Genetic and Histological Alterations Reveal Key Role of Prostaglandin Synthase and Cyclooxygenase 1 and 2 in Traumatic Brain Injury-Induced Neuroinflammation in the Cerebral Cortex of Rats Exposed to Moderate Fluid Percussion Injury.
Genetic and Histological Alterations Reveal Key Role of Prostaglandin Synthase and Cyclooxygenase 1 and 2 in Traumatic Brain Injury-Induced Neuroinflammation in the Cerebral Cortex of Rats Exposed to Moderate Fluid Percussion Injury.
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DOI：
10.1177/0963689717715169
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发表时间：
2017-07
影响因子：
3.3
通讯作者：
Mabuchi T
中科院分区：
文献类型：
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作者：
Shojo H;Borlongan CV;Mabuchi T
在创伤性脑损伤（TBI）的初始损伤之后，发生与神经炎症密切相关的继发性神经变性。前列腺素（PG）脱氢酶和环氧合酶（考克斯）1和2可能有助于大脑中的炎症。创伤后PG和COX 1和2的时空表达特征可能指导抗神经炎症策略的发展。在这里，我们研究了PG合成酶信号和COX 1和2基因表达水平和考克斯-1和2阳性细胞类型及其在TBI诱导的大脑中的时间定位，以揭示它们参与疾病的神经炎症的发展。使用大脑皮层的大鼠进行横向中度液压冲击损伤（FPI）的TBI模型的大脑样本，我们试图表征的时间（亚急性TBI）和空间（外侧皮质病变）的大脑变化伴随着疾病的进展。采用微阵列通路分析比较了假手术和TBI治疗大鼠之间PG合酶信号转导的时间基因表达变化。此外，我们研究了COX 1和2的表达模式和它们的细胞内分布在假手术和TBI治疗的大鼠免疫组织化学。FPI后，COX 1和COX 2基因表达水平升高，PGE 2合成酶表达水平升高，而PGD 2合成酶表达水平降低，提示PGE 2和PGD 2分别具有抗炎和抗炎的拮抗作用。免疫组织化学分析显示，COX 1和COX 2在大脑中均以时间依赖性方式增加，特别是在皮质变性神经元中。有趣的是，考克斯细胞类型的表达是细胞特异性的，因为COX 1在变性神经元中特别增加，而COX 2在巨噬细胞中表达。鉴于PG、COX 1和2基因在受损脑中的动态时空表达和定位，调节PG合酶和COX 1和2活性将需要仔细的疾病特异性定制治疗，以消除由TBI引起的神经炎症困扰的继发性细胞死亡。
After the initial insult in traumatic brain injury (TBI), secondary neurodegeneration occurs that is intimately associated with neuroinflammation. Prostaglandin (PG) synthases and cyclooxygenase (COX) 1 and 2 may contribute to inflammation in the brain. Temporal and spatial expression features of PG and COX1 and 2 following trauma may guide the development of antineuroinflammation strategies. Here, we examined PG synthase signaling and COX1 and 2 gene expression levels and COX-1- and 2-positive cell types and their temporal localization in TBI-induced brain in an effort to reveal their participation in the disease’s evolving neuroinflammation. Using brain samples from the cerebral cortex of rats subjected to TBI model of lateral moderate fluid percussion injury (FPI), we sought to characterize the temporal (subacute TBI) and spatial (lateral cortical lesion) brain alterations accompanying the disease progression. Temporal gene expression changes of PG synthase signaling were compared between sham-operated and TBI-treated rats using microarray pathway analysis. Moreover, we examined COX1 and 2 expression patterns and their intracellular distribution in sham-operated and TBI-treated rats by immunohistochemistry. After FPI, COX1 and 2 gene expression levels, and PGE2 synthase increased while PGD2 synthase decreased, suggesting that PGE2 and PGD2 afforded contraindicative effects of inflammation and anti-inflammation, respectively. Immunohistochemical analyses showed that both COX1 and COX2 increased in a time-dependent manner in the brain, specifically in degenerating neurons of the cortex. Interestingly, the expression of COX cell type was cell-specific, in that COX1 was particularly increased in degenerating neurons while COX2 was expressed in macrophages. In view of the dynamic temporal and spatial expression of PG, COX1 and 2 gene expression and localization in the injured brain regulating PG synthase and COX1 and 2 activity will require a careful disease-specific tailoring of treatments to abrogate the neuroinflammation-plagued secondary cell death due to TBI.
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影响因子：
5.1
作者：
Fu, Ruying;Shen, Qingyu;Xu, Pengfei;Luo, Jin Jun;Tang, Yamei
通讯作者：
Tang, Yamei
影响因子：
4.2
作者：
Dash, PK;Mach, SA;Moore, AN
通讯作者：
Moore, AN
影响因子：
34.7
作者：
Brown, Guy C.;Neher, Jonas J.
通讯作者：
Neher, Jonas J.
影响因子：
82.9
作者：
Gilroy, DW;Colville-Nash, PR;Willoughby, DA
通讯作者：
Willoughby, DA
DOI：
10.1038/jcbfm.2009.223
发表时间：
2010-02
期刊：
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子：
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通讯作者：
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