Goodlett C R, Leo J T, O'Callaghan J P, Mahoney J C, West J R
Department of Anatomy, University of Iowa, Iowa City 52242.
Brain Res Dev Brain Res. 1993 Mar 19;72(1):85-97. doi: 10.1016/0165-3806(93)90162-4.
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.
利用放射免疫分析法以及胶质纤维酸性蛋白（GFAP）免疫细胞化学法，评估新生大鼠酒精暴露诱导的中枢神经系统损伤后的星形胶质细胞反应。通过人工饲养，在出生后第4天至第9天给幼鼠喂食酒精。酒精溶液按以下处理方式之一给药：两次喂食10.2%（体积/体积）（4.5克/千克/天）、四次喂食5.1%（体积/体积）（4.5克/千克/天）或12次喂食2.5%（体积/体积）（6.6克/千克/天），分别产生平均血酒精浓度（BAC）约为300、180和50毫克/分升。同窝幼鼠作为胃造口对照（GC）和哺乳对照（SC）。在出生后第10天，GFAP浓度随BAC升高而增加，10.2%酒精处理组皮质中的GFAP显著大幅增加（为SC组的325%）。GFAP免疫细胞化学显示，10.2%组小皮质血管周围频繁出现大量标记的反应性星形胶质细胞位点。此外，所有酒精处理组皮质深层的GFAP免疫反应性普遍增加，表现为星形胶质细胞纤维肥大和密度增加。使用共聚焦显微镜对顶叶皮质V层进行三维计数表明，10.2%组GFAP标记的星形胶质细胞密度是对照组的两倍。即使在低BAC水平下，V层也可观察到胶质增生，而只有在高BAC水平下血管周围才会出现胶质增生。到出生后第15天，星形胶质细胞的影响不再明显。这些短暂的星形胶质细胞反应可能是孕晚期大脑快速发育阶段暴饮酒精所致皮质病理生理学的一个重要方面。
