Effect Of Pleiotrophin On Blood-brain Barrier Permeability In Experimental Autoimmune Encephalomyelitis Mice

Objective:Multiple sclerosis(MS)is an autoimmune disease characterized by inflammatory demyelinating lesions of the white matter in the central nervous system(CNS).Changes in the blood-brain barrier(BBB)of central nervous system(CNS)are the basic pathological signs of MS.Therefore,repairing or reversing BBB injury a key is step in the reversible and controllable treatment of MS.Pleiotrophin(PTN)is a vascular growth factor,which has the functions of promoting cell growth,migration and promoting nervous system development.In this experiment,experimental autoimmune encephalomyelitis(EAE)mice were used to investigate the effects of PTN on blood-brain barrier permeability of MS.Method:EAE was induced by immunizing 6-8 weeks old 18-20 g C57BL/6 female mice with myelinoligodendrocyte glyeoprotein(MOG)35-55 peptides.From the 7th day after immunization,PTN was injected into the cerebellum and the medulla oblongata every 3 days as the experimental group(PTN group).The control group and the EAE group were set as controls.Nerve function scores were recorded daily,Evans Blue permeability experiments,spinal cord H&E staining,spinal Luxol Fast Blue(LFB)staining,myelin basic protein(MBP)fluorescent staining,ICAM-1 immunohistochemical staining and Western Blot for measurement of tight protein expression were used to evaluate the effects of PTN on neurological function scores,the extent of inflammation in central nervous system,the integrity of the blood-brain barrier.Results:EAE mice have blood-brain barrier disruption,and the more severe the symptoms,the more obvious the BBB disruption.Compared with the EAE group,the neurological symptoms of the mice were significantly reduced in the PTN group;the inflammation was reduced in the PTN group by H&E staining;through the detection of Evans blue permeability experiments in the brain;BBB tight junction(claudin-5,occludin,zo-1)damage protein assays to demonstrate that PTN can protect the integrity of BBB.Interestingly,the expression level of extracellular matrix metalloproteinase 9(MMP9)has been thought to be related to MS-induced BBB damage,while PTN can inhibit MMP9 expression.Conclusion:This study demonstrates that Pleiotrophin can improve neurological function in experimental autoimmune encephalomyelitis mice,reduce their inflammatory response and demyelination,and maintain the integrity of the blood-brain barrier.It provides new therapeutic targets and ideas for multiple sclerosis.