The effects of taxol on the central nervous system response to physical injury.
Cytoskeletal disruption is a key pathological change in numerous human neurodegenerative diseases. We have, therefore, examined the effect of taxol, a microtubule-stabilising agent, on the neuronal response to localised trauma in the central nervous system utilising a rodent experimental model that replicates cytoskeletal alterations which occur in conditions such as Alzheimer's disease and head injury. At 1 day post-injury, 1 mM taxol administration to the damaged neocortex resulted in a statistically significant reduction in the density of abnormal neurites labelled with antibodies to neurofilaments. In addition, there was a relative preservation of MAP2 labelling of dendrites surrounding the injury site in taxol-treated, as compared to vehicle-treated, animals at 1 day post-injury. At 4 days post-injury, however, there was a statistically significant increase in the density of abnormal neurites surrounding the injury site in taxol-treated rats as compared to vehicle-treated animals. The degree of MAP2 labelling was also equally decreased in both vehicle- and taxol-treated animals as compared to normal cortex at this time point. Our data suggest that, in the short term, taxol may be stabilising neuronal microtubules and reducing reactive alterations in axons. After longer periods, however, our data indicate that the stereotypical neuronal reaction to trauma may be abnormally prolonged due to taxol administration, consistent with both in vivo work on taxol intoxication in the injured peripheral nervous system and in vitro culture studies.
Adlard
P A
PA
Department of Pathology, University of Tasmania, Hobart, Australia.
King
C E
CE
Vickers
J C
JC
D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D003599:Cytoskeleton / Q000187:drug effects; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D019579:Neocortex / Q000187:drug effects* / Q000293:injuries* / Q000473:pathology; D016900:Neurofilament Proteins / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values
D008869:Microtubule-Associated Proteins; D016900:Neurofilament Proteins; D017239:Paclitaxel