Magnetic resonance imaging of antibody-mediated demyelinating experimental allergic encephalomyelitis.
Two models of demyelinating experimental allergic encephalomyelitis (EAE) were studied on Lewis rats in whom the disease was induced by injections of either (i) lentil-lectin binding myelin glycoproteins plus myelin basic protein (MBP)-specific T cells (36 rats), or (ii) myelin/oligodendrocyte glycoprotein-specific monoclonal antibody plus MBP-specific T cells (16 rats). In our 24 control rats, 20 received MBP-specific T cells only, and four received myelin glycoproteins plus purified protein derivative-specific T cells. The extent of the resulting blood-brain barrier (BBB) permeability, vasogenic oedema and/or demyelination was assessed in vivo using magnetic resonance imaging (MRI) techniques. The results show that in both demyelinating EAE models the disease appeared more quickly, progressed very rapidly and was more severe than when induced with a similar number of MBP-specific T cells alone. Almost all animals developed hyperacute EAE, with a very high mortality rate. MRI showed a very intense BBB breakdown and vasogenic oedema in all the normally 'leaky' areas of the central nervous system, and focal lesions corresponding to plaque formation in the brain stem or spinal cord near the 'leaky' areas. During the 40-day observation period, the rare survivors of this hyperacute form of EAE presented a chronic form of EAE with serious sequelae. Our results demonstrate that the synergistic effect observed between MBP-specific T cells and antibodies to myelin glycoproteins, especially to myelin/oligodendrocyte glycoprotein, does not only induce demyelinating lesions and chronic clinical signs, but is further responsible, via the normally 'leaky areas', for the fatal increase of the BBB breakdown and vasogenic oedema of which there are ample acute clinical signs.
Namer
I J
IJ
Institut de Physique Biologique (URA 1173 CNRS), Faculté de Médecine, Strasbourg, France.
Steibel
J
J
Piddlesden
S J
SJ
Mohr
M
M
Poulet
P
P
Chambron
J
J
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001812:Blood-Brain Barrier; D002493:Central Nervous System Diseases / Q000473:pathology; D003711:Demyelinating Diseases / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D004487:Edema / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D008279:Magnetic Resonance Imaging; D051381:Rats; D011917:Rats, Inbred Lew
D000906:Antibodies