Troncoso J C, Griffin J W, Price D L, Hess-Kozlow K M
Lab Invest. 1982 Feb;46(2):215-23.
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 retrogade 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.
对溴苯乙酰脲（BPAU）是一种神经毒素，已知可导致轴突内微管小泡物质积聚和远端轴突变性。本研究聚焦于大鼠周围神经病理学的两个方面：（1）急性和慢性中毒的比较病理学，以及（2）中毒神经元的再生能力。大鼠被分为急性和慢性中毒组。急性中毒的大鼠接受一次腹腔注射（每千克400毫克），2周后出现轻截瘫。慢性中毒的大鼠每天接受腹腔注射（每千克10毫克），持续2至7个月；8周后出现轻截瘫。两组均显示远端神经变性。到3周时，急性中毒组大鼠远端膈神经的轴突损失了18%至50%。轴突含有膜性小梁（小管和小泡）；在后期，微管小泡形态增加，随后轴突变性。在这些动物中，停止使用BPAU 3周后首次见到再生芽；这些芽也含有持续18个月的微管膜结构。2至3个月后，慢性中毒组大鼠远端膈神经的轴突数量减少。存活的轴突显示出与急性中毒大鼠中观察到的类似的微管小泡形态。在这组大鼠中，轴突再生的特征也是轴突芽中存在膜性形态。我们的观察表明，BPAU引起的病理变化与药物给药速率无关。再生芽中长期存在的异常表明对轴突有持续的毒性作用。由于膜是通过快速顺行和逆行运输传递和回收的，膜的积累可能与这些系统的异常有关。BPAU似乎是研究导致微管小泡性神经病的发病机制的有用试剂。
