Cerebrolysin increases motor recovery and decreases inflammation in a mouse model of autoimmune encephalitis.

ABSTRACT

Multiple sclerosis (MS) is a complex chronic neurodegenerative disease that involves an abnormal autoimmune response directed against the brain, nerves and spinal cord; it is considered the most frequent cause of neurological disability, because MS-associated inflammatory lesions can affect a wide range of systems to a varying degree and may cause a plethora of neurological comorbidities and symptoms. The symptoms are quite variable from patient to patient and depend on the spatial distribution of the central nervous system (CNS) lesions, but usually involve sensory disturbances, cognitive deficits, unilateral vision loss, bladder dysfunction, ataxia, fatigue, double vision, weakness of the limbs and intestinal disorders. Experimental autoimmune encephalitis (EAE) mouse model reproduces the pathological features of the human disease, and is a widely used model used for studying the pathology and different treatment options in the preclinical stage. In this study, we aimed to evaluate the motor function, as well as the degree of demyelination and inflammatory changes in the brains of mice immunized for the myelin oligodendrocyte glycoprotein (MOG)35-55, and treated with Cerebrolysin. Animals were randomly assigned to one of the three groups (i) EAE untreated group (n=10), (ii) EAE treated group (n=10), and (iii) control group (n=5), and their motor dysfunction was followed until the clinical pathology begun to improve. We also analyzed histologically and immunohistochemically the lesions in the optical nerves, cervical spinal cord and medulla. Our results showed higher deficit scores for untreated animals compared to treated animals. After harvesting the tissue, we have first evaluated the density of myelin in the optical nerves, cervical spinal cord and medulla and we found significant differences between treated and untreated groups of animals. We continued to investigate the structure of the CNS parenchyma by evaluating the intensity and morphology of the neuronal cytoskeleton and microglia by immunohistochemical stainings. Although larger animal groups are necessary, this is the first pilot study to investigate the use of a neurotrophic factor as a putative treatment option for a MS model.