Amelioration of ethanol-induced neurotoxicity in the neonatal rat central nervous system by antioxidant therapy.
BACKGROUND
The cerebellum of the neonatal rat is highly susceptible to ethanol, with profound loss of Purkinje cells resulting from even brief exposure during the first postnatal week. Developmental ethanol exposure previously has been shown to induce free radicals/oxidative stress processes and/or down-regulate protective antioxidants. In an earlier study, we found antioxidants protected against ethanol neurotoxicity in a tissue culture environment. The present study was designed to determine whether similar protection could be manifested in the intact animal.


METHODS
Neonatal rats were administered a liquid diet via intragastric intubation on postnatal days 4 and 5 (P4-P5), the peak period of ethanol sensitivity in the developing cerebellum. The diet consisted of milk formula with 12% ethanol, the isocaloric substitution of maltose-dextrin for ethanol, or ethanol plus the antioxidant vitamin E. Unbiased three-dimensional counting was utilized to analyze Purkinje cell numbers and density within defined volumes from these animals on P5.


RESULTS
These determinations revealed a substantial loss of Purkinje cells in the ethanol-treated animals compared to controls (approximately 30-44%), but this loss was prevented by the inclusion of vitamin E (601U/100 ml) in the diet. A lower concentration of the antioxidant (301U/100 ml) was not effective in this regard, however.


CONCLUSIONS
These results suggest that ethanol-related cerebellar damage during this early postnatal period may be related to oxidative stress processes or the insufficiency of protective antioxidants. Thus, antioxidant treatment may represent a possible therapy for preventing or ameliorating the central nervous system (CNS) damage seen in the fetal alcohol syndrome.
Heaton
M B
MB
University of Florida Brain Institute, Department of Neuroscience, Gainesville 32610, USA. heaton@ufbi.ufl.edu
Mitchell
J J
JJ
Paiva
M
M
D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology*; D002452:Cell Count / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects / Q000254:growth & development; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D000431:Ethanol / Q000009:adverse effects*; D008297:Male; D011689:Purkinje Cells / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D020318:Rats, Long-Evans; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D002492:Central Nervous System Depressants; D014810:Vitamin E; D000431:Ethanol