Dietrich W D, Truettner J, Zhao W, Alonso O F, Busto R, Ginsberg M D
Department of Neurological Surgery, University of Miami School of Medicine, Florida 33101, USA.
J Neurotrauma. 1999 Jul;16(7):567-81. doi: 10.1089/neu.1999.16.567.
This study documents the regional and temporal patterns of glial fibrillary acidic protein (GFAP) RNA and protein expression after parasagittal fluid-percussion (F-P) brain injury (1.7 to 2.2 atm) in male Sprague-Dawley rats. In situ hybridization was conducted in 28 rats with a 35S-labeled antisense riboprobe to GFAP at 0.5, 2, and 6 hours and 1, 3, and 30 days after traumatic brain injury (TBI) or sham procedures. Immunocytochemical staining of GFAP was conducted in 20 rats at 1, 3, 7, and 30 days after TBI or sham procedures. At 0.5 and 2 hours after TBI, increased GFAP mRNA was restricted to superficial cortical areas underlying the impact site. At 24 hours, increased GFAP mRNA was observed throughout the traumatized hemisphere except within the histopathologically vulnerable lateral parietal cortex and external capsule. Contralateral expression within the hippocampus and cingulate and lateral cortices was also observed. Three days after TBI, GFAP mRNA expression was prominent overlying pial surfaces, in cortical regions surrounding the contusion, and within the hippocampus and lateral thalamus. Immunocytochemical visualization of GFAP at 1 and 3 days demonstrated reactive astrocytes overlying the pial surface, surrounding the cortical contusion, and within ipsilateral white matter tracts, hippocampus, and lateral thalamus. At 30 days, GFAP mRNA and protein expression were present within the deeper cortical layers of the lateral somatosensory cortex and lateral thalamus and throughout ipsilateral white matter tracts. These data demonstrate a complex pattern of GFAP mRNA and protein expression within gray and white matter tracts following F-P brain injury. Patterns of GFAP gene expression may be a sensitive molecular marker for evaluating the global response of the brain to focal injury in terms of progressive neurodegenerative as well as regenerative processes.
本研究记录了雄性Sprague-Dawley大鼠矢状旁流体冲击(F-P)脑损伤(1.7至2.2个大气压)后胶质纤维酸性蛋白(GFAP)RNA和蛋白表达的区域及时间模式。对28只大鼠进行了原位杂交,在创伤性脑损伤(TBI)或假手术操作后的0.5、2和6小时以及1、3和30天,使用35S标记的针对GFAP的反义核糖探针。对20只大鼠在TBI或假手术操作后的1、3、7和30天进行了GFAP的免疫细胞化学染色。TBI后0.5和2小时,GFAP mRNA增加仅限于撞击部位下方的浅表皮质区域。24小时时,在整个受创伤的半球观察到GFAP mRNA增加,但在组织病理学上易损的外侧顶叶皮质和外囊内未观察到。在海马体、扣带回和外侧皮质的对侧也观察到了表达。TBI后三天,GFAP mRNA表达在软脑膜表面、挫伤周围的皮质区域以及海马体和外侧丘脑内显著。在1天和3天时GFAP的免疫细胞化学可视化显示,软脑膜表面、皮质挫伤周围以及同侧白质束、海马体和外侧丘脑内有反应性星形胶质细胞。30天时,GFAP mRNA和蛋白表达存在于外侧体感皮质和外侧丘脑的较深皮质层以及同侧整个白质束中。这些数据表明,F-P脑损伤后GFAP mRNA和蛋白在灰质和白质束中的表达模式复杂。GFAP基因表达模式可能是一种敏感的分子标志物,用于从进行性神经退行性变以及再生过程方面评估大脑对局灶性损伤的整体反应。