The neuromyopathy of vincristine in the guinea pig. An electrophysiological and pathological study

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

This report deals with the toxic effects of vincristine on guinea pigs. The brain, spinal cord, dorsal root ganglia, peripheral nerve, neuromuscular junction and skeletal muscle were studied with the light microscope, and the latter 3 tissues were also examined with the electron microscope. In an acute experiment in which adult guinea pigs received a single intraperitoneal injection of vincristine (1 mg/kg body weight) and were studied at intervals thereafter, the changes of early axonal degeneration occurred with the rapidity of Wallerian degeneration in the sciatic, posterior tibial, digital and intramuscular nerves, and in the terminal axonal expansions of the motor end-plates. Some of the dorsal root ganglia and anterior horn neurons had an increased number of nucleoli, but, like the remainder of the central nervous system, were otherwise normal by light microscopy. There were only minor changes in the subneural apparatus of the motor end-plates. Skeletal muscle underwent rapid degeneration with changes in the longitudinal sarcoplasmic reticulum and the development of complex "spheromembranous bodies". The latter may be derived from the longitudinal sarcoplasmic reticulum. Proximal muscles were more severely involved than distal. In a chronic experiment, adult guinea pigs received twice-weekly intraperitoneal injections of vincristine (0.03 mg/kg body weight) for up to 14 weeks. The sciatic, posterior tibial and digital nerves contained fibres at all stages of axonal degeneration. All fibre sizes and all levels of nerve were affected. Relatively few fibres were involved. The dorsal root ganglia and central nervous system were normal by light microscopy. There was increased branching of terminal intramuscular nerves, an increased number of motor end-plates per muscle fibre, and ultrastructural indications of denervation of many motor end-plates. The skeletal muscle showed no grouped atrophy of denervation. It appears that denervated fibres became rapidly reinnervated by peripheral regeneration of nerves. The skeletal muscle at the end of the chronic experiment was largely normal, though in animals moribund early in the chronic experiment there was gross necrosis and phagocytosis of muscle. Either the muscle became resistant to vincristine or particularly sensitive animals died early. Fatty degeneration of the liver, and dilatation of the bowel and bladder were seen in animals receiving vincristine. The maximum motor nerve conduction velocity in the sciatic nerve fell significantly to 81% of normal after an average of 8 weeks of the chronic experiment, the change occurring in the first few weeks in serial studies. The mechanism of vincristine neurotoxicity is discussed in terms of current concepts of axoplasmic transport and the function of neurotubules and neurofilaments. The biochemical effect of vincristine on skeletal muscle requires further study. In the guinea pig, unlike man, the myopathic effect of vincristine exceeds the neurotoxic.

Original languageEnglish
Pages (from-to)133-162
Number of pages30
JournalJournal of the Neurological Sciences
Volume10
Issue number2
DOIs
StatePublished - Jan 1 1970
Externally publishedYes

Fingerprint

Vincristine
Guinea Pigs
Motor Endplate
Skeletal Muscle
Spinal Ganglia
Muscles
Sarcoplasmic Reticulum
Denervation
Intraperitoneal Injections
Peripheral Nerves
Light
Microscopy
Central Nervous System
Body Weight
Anterior Horn Cells
Wallerian Degeneration
Tibial Nerve
Axonal Transport
Intermediate Filaments
Neuromuscular Junction

ASJC Scopus subject areas

  • Aging
  • Clinical Neurology
  • Surgery
  • Neuroscience(all)
  • Developmental Neuroscience
  • Neurology

Cite this

The neuromyopathy of vincristine in the guinea pig. An electrophysiological and pathological study. / Bradley, Walter G.

In: Journal of the Neurological Sciences, Vol. 10, No. 2, 01.01.1970, p. 133-162.

