DOI: 10.1002/ame2.70012
Disruption of the blood-brain barrier contributes to neurobehavioral changes observed in rheumatic heart disease
Rukshan Ahamed Mohamed Rafeek1
Riya Thapa1
Samarjeet Saluja1
Bipandeep Banga1
David McMillan2
Kadaba Sri Sriprakash3
Nicholas M.Andronicos1
Adam Hamlin1
Natkunam Ketheesan2
1.School of Science & Technology,University of New England,Armidale,New South Wales,Australia2.School of Science & Technology,University of New England,Armidale,New South Wales,Australia;School of Science,Technology,University of the Sunshine Coast,Sunshine Coast,Queensland,Australia3.School of Science & Technology,University of New England,Armidale,New South Wales,Australia;QIMR Berghofer Medical Research Institute,Brisbane,Queensland,Australia
摘要：Sydenham chorea(SC)is the neurological manifestation associated with acute rheu-matic fever(ARF).ARF and rheumatic heart disease(RHD)are autoimmune complica-tions 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 impli-cated 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 demon-strate neurobehavioral symptoms.However,when the blood-brain barrier(BBB)was disrupted using lipopolysaccharide,all animals that received anti-GAS M protein anti-bodies,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.
机标关键词：barrierheartblood-brainchangescontributesdiseasedisruptionneurobehavioral
论文发表日期：2025-06-30
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：8( 1138-1145 )
英文信息