p-Bromophenylacetylurea (BPAU) is a neurotoxin known to cause intraaxonal accumulations of tubulovesicular materials and distal axonal degeneration. This study focused on two aspects of the pathology in the peripheral nerves in rats: (1) the comparative pathology of acute and chronic intoxication, and (2) the ability of intoxicated neurons to regenerate. The rats were divided into acute and chronic intoxication groups. Rats acutely intoxicated received one intraperitoneal injection (400 mg. per kg.) and developed paraparesis after 2 weeks. Rats chronically intoxicated were given daily intraperitoneal injections (10 mg. per kg.) for 2 to 7 months; paraparesis appeared after 8 weeks. Both groups showed degeneration of distal nerves. By 3 weeks, rats in the acute intoxication group showed an 18 to 50 per cent loss of axons in the distal phrenic nerve. Axons contained membranous trabeculae (tubules and vesicles); at later times, the tubulovesicular profiles increased and, subsequently, axons degenerated. In these animals, regenerating sprouts were first seen 3 weeks after stopping BPAU; these sprouts also contained tubulomembranous structures which persisted for 18 months. After 2 to 3 months, the chronic intoxication group showed a reduction in the number of axons in the distal phrenic nerve. Surviving axons showed tubulovesicular profiles similar to those observed in acutely intoxicated rats. In this group of rats, axonal regeneration was also characterized by the presence of membranous profiles in the axonal sprouts. Our observations indicate that the pathologic changes caused by BPAU are independent of the rate of administration of the drug. The long-standing abnormalities in the regenerating sprouts suggest a persistent toxic effect on axons. Since membranes are delivered and retrieved through fast anterograde and retrograde transport, the accumulation of membranes may be related to abnormalities in these systems. BPAU appears to be a useful agent to study the pathogenetic mechanisms causing tubulovesicular neuropathies.
|Original language||English (US)|
|Number of pages||9|
|State||Published - 1982|
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Molecular Biology
- Cell Biology