Traumatic brain injury leads to increased expression of peripheral-type benzodiazepine receptors, neuronal death, and activation of astrocytes and microglia in rat thalamus
Traumatic brain injury leads to increased expression of peripheral-type benzodiazepine receptors, neuronal death, and activation of astrocytes and microglia in rat thalamus
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DOI：
10.1006/exnr.1999.7269
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发表时间：
2000-01-01
影响因子：
5.3
通讯作者：
Dempsey, RJ
中科院分区：
文献类型：
--
作者：
Rao, VLR;Dogan, A;Dempsey, RJ
在哺乳动物中枢神经系统中，外周型苯二氮卓受体（PTBR）定位于星形胶质细胞和小胶质细胞内的线粒体外膜上。PTBR将胆固醇转运到神经类固醇生物合成的位点。据报道，几种神经退行性疾病与PTBR密度增加相关。在本研究中，我们评估了PTBR密度和基因表达的变化，在大鼠的大脑作为一个功能的时间（6小时至14天）创伤性脑损伤（TBI）后。假手术大鼠作为对照。TBI后3 ~ 14天，PTBR拮抗剂[H-3] PK 11195的结合率显著增加（106 ~ 185%，P < 0.01），PTBR mRNA表达显著增加（2 ~ 3.4倍，P < 0.01）。伤后14天，同侧丘脑神经元数目明显减少（减少85 ~ 90%，P < 0.01）。在同一时间点，同侧丘脑也出现胶质细胞酸性蛋白阳性细胞增多（星形胶质细胞，接近3.5倍）和艾德-1阳性细胞（小胶质细胞/巨噬细胞，相似于36倍），已知与PTBR相关的两种细胞类型，TBI后PTBR表达的增加似乎与小胶质细胞/巨噬细胞相关，而不是星形胶质细胞，因为TBI后不同时期的PTBR密度与艾德的数量相关性更好。1阳性细胞数（r（2）= 0.95）高于GFAP阳性细胞数（r（2）= 0.56）。TBI诱导的PTBR表达增加可能是对细胞损伤的适应性反应，并可能在TBI的病理生理学中发挥作用。(C)北京大学出版社.
In mammalian CNS, the peripheral-type benzodiazepine receptor (PTBR) is localized on the outer mitochondrial membrane within the astrocytes and microglia. PTBR transports cholesterol to the site of neurosteroid biosynthesis. Several neurodegenerative disorders were reported to be associated with increased densities of PTBR. In the present study, we evaluated the changes in the PTBR density and gene expression in the brains of rats as a function of time (6 h to 14 days) after traumatic brain injury (TBI). Sham-operated rats served as control. Between 3 and 14 days after TBI, there was a significant increased in the binding of PTBR antagonist [H-3]PK11195 (by 106 to 185%, P < 0.01, as assessed by quantitative autoradiography and in vitro filtration binding) and PTBR mRNA expression (by 2- to 3.4-fold, P < 0.01, as assessed by RT-PCR) in the ipsilateral thalamus. At 14 days after the injury, the neuronal number decreased significantly (by 85 to 90%, P < 0.01) in the ipsilateral thalamus. At the same time point, the ipsilateral thalamus also showed increased numbers of the glial fibrillary acidic protein positive cells (astrocytes, by similar to 3.5-fold) and the ED-1 positive cells (microglia/macrophages, by similar to 36-fold), the two cell types known to be associated with PTBR, Increased PTBR expression following TBI seems to be associated with microglia/macrophages than astrocytes as PTBR density at different periods after TBI correlated better with the number of ED-1 positive cells (r(2) = 0.95) than the GFAP positive cells (r(2) = 0.56). TBI-induced increased PTBR expression is possibly an adaptive response to cellular injury and may play a role in the pathophysiology of TBI. (C) 2000 Academic Press.