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. (/sup 3/H)Thymidine ((/sup 3/H)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 (/sup 3/H)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 (/sup 3/H)ara-C confirmed that this drug entered lesioned brain tissue, although at levels considerably lower than those found in the periphery. Cyclophosphamide also reduced (/sup 3/H)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 (/sup 3/H)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.
- Research Organization:
- Department of Pharmacology, George Washington University School of Medicine, Washington, DC
- OSTI ID:
- 6709457
- Journal Information:
- J. Pharmacol. Exp. Ther.; (United States), Vol. 222:3
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CEREBRAL CORTEX
BIOLOGICAL REGENERATION
TRITIUM COMPOUNDS
TRACER TECHNIQUES
ANTIMITOTIC DRUGS
BIOSYNTHESIS
CELL PROLIFERATION
DNA
THYMIDINE
AZINES
BIOLOGICAL RECOVERY
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
CEREBRUM
DRUGS
HETEROCYCLIC COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
NERVOUS SYSTEM
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PYRIMIDINES
RECOVERY
RIBOSIDES
SYNTHESIS
551001* - Physiological Systems- Tracer Techniques
550201 - Biochemistry- Tracer Techniques
550301 - Cytology- Tracer Techniques