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CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Defining and Regulating Acute Inflammatory Lesion Formation during the Pathogenesis of Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

Author(s): Christopher Bolton and Paul Smith

Volume 14, Issue 7, 2015

Page: [915 - 935] Pages: 21

DOI: 10.2174/1871527314666150716103629

Price: $65

Abstract

The primary pathology of the human central nervous system 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 central nervous system 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 key primary pathological events in human demyelinating disease.

Keywords: Acute inflammation, EAE-targeted drugs, endothelial cells, experimental autoimmune encephalomyelitis, mast cells, microglia, multiple sclerosis, neutrophils, platelets.


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