Transient cortical astrogliosis induced by alcohol exposure during the neonatal brain growth spurt in rats.
The astrocyte response to central nervous system injury induced by neonatal alcohol exposure was evaluated using radioimmunoassay and immunocytochemistry of glial fibrillary acidic protein (GFAP). Rat pups were exposed to alcohol on postnatal days 4 through 9 via artificial rearing. Alcohol solutions were administered as one of the following treatments: 10.2% (v/v) in two feedings (4.5 g/kg/day), 5.1% (v/v) in four feedings (4.5 g/kg/day), or 2.5% (v/v) in 12 feedings (6.6 g/kg/day), producing mean blood alcohol concentrations (BACs) of approximately 300, 180, and 50 mg/dl, respectively. Littermates were included as gastrostomy controls (GC) and suckle controls (SC). On postnatal day 10, GFAP concentration increased as a function of BAC, and the 10.2% alcohol treatment significantly and dramatically increased GFAP in the cortex (325% of SC). GFAP immunocytochemistry revealed frequent loci of heavily labeled reactive astrocytes surrounding small cortical blood vessels in the 10.2% group. In addition, a generalized increase in GFAP immunoreactivity was present in the deep layers of the cortex in all alcohol groups, marked by astrocytic fibrillary hypertrophy and increased density. Three-dimensional counts in layer V of parietal cortex using confocal microscopy indicated that the density of GFAP-labeled astrocytes of the 10.2% group was twice that of controls. The layer V gliosis was observable even at low BACs, while gliosis around the vasculature occurred only with high BACs. By postnatal day 15, the astroglial effects were no longer evident. These transient astroglial reactions likely constitute an important aspect of cortical pathophysiology resulting from binge alcohol exposure during the brain growth spurt of the third trimester equivalent.
Goodlett
C R
CR
Department of Anatomy, University of Iowa, Iowa City 52242.
Leo
J T
JT
O'Callaghan
J P
JP
Mahoney
J C
JC
West
J R
JR
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006128:Growth / Q000187:drug effects*; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D008297:Male; D015999:Multivariate Analysis; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley
D005904:Glial Fibrillary Acidic Protein; D000431:Ethanol