Inflammation induced neurological handicap processes in multiple sclerosis: new insights from preclinical studies.
Multiple sclerosis (MS) is described as originating from incompletely explained neuroinflammatory processes, dysfunction of neuronal repair mechanisms and chronicity of inflammation events. Blood-borne immune cell infiltration and microglia activation are causing both neuronal destruction and myelin loss, which are responsible for progressive motor deficiencies, organic and cognitive dysfunctions. MRI as a non-invasive imaging method offers various ways to visualise de- and remyelination, neuronal loss, leukocyte infiltration, blood-brain barrier modification and new sensors are emerging to detect inflammatory lesions at an early stage. We describe studies performed on experimental autoimmune encephalomyelitis (EAE) animal models of MS that shed new light on mechanisms of functional impairments to understand the neurological handicap in MS. We focus on examples of neuroinflammation-mediated inhibition of CNS repair involving adult neurogenesis in the sub-ventricular zone and hippocampus and such experimentally observed inhibitions could reflect deficient plasticity and activation of compensatory mechanisms in MS. In parallel with cognitive decline, organic deficits such as bladder dysfunction are described in most of MS patients. Neuropharmacological interventions, electrical stimulation of nerves, MRI and histopathology follow-up studies helped in understanding the operating events to remodel the neurological networks and to compensate the inflammatory lesions both in spinal cord and in cortical regions. At the molecular level, the local production of reactive products is a well-described phenomenon: oxidative species disturb cellular physiology and generate new molecular epitopes that could further promote immune reactions. The translational research from EAE animal models to MS patient cohorts helps in understanding the mechanisms of the neurological handicap and in development of new therapeutic concepts in MS.
Petry
Klaus G
KG
EA2966 Neurobiology of Myelin Pathologies/BP78, University of Bordeaux, 146 Rue Léo-Saignat, 33076 Bordeaux, France. klaus.petry@inserm.fr
Brochet
Bruno
B
Dousset
Vincent
V
Vignes
Jean Rodolphe
JR
Boiziau
Claudine
C
D000818:Animals; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000235:genetics; D009103:Multiple Sclerosis / Q000150:complications / Q000209:etiology / Q000235:genetics; D009422:Nervous System Diseases / Q000209:etiology*