Influence of sex on mortality and pathology of urinary/respiratory system in EAE model of Lewis rat

Introduction:Multiple sclerosis (MS) is a demyelinating chronic inflammatory disease of the centralnervous system. Experimental autoimmune encephalomyelitis (EAE) is a widely used modelfor MS based on autoimmune, histopathological, and clinical similarities. Pathological effecton urinary system and lung during MS has been reported. On the other hand, it is known thatMS affects women more than men and this has been attributed to sex hormones, and/or sexlinkedgene, and different immune responses in females. It prompted us to make acomparison of clinic-pathological changes in the urinary/respiratory system, the severity ofthe disease, and survival rate between males and females affected by EAE.Material & method:Experimental autoimmune encephalomyelitis was induced in female and male Lewis ratsusing guinea pig spinal cord and complete Freund s adjuvant. The animals affected by EAEwere evaluated for weight loss and clinical sign of EAE, survival rate, and some of clinicpathologicalsigns including nasal bleeding, urinary incontinence, and bleeding from urinarytract. Kidney and lung sections were taken from EAE rats at the peak of the disease andhealthy controls, stained with hematoxylin and eosin, and examined with an Olympusmicroscope.Results:Our result indicated that although females are more susceptible to MS, but the disease is moresevere and protractive with higher mortality in males. We also observed clinic-pathologicalsigns including nasal bleeding and urinary incontinence, decreased in females as diseaseprogresses. Inversely in males, nasal bleeding, urinary incontinence, and bleeding fromurinary tract continued by the end of the course of the study. Bleeding from urinary tract wasnot seen in females. Macroscopically, bladder of male rats, but not females, affected by EAEwas full of blood and edematous. In microscopic view of kidney, vascular congestion andlymphocytic inflammation, tubular epithelial cell degeneration & necrosis, glomerularatrophy, pyknotic cells, severe hyperemia, and protein casts within tubules was observed.Microscopic view of lung tissue sections indicated increased arteriolar wall diameter, acuteinflammation/pneumonia, bronchiolitis, severe hyperemia with aboundant hemosiderophages,as well as partial fibrosis and pneumoconiosis. None of the mentioned signs were observed inthe kidney and ling tissue sections from healthy animals.Conclusion:The disease has a protractive pattern and is more severe with higher mortality in males.Clinic-pathological signs decreased in females as disease progresses, but in males itcontinued by the end of the course of the study. Apart from central nervous system lesion,kidney and lung injury may act as synergistic factor for debilitation and mortality.

کلیدواژه ها:

EAE ، Coagulopathy ، Survival Rate ، Sex Influence ، Urinary/Respiratory System