The pathophysiology of acute experimental allergic encephalomyelitis in the rabbit.
Clinical, histological and electrophysiological studies were performed on rabbits with acute experimental allergic encephalomyelitis (EAE). The clinical features were similar to those previously described, with the notable exception of the new findings of areflexia, respiratory slowing and hypothermia. The histological findings were also similar to those previously reported, with inflammatory demyelinating lesions both in the central and peripheral nervous system, especially the dorsal root ganglia. Electrophysiological studies performed one to nine days after the onset of neurological signs demonstrated conduction block in a high proportion of the large diameter afferents in the lumbosacral and thoracic dorsal root ganglia. Single fibre studies with spike-triggered averaging confirmed the conduction block in the dorsal root ganglia. That the conduction block was due to demyelination was indicated by slowing of conduction in large diameter fibres, normal conduction in unmyelinated fibres and the specific effects of temperature and of the potassium channel blocking agent, 4-aminopyridine. These conduction abnormalities in the peripheral nervous system, focused on the dorsal root ganglia, account for the postural disturbance, hypotonia, ataxia and areflexia in rabbits with EAE. Such conduction block is likely to mask the expression of any lesions of the central nervous system that alone could produce similar signs. The implications of these findings for the human demyelinating diseases are discussed.
D000344:Afferent Pathways / Q000503:physiopathology; D000818:Animals; D001833:Body Temperature Regulation; D001921:Brain / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology / Q000503:physiopathology*; D005727:Ganglia, Spinal / Q000503:physiopathology; D008297:Male; D009046:Motor Neurons / Q000502:physiology; D009186:Myelin Sheath / Q000648:ultrastructure; D009431:Neural Conduction; D009469:Neuromuscular Junction / Q000503:physiopathology; D011817:Rabbits; D012021:Reflex, Abnormal / Q000503:physiopathology; D012119:Respiration; D013116:Spinal Cord / Q000473:pathology; D013126:Spinal Nerve Roots / Q000473:pathology / Q000503:physiopathology; D009435:Synaptic Transmission