Experimental brain injury induces differential expression of tumor necrosis factor-alpha mRNA in the CNS

Experimental brain injury induces differential expression of tumor necrosis factor-alpha mRNA in the CNS
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DOI:
10.1016/0169-328x(95)00274-v
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发表时间:
1996-03-01
期刊:
MOLECULAR BRAIN RESEARCH
影响因子:
--
通讯作者:
McIntosh, TK
McIntosh, TK
中科院分区:
其他
文献类型:
--
作者:
Fan, L;Young, PR;McIntosh, TK

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在本研究中,我们研究了肿瘤坏死因子-α(TNF-α)mRNA的表达在特定的大脑区域后,实验性侧液压冲击创伤性脑损伤(TBI)的大鼠。将成年Sprague-Dawley大鼠(n = 42)用戊巴比妥钠(60 mg/kg,i. p.)并经受中度严重性(2.4atm.)以左颞顶皮层为中心,或“假”治疗(麻醉和手术无损伤)。在损伤后1、6或24 h断头处死动物,取出脑,并制备左(损伤)顶叶皮质(LC)、右顶叶皮质(RC)、左相邻皮质(LA)、右相邻皮质(RA)、左海马(LH)和右海马(RH)的组织样品。分离总RNA并进行北方印迹杂交。TNF-α mRNA表示为巨噬细胞(阳性对照)RNA的相对放射性百分比。在假手术或未处理动物中,在任何时间在六个脑区的任何一个中均未观察到TNF-α mRNA表达的一致变化(小于5%)。伤后1h,TNF-α mRNA在LH(104 ± 17,P < 0.05)、LC(105 ± 21,P < 0.05)和LA(69 ± 8,P < 0.01)中的表达明显增加。TNF-α mRNA表达在伤后6 h在LH(46 +/- 8,P < 0.05)、LC(30 +/- 3,P < 0.01)和LA(32 +/- 3,P < 0.01)中也观察到增加,但在伤后24 h消退。在对侧半球,RH组TNF-α mRNA表达在1h时增加(46 +/- 2,P < 0.01),RA组在6 h时增加(26 +/-6%,P < 0.05)。这些结果表明,以下旁液压冲击脑损伤,TNF-α mRNA的时间表达的改变,在特定的大脑区域,包括那些非创伤性半球。创伤后TNF-α基因表达的改变可能在CNS创伤的急性和再生反应中起重要作用。
In the present study, we examined the expression of tumor necrosis factor-alpha (TNF-alpha) mRNA in specific brain regions following experimental lateral fluid percussion traumatic brain injury (TBI) in rats. Adult Sprague-Dawley rats (n = 42) were anesthetized with sodium pentobarbital (60 mg/kg, i.p.) and subjected to lateral fluid percussion brain injury of moderate severity (2.4 atm.) centered over the left temporoparietal cortex, or 'sham' treatment (anesthesia and surgery without injury). Animals were killed by decapitation at 1, 6 or 24 h post injury, brains removed, and tissue samples of left (injured) parietal cortex (LC), right parietal cortex (RC), left adjacent cortex (LA), right adjacent cortex (RA), left hippocampus (LH) and right hippocampus (RH) were prepared. Total RNA was isolated and Northern blot hybridization was performed. TNF-alpha mRNA is expressed as the percent relative radioactivity of macrophage (positive control) RNA. In sham or naive animals, no consistent changes in expression of TNF-alpha mRNA were observed in any of the six brain areas at any times (less than 5%). A marked increase of TNF-alpha mRNA expression was observed in LH (104 +/- 17, P < 0.05 compared with sham), LC (105 +/- 21, P < 0.05) and LA (69 +/- 8, P < 0.01) in the traumatized hemisphere 1 h following injury. An increased TNF-alpha mRNA expression was also observed in LH (46 +/- 8, P < 0.05), LC (30 +/- 3, P < 0.01) and LA (32 +/- 3, P < 0.01) at 6 h which resolved by 24 h following injury. In the contralateral hemisphere, expression of TNF-alpha mRNA was increased in RH (46 +/- 2, P < 0.01) at 1 h and in RA (26 +/- 6%, P < 0.05) at 6 h. These results indicate that following parasagittal fluid percussion brain injury, the temporal expression of TNF-alpha mRNA is altered in specific brain regions, including those of the non-traumatized hemisphere. Post-traumatic alteration in gene expression of TNF-alpha might play an important role in both the acute and regenerative response to CNS trauma.