Smith, Paul and Bolton, Christopher (2015) Defining and regulating acute inflammation in lesion formation during the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis. CNS & Neurological Disorders – Drug Targets, 14 (7). pp. 915-935. ISSN 1996-3181

Abstract

The primary pathology of the human central nervous system (CNS) disease multiple sclerosis (MS) and the animal counterpart experimental autoimmune encephalomyelitis (EAE) includes immunological and inflammatory events. Immune system involvement in MS has been widely debated but the role of inflammation has received less attention. Classic acute inflammation features vasculitis, resident tissue macrophage and mast cell participation plus the involvement of circulatory-derived neutrophils and platelets. Pre-lesion development in MS incorporates cerebral vasculitis, activated resident microglia in normal appearing white matter together with infiltrating cell types and factors indicative of an acute inflammatory reaction.
Similarly, the formation of perivascular lesions during early EAE includes characteristic neurovasculitis, the participation of CNS microglial phenotypes plus haemopoietic cells and mediators, signifying an ongoing acute inflammatory response.
EAE has been extensively used as a screen to select drugs for MS treatment but has been criticised as unrepresentative of the human condition due to fundamental differences in disease induction and pathogenesis.
The review provides compelling evidence for a distinct acute inflammatory phase in MS lesion formation that is convincingly reproduced in early EAE pathology. Moreover, consideration of drug efficacy studies undertaken during initial EAE validates the occurrence of an acute inflammatory phase in disease pathogenesis. Critical appraisal, recognition and acceptance of the mutual acute inflammatory components inherent in the primary pathology of MS and EAE reveals new targets and encourages confident and reliable employment of the animal model in the assessment of novel compounds for the control of critical primary pathological events in human demyelinating disease.

Item Type:	Article
Keywords:	acute inflammation, endothelial cells, experimental autoimmune encephalomyelitis, EAE-targeted drugs, mast cells, microglia, multiple sclerosis, neutrophils, platelets
Date Deposited:	26 Apr 2016 23:45
Last Modified:	26 Apr 2016 23:45
URI:	https://oak.novartis.com/id/eprint/24840