Fan L, Young P R, Barone F C, Feuerstein G Z, Smith D H, McIntosh T K
Division of Neurosurgery, University of Pennsylvania, Philadelphia 19104, USA.
Brain Res Mol Brain Res. 1996 Mar;36(2):287-91. doi: 10.1016/0169-328x(95)00274-v.
In the present study, we examined the expression of tumor necrosis factor-alpha (TNF-alpha) mRNA i 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.
在本研究中，我们检测了实验性大鼠侧方流体冲击性脑损伤（TBI）后特定脑区肿瘤坏死因子-α（TNF-α）mRNA的表达。成年Sprague-Dawley大鼠（n = 42）用戊巴比妥钠（60 mg/kg，腹腔注射）麻醉，然后在左颞顶叶皮质进行中度严重程度（2.4个大气压）的侧方流体冲击性脑损伤，或进行“假手术”治疗（麻醉和手术但无损伤）。在损伤后1、6或24小时通过断头处死动物，取出大脑，并制备左（损伤）顶叶皮质（LC）、右顶叶皮质（RC）、左邻接皮质（LA）、右邻接皮质（RA）、左海马（LH）和右海马（RH）的组织样本。提取总RNA并进行Northern印迹杂交。TNF-α mRNA以巨噬细胞（阳性对照）RNA的相对放射性百分比表示。在假手术或未受伤的动物中，在任何时间六个脑区中的任何一个中均未观察到TNF-α mRNA表达的一致变化（小于5%）。在损伤后1小时，在受伤半球的LH（104±17，与假手术组相比P < 0.05）、LC（105±21，P < 0.05）和LA（69±8，P < 0.01）中观察到TNF-α mRNA表达显著增加。在损伤后6小时，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TNF-α mRNA表达增加，至损伤后24小时恢复。在对侧半球，TNF-α mRNA表达在1小时时在RH（46±2，P < 0.01）增加，在6小时时在RA（26±6%，P < 0.05）增加。这些结果表明，矢状旁流体冲击性脑损伤后，TNF-α mRNA的时间表达在特定脑区发生改变，包括未受伤半球的脑区。TNF-α基因表达的创伤后改变可能在中枢神经系统创伤的急性和再生反应中起重要作用。
