TIME-COURSE OF BIOCHEMICAL AND IMMUNOHISTOLOGICAL ALTERATIONS DURING EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS

A comprehensive biochemical, immunological and histological study was undertaken during different stages of experimental allergic encephalom yelitis (EAE). Wistar rats with EAE induced by sensitization with bovi ne myelin showed a maximum decrease of body weight 14-16 days post-ino culation (dpi). coincident with the appearance of the paralysis sympto m (acute period). Quantitation of some brain components indicated a te mporal dissociation among the alterations observed. The higher diminut ion of myelin basic protein (MBP) occurred at 6 dpi and then increased to reach 21 dpi, a normal value. Also, the activity of 2',3'-cyclic n ucleotide 3'-phosphohydrolase was reduced by 40% with respect to contr ol animals only at 6 dpi. The total lipid content was normal; however, among the individual lipids, sulfatides were principally degraded dur ing the acute stage but the amount of cerebrosides was decreased durin g the recovery period (291-40 dpi). Free cholesterol was similar in bo th groups of animals. whereas cholesterol esters were detected in EAE animals from 14 to 40 dpi. Central nervous system meningeal and parenc hymal infiltration with mononuclear cells was recognized principally a t 14 dpi, but some of cells were still present at 40 dpi. Deposits of immunoglobulins in the infiltrated regions as well as in spinal cord m otor neurons were observed among 14-29 dpi. Total circulating antibodi es to MBP began to increase at 14 dpi, reaching a plateau at 21 dpi an d then maintaining this value until 40 dpi. However, the population of anti-MBP antibodies that also recognizes the neuronal protein synapsi n was only present at 14 dpi. The present results suggest that the neu rological symptoms can be related to some early changes in the myelin membrane followed by alterations involving neuronal structures. The ex istence of immunological factors against some epitopes in MBP that als o recognize a synaptosomal protein might account, at least in part, fo r the axonal damage and disruption of the normal interneuronal activit y in EAE and lead together with the alterations in some specific myeli n constituents and the concomitant CNS inflammatory process to the obs erved hindlimb paralysis. Copyright (C) 1996 Elsevier Science Ltd