| Objective: Optic neuritis(ON) is an acute or subacute inflammation or demyelinate process.The study'objective were to (1)Observe the pathological changes of optic nerve in EAE,which is a model of simulate inflammatory aspectd of Multiple Sclerosis(MS). Apply the model of EAE for the reseach of demyelinated optic neuritis, establishing an experiment platform for demyelinated optic neuritis. (2)Determine the expression of NF-200,Fas ,further to evaluate efficacy and mechanism of Nimodipine and provide some experimental evidences for clinical therapies in demyelinated optic neuritis.Methods: (1)Twelve female experimental Wistar rats were inoculated intradermal injuction with the emulsion homogenate contained spinal cord of guinea pig and complete Freund's adjuvant in feet(four rats in 8,12,18,30 day afterimmunization,respectively).Four female rats in normal control group. We have investigated the clinical signs and scores of the scale of Koh's standard. The 8th day,12th day,18th day,30th day after initial immunization,rats were killed respectively. The changes of optic nerve were observed by HE staining,myelin sheath specific staining and electron microscopes. (2)Thirty-six experimental rats were assigned to three groups randomly:four rats in normal control group; sixteen rats in EAE model group and sixteen rats in Nimodipine treated group(four rats in 8,12,18,30 day afterimmunization,respectively). The rats were given Nimodipine by oral gavage from the first day to 30th day after initial immunization. The dosage of Nimodipine was 1mg.kg-1.d-1. The rats in normal control group and EAE model group were treated in stead of equal normal saline(N.S). We have investigated the clinical signs and scores of the scale of Koh's standard.The 8th day,12th day,18th day,30th day after initial immunization,rats were killed respectively. We detect the expression of neurofilament and Fas in optic nerves by immunohistochemical method.Results: (1)The animal model we induced showed typical clinical characters and the pathological changes of EAE. We can see the pathological changes of the optic nerve in EAE. Demyelination occurs in the optic nerve.Under light microscope,the optic nerve fibers showed bulb-like degeneration,the axis irregularity swelling, phlegmonosis cell infiltrating,a quantity of glial cell and collagen tissue formed hyperplastic tissue.Under electron microscopy,the axons showed bulb-like degeneration,myelin sheaths were loose, microtubule and microfilament disappeared. (2)In EAE model group, the expression of NF200 in optic nerve was significantly decreased at different test times. The number of NF200 positive axons and myelins in Nimodipine group in optic nerve was significantly more than that in EAE model group(P<0.05) and less than that in normal group(P<0.05). Moreover, the number of NF200 positive axons was correlated with the number of myelins.The expression of Fas in optic nerve was significantly less than that in EAE model group(P<0.05).Conclusions: (1)The method of eatablishing the model of EAE was stable and reliable in our study. We can see serious pathological changes of optic nerve in EAE model group .the EAE animal model can be used for the reseach of demyelinated optic neuritis. (2) Ca2+agonists(Nimodipine) can up-regulation the expression of NF200,down-regulation the expression of Fas in optic nerve. The calcum channel block agent (Nimodipine) has a marked axonal protection in optic neuritis of MS possibly by reducing Ca2+ influx. preventing Ca2+ overload,inhibiting deleterious enzymes.
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