Hara Mutsuya, Tamaki Masashi, Aoyagi Masaru, Ohno Kikuo
Department of Neurosurgery, School of Medicine, Tokyo Medical and Dental University, