Neurotoxicology of vincristine in the cat

Abstract

Cats were given vincristine sulfate (50 micrograms/kg i.v. every 4 days) and studied after 7-29 injections when neurological deficits became evident. The conduction velocity spectrum of individual afferent nerves from soleus muscles was shifted toward slower velocities. Relatively few functional muscle spindles or other proprioceptors which responded to muscle stretch were encountered. Those primary endings of soleus muscle spindles which did respond were significantly reduced in dynamic but not length sensitivity. Length sensitivity of secondary endings was unchanged. Thresholds of secondary but not primary endings were elevated. The average conduction velocity of soleus motor axons was reduced 30% but no deficit was detected in motor nerve terminal function. Indirectly-elicited contractile tension of the soleus muscles of the neuropathic cats was not significantly lower than that in untreated animals. Amplitudes of spinal monosynaptic reflexes were unaffected. These data indicate, that in the cat, neurological impairment results partly from dysfunction in muscle spindles and peripheral nerves.

A compartmented neuronal culture system in microdevice format

“…Vincristine is a chemotherapeutic drug whose main side effect is peripheral neuropathy (Bradley et al, 1970;Goldstein et al, 1981;Green et al, 1976;Gregorio et al, 1989;Shiraishi et al, 1985;Tanner et al, 1998aTanner et al, ,b, 2003Vainionpaa et al, 1995). This therapeutic effect is achieved by binding to microtubule proteins of the mitotic spindle causing metaphase arrest.…”

Neuromuscular Disorders in the Cat: Clinical Approach to Weakness

“…The possibility of toxic neuropathy should be considered in cats receiving vincristine that present with a lower motor neuron paresis and/or sensory deficits. 33,34 Trauma Trauma-related neuropathy may be seen in association with a fracture (eg, sciatic nerve dysfunction secondary to a pelvic fracture) or in the absence of orthopaedic disease where the nerve suffers a traction injury at the time of the trauma. Traumatic neuropathies tend to be acute in onset and commonly show an improving clinical course; however, when associated with a fracture, subsequent bone remodelling may cause progressive nerve impingement and dysfunction.…”

Spatiotemporal localization of injury potentials in DRG neurons during vincristine-induced axonal degeneration

“…Vincristine is a chemotherapeutic agent used to treat leukemias and other types of human cancer [5]. Vincristine is also a neurotoxin that causes distal axonal degeneration and peripheral neuropathy, making it a useful and relevant agent for investigations into the process of axonal degeneration [1,6]. We have developed an in vitro model of vincristine neuropathy that recreates the dying back pattern of degeneration [18], and in a standard compartmented culture system we demonstrated that the distal axon is more susceptible than the cell body to the neurotoxic effect of vincristine [15].…”