Chronic Relapsing EAE: Its Application to Study of Human Inflammatory Demyelinating Diseases

Abstract

In 1933, Rivers et al. [23] reported that they had observed an encephalomyelitis with myelin destruction in 2 of 8 monkeys that had received repeated IM injections of aqueous emulsion and alcohol-ether extracts of normal rabbit brain. Two years later, Rivers and Schwentker [22] confirmed these original observations, stressing that 7 of 8 monkeys developed demyelinating encephalomyelitis. The procedure used by Rivers et al., followed by confirming reports by Ferraro and Jervis [3], involved repeated (46–85) IM injections of aqueous emulsions and alcohol-ether extracts of normal brain. This technique produced morphological lesions of various ages and sizes, and gave a very low mortality rate. However, it was very time consuming (3 inoculations a week, up to 85 injections) and difficult to apply to small animals. Since the goal of these experiments was to determine what component of brain tissue causes demyelinating encephalomyelitis, there was a great need for a method which would shorten the time and procedure required to induce the disease. This was solved when Freund and McDermott [5] demonstrated a new technique of emulsifying antigens in various adjuvants in aquafor, paraffin oil, and heat-killed tubercle bacilli. This technique facilitated the experimental production of encephalomyelitis and the inception of its symptoms with one or two injections of brain emulsion in Freund’s adjuvant [15].