Research output: Contribution to journalArticle

@article{b119fb724fd04065bf74c4832108dcad,
title = "The neuromyopathy of vincristine in the guinea pig. An electrophysiological and pathological study",
abstract = "This report deals with the toxic effects of vincristine on guinea pigs. The brain, spinal cord, dorsal root ganglia, peripheral nerve, neuromuscular junction and skeletal muscle were studied with the light microscope, and the latter 3 tissues were also examined with the electron microscope. In an acute experiment in which adult guinea pigs received a single intraperitoneal injection of vincristine (1 mg/kg body weight) and were studied at intervals thereafter, the changes of early axonal degeneration occurred with the rapidity of Wallerian degeneration in the sciatic, posterior tibial, digital and intramuscular nerves, and in the terminal axonal expansions of the motor end-plates. Some of the dorsal root ganglia and anterior horn neurons had an increased number of nucleoli, but, like the remainder of the central nervous system, were otherwise normal by light microscopy. There were only minor changes in the subneural apparatus of the motor end-plates. Skeletal muscle underwent rapid degeneration with changes in the longitudinal sarcoplasmic reticulum and the development of complex {"}spheromembranous bodies{"}. The latter may be derived from the longitudinal sarcoplasmic reticulum. Proximal muscles were more severely involved than distal. In a chronic experiment, adult guinea pigs received twice-weekly intraperitoneal injections of vincristine (0.03 mg/kg body weight) for up to 14 weeks. The sciatic, posterior tibial and digital nerves contained fibres at all stages of axonal degeneration. All fibre sizes and all levels of nerve were affected. Relatively few fibres were involved. The dorsal root ganglia and central nervous system were normal by light microscopy. There was increased branching of terminal intramuscular nerves, an increased number of motor end-plates per muscle fibre, and ultrastructural indications of denervation of many motor end-plates. The skeletal muscle showed no grouped atrophy of denervation. It appears that denervated fibres became rapidly reinnervated by peripheral regeneration of nerves. The skeletal muscle at the end of the chronic experiment was largely normal, though in animals moribund early in the chronic experiment there was gross necrosis and phagocytosis of muscle. Either the muscle became resistant to vincristine or particularly sensitive animals died early. Fatty degeneration of the liver, and dilatation of the bowel and bladder were seen in animals receiving vincristine. The maximum motor nerve conduction velocity in the sciatic nerve fell significantly to 81{\%} of normal after an average of 8 weeks of the chronic experiment, the change occurring in the first few weeks in serial studies. The mechanism of vincristine neurotoxicity is discussed in terms of current concepts of axoplasmic transport and the function of neurotubules and neurofilaments. The biochemical effect of vincristine on skeletal muscle requires further study. In the guinea pig, unlike man, the myopathic effect of vincristine exceeds the neurotoxic.",
author = "Bradley, {Walter G}",
year = "1970",
month = "1",
day = "1",
doi = "10.1016/0022-510X(70)90014-6",
language = "English",
volume = "10",
pages = "133--162",
journal = "Journal of the Neurological Sciences",
issn = "0022-510X",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - The neuromyopathy of vincristine in the guinea pig. An electrophysiological and pathological study

AU - Bradley, Walter G

PY - 1970/1/1

Y1 - 1970/1/1

N2 - This report deals with the toxic effects of vincristine on guinea pigs. The brain, spinal cord, dorsal root ganglia, peripheral nerve, neuromuscular junction and skeletal muscle were studied with the light microscope, and the latter 3 tissues were also examined with the electron microscope. In an acute experiment in which adult guinea pigs received a single intraperitoneal injection of vincristine (1 mg/kg body weight) and were studied at intervals thereafter, the changes of early axonal degeneration occurred with the rapidity of Wallerian degeneration in the sciatic, posterior tibial, digital and intramuscular nerves, and in the terminal axonal expansions of the motor end-plates. Some of the dorsal root ganglia and anterior horn neurons had an increased number of nucleoli, but, like the remainder of the central nervous system, were otherwise normal by light microscopy. There were only minor changes in the subneural apparatus of the motor end-plates. Skeletal muscle underwent rapid degeneration with changes in the longitudinal sarcoplasmic reticulum and the development of complex "spheromembranous bodies". The latter may be derived from the longitudinal sarcoplasmic reticulum. Proximal muscles were more severely involved than distal. In a chronic experiment, adult guinea pigs received twice-weekly intraperitoneal injections of vincristine (0.03 mg/kg body weight) for up to 14 weeks. The sciatic, posterior tibial and digital nerves contained fibres at all stages of axonal degeneration. All fibre sizes and all levels of nerve were affected. Relatively few fibres were involved. The dorsal root ganglia and central nervous system were normal by light microscopy. There was increased branching of terminal intramuscular nerves, an increased number of motor end-plates per muscle fibre, and ultrastructural indications of denervation of many motor end-plates. The skeletal muscle showed no grouped atrophy of denervation. It appears that denervated fibres became rapidly reinnervated by peripheral regeneration of nerves. The skeletal muscle at the end of the chronic experiment was largely normal, though in animals moribund early in the chronic experiment there was gross necrosis and phagocytosis of muscle. Either the muscle became resistant to vincristine or particularly sensitive animals died early. Fatty degeneration of the liver, and dilatation of the bowel and bladder were seen in animals receiving vincristine. The maximum motor nerve conduction velocity in the sciatic nerve fell significantly to 81% of normal after an average of 8 weeks of the chronic experiment, the change occurring in the first few weeks in serial studies. The mechanism of vincristine neurotoxicity is discussed in terms of current concepts of axoplasmic transport and the function of neurotubules and neurofilaments. The biochemical effect of vincristine on skeletal muscle requires further study. In the guinea pig, unlike man, the myopathic effect of vincristine exceeds the neurotoxic.

