Neurotoxic effect of vincristine on ultrastructure of hypothalamus in rabbits.
The neurotoxic side-effects are a striking accompaniment of the therapy with vincristine (VCR). Data concerning the influence of VCR on the central nervous system are controversial. In the present study a schedule of VCR treatment was employed to develop the neurotoxic side effects in New Zealand rabbits. In all treated animals neurons were primarily and most severely affected cells. Most of them underwent degeneration. The consecutive stages of the increasing condensation of chromatin and cytoplasm of these cells were observed. Degeneration of the synaptic connections and secondary changes in myelin sheaths of degenerating axons were found. Debris of some death cells were localized intracellularly or as typical apoptotic bodies ingested by some glial cells. Astroglia underwent swelling and their processes separated dying neurons from the surroundings. All the results lead to conclusion that the VCR treatment concomitant with neurotoxic symptoms may affects regions of CNS lacking of blood-brain barrier. Neurons are most vulnerable cells of the brain parenchyma. The changes induced in neurons by the drug are characteristic in many aspects to those described in many cells undergoing apoptosis.
Muzylak
M
M
Laboratory of Developmental Neuropathology, Medical Research Centre Polish Academy of Sciences, Warsaw.
Maślińska
D
D
D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000187:drug effects / Q000648:ultrastructure; D016923:Cell Death / Q000187:drug effects; D002843:Chromatin / Q000187:drug effects / Q000648:ultrastructure; D003593:Cytoplasm / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D007031:Hypothalamus / Q000187:drug effects* / Q000648:ultrastructure*; D008297:Male; D008854:Microscopy, Electron; D008933:Mitochondrial Swelling / Q000187:drug effects; D009186:Myelin Sheath / Q000187:drug effects / Q000648:ultrastructure; D009410:Nerve Degeneration / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure; D011817:Rabbits; D013569:Synapses / Q000187:drug effects / Q000648:ultrastructure; D014750:Vincristine / Q000494:pharmacology / Q000633:toxicity*
D002843:Chromatin; D014750:Vincristine