Disruption of the blood–brain barrier contributes to neurobehavioral changes observed in rheumatic heart disease
Abstract Sydenham chorea (SC) is the neurological manifestation associated with acute rheumatic fever (ARF). ARF and rheumatic heart disease (RHD) are autoimmune complications triggered by a group A streptococcal (GAS) infection. In ARF/RHD and SC, tissue cross‐reactive antibodies and T‐cells genera...
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Wiley
2025-06-01
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| Series: | Animal Models and Experimental Medicine |
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| Online Access: | https://doi.org/10.1002/ame2.70012 |
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| author | Rukshan Ahamed Mohamed Rafeek Riya Thapa Samarjeet Saluja Bipandeep Banga David McMillan Kadaba Sri Sriprakash Nicholas M. Andronicos Adam Hamlin Natkunam Ketheesan |
| author_facet | Rukshan Ahamed Mohamed Rafeek Riya Thapa Samarjeet Saluja Bipandeep Banga David McMillan Kadaba Sri Sriprakash Nicholas M. Andronicos Adam Hamlin Natkunam Ketheesan |
| author_sort | Rukshan Ahamed Mohamed Rafeek |
| collection | DOAJ |
| description | Abstract Sydenham chorea (SC) is the neurological manifestation associated with acute rheumatic fever (ARF). ARF and rheumatic heart disease (RHD) are autoimmune complications triggered by a group A streptococcal (GAS) infection. In ARF/RHD and SC, tissue cross‐reactive antibodies and T‐cells generated against GAS antigens have been implicated in the pathogenesis. In SC, antibodies against GAS antigens are known to cross‐react with neuronal proteins causing neurological manifestations including choreiform movements and neuropsychiatric symptoms such as irritability, attention deficit, and obsessive‐compulsive disorder. Previous studies in a rat autoimmune valvulitis (RAV) model of RHD, have shown that injection of streptococcal M protein could cause both cardiac and neurological symptoms. In this study it was shown that adoptive transfer of serum with anti‐GAS M antibodies to naive rats caused carditis but failed to demonstrate neurobehavioral symptoms. However, when the blood–brain barrier (BBB) was disrupted using lipopolysaccharide, all animals that received anti‐GAS M protein antibodies, developed neurobehavioral defects in addition to carditis. This highlights that impaired BBB integrity is essential for the development of neurobehavioral symptoms. The use of the RAV model and the disruption of BBB required for the development of neurobehavioral changes provides a platform to further investigate the mechanisms that lead to antibodies binding to basal ganglia structures that cause SC. |
| format | Article |
| id | doaj-art-7ce77437fbd541cdbb922b2d2d5efb7e |
| institution | OA Journals |
| issn | 2576-2095 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
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| series | Animal Models and Experimental Medicine |
| spelling | doaj-art-7ce77437fbd541cdbb922b2d2d5efb7e2025-08-20T02:35:19ZengWileyAnimal Models and Experimental Medicine2576-20952025-06-01861138114510.1002/ame2.70012Disruption of the blood–brain barrier contributes to neurobehavioral changes observed in rheumatic heart diseaseRukshan Ahamed Mohamed Rafeek0Riya Thapa1Samarjeet Saluja2Bipandeep Banga3David McMillan4Kadaba Sri Sriprakash5Nicholas M. Andronicos6Adam Hamlin7Natkunam Ketheesan8School of Science & Technology University of New England Armidale New South Wales AustraliaSchool of Science & Technology University of New England Armidale New South Wales AustraliaSchool of Science & Technology University of New England Armidale New South Wales AustraliaSchool of Science & Technology University of New England Armidale New South Wales AustraliaSchool of Science & Technology University of New England Armidale New South Wales AustraliaSchool of Science & Technology University of New England Armidale New South Wales AustraliaSchool of Science & Technology University of New England Armidale New South Wales AustraliaSchool of Science & Technology University of New England Armidale New South Wales AustraliaSchool of Science & Technology University of New England Armidale New South Wales AustraliaAbstract Sydenham chorea (SC) is the neurological manifestation associated with acute rheumatic fever (ARF). ARF and rheumatic heart disease (RHD) are autoimmune complications triggered by a group A streptococcal (GAS) infection. In ARF/RHD and SC, tissue cross‐reactive antibodies and T‐cells generated against GAS antigens have been implicated in the pathogenesis. In SC, antibodies against GAS antigens are known to cross‐react with neuronal proteins causing neurological manifestations including choreiform movements and neuropsychiatric symptoms such as irritability, attention deficit, and obsessive‐compulsive disorder. Previous studies in a rat autoimmune valvulitis (RAV) model of RHD, have shown that injection of streptococcal M protein could cause both cardiac and neurological symptoms. In this study it was shown that adoptive transfer of serum with anti‐GAS M antibodies to naive rats caused carditis but failed to demonstrate neurobehavioral symptoms. However, when the blood–brain barrier (BBB) was disrupted using lipopolysaccharide, all animals that received anti‐GAS M protein antibodies, developed neurobehavioral defects in addition to carditis. This highlights that impaired BBB integrity is essential for the development of neurobehavioral symptoms. The use of the RAV model and the disruption of BBB required for the development of neurobehavioral changes provides a platform to further investigate the mechanisms that lead to antibodies binding to basal ganglia structures that cause SC.https://doi.org/10.1002/ame2.70012animal modelblood–brain‐barriergroup a streptococcusrheumatic feverSydenham's chorea |
| spellingShingle | Rukshan Ahamed Mohamed Rafeek Riya Thapa Samarjeet Saluja Bipandeep Banga David McMillan Kadaba Sri Sriprakash Nicholas M. Andronicos Adam Hamlin Natkunam Ketheesan Disruption of the blood–brain barrier contributes to neurobehavioral changes observed in rheumatic heart disease Animal Models and Experimental Medicine animal model blood–brain‐barrier group a streptococcus rheumatic fever Sydenham's chorea |
| title | Disruption of the blood–brain barrier contributes to neurobehavioral changes observed in rheumatic heart disease |
| title_full | Disruption of the blood–brain barrier contributes to neurobehavioral changes observed in rheumatic heart disease |
| title_fullStr | Disruption of the blood–brain barrier contributes to neurobehavioral changes observed in rheumatic heart disease |
| title_full_unstemmed | Disruption of the blood–brain barrier contributes to neurobehavioral changes observed in rheumatic heart disease |
| title_short | Disruption of the blood–brain barrier contributes to neurobehavioral changes observed in rheumatic heart disease |
| title_sort | disruption of the blood brain barrier contributes to neurobehavioral changes observed in rheumatic heart disease |
| topic | animal model blood–brain‐barrier group a streptococcus rheumatic fever Sydenham's chorea |
| url | https://doi.org/10.1002/ame2.70012 |
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