AB - This report deals with the toxic effects of vincristine on guinea pigs. The brain, spinal cord, dorsal root ganglia, peripheral nerve, neuromuscular junction and skeletal muscle were studied with the light microscope, and the latter 3 tissues were also examined with the electron microscope. In an acute experiment in which adult guinea pigs received a single intraperitoneal injection of vincristine (1 mg/kg body weight) and were studied at intervals thereafter, the changes of early axonal degeneration occurred with the rapidity of Wallerian degeneration in the sciatic, posterior tibial, digital and intramuscular nerves, and in the terminal axonal expansions of the motor end-plates. Some of the dorsal root ganglia and anterior horn neurons had an increased number of nucleoli, but, like the remainder of the central nervous system, were otherwise normal by light microscopy. There were only minor changes in the subneural apparatus of the motor end-plates. Skeletal muscle underwent rapid degeneration with changes in the longitudinal sarcoplasmic reticulum and the development of complex "spheromembranous bodies". The latter may be derived from the longitudinal sarcoplasmic reticulum. Proximal muscles were more severely involved than distal. In a chronic experiment, adult guinea pigs received twice-weekly intraperitoneal injections of vincristine (0.03 mg/kg body weight) for up to 14 weeks. The sciatic, posterior tibial and digital nerves contained fibres at all stages of axonal degeneration. All fibre sizes and all levels of nerve were affected. Relatively few fibres were involved. The dorsal root ganglia and central nervous system were normal by light microscopy. There was increased branching of terminal intramuscular nerves, an increased number of motor end-plates per muscle fibre, and ultrastructural indications of denervation of many motor end-plates. The skeletal muscle showed no grouped atrophy of denervation. It appears that denervated fibres became rapidly reinnervated by peripheral regeneration of nerves. The skeletal muscle at the end of the chronic experiment was largely normal, though in animals moribund early in the chronic experiment there was gross necrosis and phagocytosis of muscle. Either the muscle became resistant to vincristine or particularly sensitive animals died early. Fatty degeneration of the liver, and dilatation of the bowel and bladder were seen in animals receiving vincristine. The maximum motor nerve conduction velocity in the sciatic nerve fell significantly to 81% of normal after an average of 8 weeks of the chronic experiment, the change occurring in the first few weeks in serial studies. The mechanism of vincristine neurotoxicity is discussed in terms of current concepts of axoplasmic transport and the function of neurotubules and neurofilaments. The biochemical effect of vincristine on skeletal muscle requires further study. In the guinea pig, unlike man, the myopathic effect of vincristine exceeds the neurotoxic.

UR - http://www.scopus.com/inward/record.url?scp=0014736716&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0014736716&partnerID=8YFLogxK

U2 - 10.1016/0022-510X(70)90014-6

DO - 10.1016/0022-510X(70)90014-6

M3 - Article

C2 - 4314182

AN - SCOPUS:0014736716

VL - 10

SP - 133

EP - 162

JO - Journal of the Neurological Sciences

JF - Journal of the Neurological Sciences

SN - 0022-510X

IS - 2

ER -