|
| author | Maria Pilar Blasco Anjali Chauhan Pedram Honarpisheh Hilda Ahnstedt John d’Aigle Arunkumar Ganesan Sriram Ayyaswamy Frank Blixt Susan Venable Angela Major David Durgan Anthony Haag Julia Kofler Robert Bryan Louise D. McCullough Bhanu Priya Ganesh |
| author_facet | Maria Pilar Blasco Anjali Chauhan Pedram Honarpisheh Hilda Ahnstedt John d’Aigle Arunkumar Ganesan Sriram Ayyaswamy Frank Blixt Susan Venable Angela Major David Durgan Anthony Haag Julia Kofler Robert Bryan Louise D. McCullough Bhanu Priya Ganesh |
| author_sort | Maria Pilar Blasco |
| collection | DOAJ |
| description | Abstract Background Risk of stroke-related morbidity and mortality increases significantly with age. Aging is associated with chronic, low-grade inflammation, which is thought to contribute to the poorer outcomes after stroke seen in the elderly. Histamine (HA) is a major molecular mediator of inflammation, and mast cells residing in the gut are a primary source of histamine. Methods Stroke was induced in male C57BL/6 J mice at 3 months (young) and 20 months (aged) of age. Role of histamine after stroke was examined using young (Yg) and aged (Ag) mice; mice underwent MCAO surgery and were euthanized at 6 h, 24 h, and 7 days post-ischemia; sham mice received the same surgery but no MCAO. In this work, we evaluated whether worsened outcomes after experimental stroke in aged mice were associated with age-related changes in mast cells, histamine levels, and histamine receptor expression in the gut, brain, and plasma. Results We found increased numbers of mast cells in the gut and the brain with aging. Using the middle cerebral artery occlusion (MCAO) model of ischemic stroke, we demonstrate that stroke leads to increased numbers of gut mast cells and gut histamine receptor expression levels. These gut-centric changes are associated with elevated levels of HA and other pro-inflammatory cytokines including IL-6, G-CSF, TNF-α, and IFN-γ in the peripheral circulation. Our data also shows that post-stroke gut inflammation led to a significant reduction of mucin-producing goblet cells and a loss of gut barrier integrity. Lastly, gut inflammation after stroke is associated with changes in the composition of the gut microbiota as early as 24-h post-stroke. Conclusion An important theme emerging from our results is that acute inflammatory events following ischemic insults in the brain persist longer in the aged mice when compared to younger animals. Taken together, our findings implicate mast cell activation and histamine signaling as a part of peripheral inflammatory response after ischemic stroke, which are profound in aged animals. Interfering with histamine signaling orally might provide translational value to improve stroke outcome. |
| first_indexed | 2024-12-21T04:24:01Z |
| format | Article |
| id | doaj.art-3e5903b6ed724fc293884e494ed85f3e |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-21T04:24:01Z |
| publishDate | 2020-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-3e5903b6ed724fc293884e494ed85f3e2022-12-21T19:16:06ZengBMCJournal of Neuroinflammation1742-20942020-05-0117111610.1186/s12974-020-01833-1Age-dependent involvement of gut mast cells and histamine in post-stroke inflammationMaria Pilar Blasco0Anjali Chauhan1Pedram Honarpisheh2Hilda Ahnstedt3John d’Aigle4Arunkumar Ganesan5Sriram Ayyaswamy6Frank Blixt7Susan Venable8Angela Major9David Durgan10Anthony Haag11Julia Kofler12Robert Bryan13Louise D. McCullough14Bhanu Priya Ganesh15Department of Neurology, University of Texas McGovern Medical SchoolDepartment of Neurology, University of Texas McGovern Medical SchoolDepartment of Neurology, University of Texas McGovern Medical SchoolDepartment of Neurology, University of Texas McGovern Medical SchoolDepartment of Neurology, University of Texas McGovern Medical SchoolDepartment of Anesthesiology, Baylor College of MedicineDepartment of Anesthesiology, Baylor College of MedicineDepartment of Neurology, University of Texas McGovern Medical SchoolDepartment of Pathology and Immunology, Baylor College of MedicineDepartment of Pathology and Immunology, Baylor College of MedicineDepartment of Anesthesiology, Baylor College of MedicineDepartment of Pathology and Immunology, Baylor College of MedicineDepartment of Pathology, University of PittsburgDepartment of Anesthesiology, Baylor College of MedicineDepartment of Neurology, University of Texas McGovern Medical SchoolDepartment of Neurology, University of Texas McGovern Medical SchoolAbstract Background Risk of stroke-related morbidity and mortality increases significantly with age. Aging is associated with chronic, low-grade inflammation, which is thought to contribute to the poorer outcomes after stroke seen in the elderly. Histamine (HA) is a major molecular mediator of inflammation, and mast cells residing in the gut are a primary source of histamine. Methods Stroke was induced in male C57BL/6 J mice at 3 months (young) and 20 months (aged) of age. Role of histamine after stroke was examined using young (Yg) and aged (Ag) mice; mice underwent MCAO surgery and were euthanized at 6 h, 24 h, and 7 days post-ischemia; sham mice received the same surgery but no MCAO. In this work, we evaluated whether worsened outcomes after experimental stroke in aged mice were associated with age-related changes in mast cells, histamine levels, and histamine receptor expression in the gut, brain, and plasma. Results We found increased numbers of mast cells in the gut and the brain with aging. Using the middle cerebral artery occlusion (MCAO) model of ischemic stroke, we demonstrate that stroke leads to increased numbers of gut mast cells and gut histamine receptor expression levels. These gut-centric changes are associated with elevated levels of HA and other pro-inflammatory cytokines including IL-6, G-CSF, TNF-α, and IFN-γ in the peripheral circulation. Our data also shows that post-stroke gut inflammation led to a significant reduction of mucin-producing goblet cells and a loss of gut barrier integrity. Lastly, gut inflammation after stroke is associated with changes in the composition of the gut microbiota as early as 24-h post-stroke. Conclusion An important theme emerging from our results is that acute inflammatory events following ischemic insults in the brain persist longer in the aged mice when compared to younger animals. Taken together, our findings implicate mast cell activation and histamine signaling as a part of peripheral inflammatory response after ischemic stroke, which are profound in aged animals. Interfering with histamine signaling orally might provide translational value to improve stroke outcome.http://link.springer.com/article/10.1186/s12974-020-01833-1Mast cellsHistamineHistamine receptorCytokinesPost-strokeMicrobiome |
| spellingShingle | Maria Pilar Blasco Anjali Chauhan Pedram Honarpisheh Hilda Ahnstedt John d’Aigle Arunkumar Ganesan Sriram Ayyaswamy Frank Blixt Susan Venable Angela Major David Durgan Anthony Haag Julia Kofler Robert Bryan Louise D. McCullough Bhanu Priya Ganesh Age-dependent involvement of gut mast cells and histamine in post-stroke inflammation Journal of Neuroinflammation Mast cells Histamine Histamine receptor Cytokines Post-stroke Microbiome |
| title | Age-dependent involvement of gut mast cells and histamine in post-stroke inflammation |
| title_full | Age-dependent involvement of gut mast cells and histamine in post-stroke inflammation |
| title_fullStr | Age-dependent involvement of gut mast cells and histamine in post-stroke inflammation |
| title_full_unstemmed | Age-dependent involvement of gut mast cells and histamine in post-stroke inflammation |
| title_short | Age-dependent involvement of gut mast cells and histamine in post-stroke inflammation |
| title_sort | age dependent involvement of gut mast cells and histamine in post stroke inflammation |
| topic | Mast cells Histamine Histamine receptor Cytokines Post-stroke Microbiome |
| url | http://link.springer.com/article/10.1186/s12974-020-01833-1 |
| work_keys_str_mv | AT mariapilarblasco agedependentinvolvementofgutmastcellsandhistamineinpoststrokeinflammation AT anjalichauhan agedependentinvolvementofgutmastcellsandhistamineinpoststrokeinflammation AT pedramhonarpisheh agedependentinvolvementofgutmastcellsandhistamineinpoststrokeinflammation AT hildaahnstedt agedependentinvolvementofgutmastcellsandhistamineinpoststrokeinflammation AT johndaigle agedependentinvolvementofgutmastcellsandhistamineinpoststrokeinflammation AT arunkumarganesan agedependentinvolvementofgutmastcellsandhistamineinpoststrokeinflammation AT sriramayyaswamy agedependentinvolvementofgutmastcellsandhistamineinpoststrokeinflammation AT frankblixt agedependentinvolvementofgutmastcellsandhistamineinpoststrokeinflammation AT susanvenable agedependentinvolvementofgutmastcellsandhistamineinpoststrokeinflammation AT angelamajor agedependentinvolvementofgutmastcellsandhistamineinpoststrokeinflammation AT daviddurgan agedependentinvolvementofgutmastcellsandhistamineinpoststrokeinflammation AT anthonyhaag agedependentinvolvementofgutmastcellsandhistamineinpoststrokeinflammation AT juliakofler agedependentinvolvementofgutmastcellsandhistamineinpoststrokeinflammation AT robertbryan agedependentinvolvementofgutmastcellsandhistamineinpoststrokeinflammation AT louisedmccullough agedependentinvolvementofgutmastcellsandhistamineinpoststrokeinflammation AT bhanupriyaganesh agedependentinvolvementofgutmastcellsandhistamineinpoststrokeinflammation |