Group A streptococcal antigen exposed rat model to investigate neurobehavioral and cardiac complications associated with post-streptococcal autoimmune sequelae  

作　　者：Rukshan A.M.Rafeek Catherine M.Lobbe Ethan C.Wilkinson Adam S.Hamlin Nicholas M.Andronicos David J.McMillan Kadaba S.Sriprakash Natkunam Ketheesan 

机构地区：[1]School of Science&Technology,University of New England,Armidale,NSW,Australia [2]School of Science,Technology,Engineering and Genecology Research Centre,University of the Sunshine Coast,Maroochydore DC,QLD,Australia [3]QIMR Berghofer Medical Research Institute,Herston,QLD,Australia

出　　处：《Animal Models and Experimental Medicine》2021年第2期151-161,共11页动物模型与实验医学（英文）

基　　金：RAM Rafeek is recipient of International Postgraduate Research Award(IPRA)from University of New England.CM Lobbe and E.Wilkinson are recipients of student scholarship from the Royal College of Pathologists of Australasia(RCPA).

摘　　要：Background:The neuropsychiatric disorders due to post-streptococcal autoimmune complications such as Sydenham's chorea(SC)are associated with acute rheumatic fever and rheumatic heart disease(ARF/RHD).An animal model that exhibits char-acteristics of both cardiac and neurobehavioral defects in ARF/RHD would be an important adjunct for future studies.Since age,gender,strain differences,and geno-types impact on the development of autoimmunity,we investigated the behavior of male and female Wistar and Lewis rat strains in two age cohorts(6 weeks and 12 weeks)under normal husbandry conditions and following exposure to group A streptococcus(GAS).Methods:Standard behavioral assessments were performed to determine the impair-ments in fine motor control(food manipulation test),gait and balance(beam walk-ing test),and obsessive-compulsive behavior(grooming and marble burying tests).Furthermore,electrocardiography,histology,and behavioral assessments were per-formed on male and female Lewis rats injected with GAS antigens.Results:For control Lewis rats there were no significant age and gender dependent differences in marble burying,food manipulation,beam walking and grooming be-haviors.In contrast significant age-dependent differences were observed in Wistar rats in all the behavioral tests except for food manipulation.Therefore,Lewis rats were selected for further experiments to determine the effect of GAS.After ex-posure to GAS,Lewis rats demonstrated neurobehavioral abnormalities and cardiac pathology akin to SC and ARF/RHD,respectively.Conclusion:We have characterised a new model that provides longitudinal stability of age-dependent behavior,to simultaneously investigate both neurobehavioral and cardiac abnormalities associated with post-streptococcal complications.

关 键 词：animal model group A streptococcus Lewis rats paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections(PANDAS) rheumatic fever rheumatic heart disease sydenham chorea(SC) 

分 类 号：R515[医药卫生—内科学] R-332[医药卫生—临床医学]