Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
J Neuroinflammation. 2011 Mar 8;8:22. doi: 10.1186/1742-2094-8-22.
Although cyclooxygenases (COX) and prostaglandin E synthases (PGES) have been implicated in ischemic stroke injury, little is known about their role in intracerebral hemorrhage (ICH)-induced brain damage. This study examines the expression and cellular localization of COX-1, COX-2, microsomal PGES-1 (mPGES-1), mPGES-2, and cytosolic PGES (cPGES) in mice that have undergone hemorrhagic brain injury.
ICH was induced in C57BL/6 mice by intrastriatal injection of collagenase. Expression and cellular localization of COX-1, COX-2, mPGES-1, mPGES-2, and cPGES were examined by immunofluorescence staining.
In the hemorrhagic brain, COX-1, mPGES-2, and cPGES were expressed constitutively in neurons; COX-1 was also constitutively expressed in microglia. The immunoreactivity of COX-2 was increased in neurons and astrocytes surrounding blood vessels at 5 h and then tended to decrease in neurons and increase in astrocytes at 1 day. At 3 days after ICH, COX-2 was observed primarily in astrocytes but was absent in neurons. Interestingly, the immunoreactivity of mPGES-1 was increased in neurons in the ipsilateral cortex and astrocytes in the ipsilateral striatum at 1 day post-ICH; the immunoreactivity of astrocytic mPGES-1 further increased at 3 days.
Our data suggest that microglial COX-1, neuronal COX-2, and astrocytic COX-2 and mPGES-1 may work sequentially to affect ICH outcomes. These findings have implications for efforts to develop anti-inflammatory strategies that target COX/PGES pathways to reduce ICH-induced secondary brain damage.
环氧化酶（COX）和前列腺素 E 合酶（PGES）已被认为与缺血性中风损伤有关，但它们在脑出血（ICH）引起的脑损伤中的作用知之甚少。本研究检查了在经历出血性脑损伤的小鼠中 COX-1、COX-2、微粒体 PGES-1（mPGES-1）、mPGES-2 和胞质 PGES（cPGES）的表达和细胞定位。
通过纹状体内注射胶原酶在 C57BL/6 小鼠中诱导 ICH。通过免疫荧光染色检查 COX-1、COX-2、mPGES-1、mPGES-2 和 cPGES 的表达和细胞定位。
在出血性脑内，COX-1、mPGES-2 和 cPGES 在神经元中持续表达；COX-1 也在小胶质细胞中持续表达。COX-2 的免疫反应性在 5 小时时在血管周围的神经元和星形胶质细胞中增加，然后在神经元中趋于减少，在星形胶质细胞中增加。在 ICH 后 3 天，COX-2 主要在星形胶质细胞中观察到，但在神经元中不存在。有趣的是，mPGES-1 的免疫反应性在 ICH 后 1 天在对侧皮质的神经元和同侧纹状体的星形胶质细胞中增加；星形胶质细胞的 mPGES-1 免疫反应性在 3 天进一步增加。
我们的数据表明，小胶质细胞 COX-1、神经元 COX-2 和星形胶质细胞 COX-2 和 mPGES-1 可能依次作用以影响 ICH 结果。这些发现对于开发针对 COX/PGES 途径的抗炎策略以减少 ICH 引起的继发性脑损伤具有重要意义。
