Ultrastructural studies of the dying-back process. I. Peripheral nerve terminal and axon degeneration in systemic acrylamide intoxication.

Abstract

The spatio-temporal pattern of distal peripheral nerve, sensory and motor nerve terminal, degeneration in experimental acrylamide neuropathy has been examined. Tissue was sampled from limbs of cats throughout various stages of intoxication (e.g. 7–32 days of 10 mg/kg/day and up to 294 days of 3 mg/kg/day of acrylamide) and examined by light and electron microscopy. Nerve terminals of a few Pacinian corpuscles in hindfoot and forefoot toepads displayed the first abnormalities, before the onset of clinical signs; filopod axon processes were lost, axolemmas disappeared and axoplasm was phagocytosed by inner core cells. Degeneration of adjacent primary annulospiral endings of muscle spindles in hindfoot muscle began shortly after the first changes in Pacinian corpuscle axons. Later, juxtaposed secondary muscle spindle endings and motor nerve terminals, supplying nearby extrafusal muscle fibers, began to degenerate. These sensory and motor nerve terminals accumulated neurofilaments, became swollen and disappeared. Contemporaneous with the early degenerative changes in some nerve terminals, seattered preterminal nodes, and their paranodes, displayed focal axonal accumulations of neurofilaments, mitochondria and dense bodies. These organelle conglomerations were associated with focal axonal swelling and paranodal retraction of myelin. This axonal change appeared to spread along internodes and to lead to fiber degeneration with the formation of ovoids which were later replaced by bands of Büngner. Fiber degeneration proceeded proximally as intoxication progressed. Above the proximal limit of fiber breakdown, axons displayed progressively fewer abnormalities in the form of adaxonal Schwann cell ingrowths and swollen paranodal regions. The cardinal conclusions of this study of acrylamide neuropathy are: 1-some distal sensory nerve endings (Pacinian corpuscle and annulospiral terminals) in the hindfeet begin to degenerate before adjacent motor nerve terminals supplying extrafusal muscles, and 2− the distal tips of the largest and longest axons are not most vulnerable, although there is a propensity for long and large axons to die-back first. In view of these observations, the etiology of the dying-back process requires re-examination.