Effects of DNA synthesis inhibitors on post-traumatic glial cell proliferation.
This study attempts to inhibit post-traumatic glial cell scarring in rats lesioned in the frontal cortex, by treatment with several antiproliferative drugs. [3H]Thymidine ([3H]TdR) incorporation into DNA served as the biochemical index of glial cell proliferation and histological observations confirmed the biochemical effects. Cytosine arabinoside (ara-C), given i.p. at a total daily dosage of 15 to 100 mg/kg, was found to inhibit the incorporation of [3H]TdR into cortical DNA and also inhibited the proliferation of glial cells after cortical trauma. Treatment using ara-C induced marked histological changes in glial cells near the lesion, indicating that the inhibition by the drug of DNA synthesis correlated with cytotoxicity to proliferating glial cells. Experiments using [3H]ara-C confirmed that this drug entered lesioned brain tissue, although at levels considerably lower than those found in the periphery. Cyclophosphamide also reduced [3H]TdR incorporation into both lesioned and control cortices; however, this effect, unlike that of ara-C, was not proportionately greater in the lesioned cortex. Vincristine, but not vinblastine, also inhibited [3H]TdR incorporation into the lesioned cortex, possibly reflecting differences in the neuronal uptake of the vinca alkaloids. We propose that ara-C can inhibit the proliferation of glial cells after neural trauma and that judicious use of this agent may lessen scarring in the injured central nervous system, possibly enhancing the regenerative capacity of the brain.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D003520:Cyclophosphamide / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology; D004247:DNA / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects; D009457:Neuroglia / Q000166:cytology* / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D014747:Vinblastine / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
D000970:Antineoplastic Agents; D003561:Cytarabine; D014316:Tritium; D014750:Vincristine; D014747:Vinblastine; D003520:Cyclophosphamide; D004247:DNA; D013936:Thymidine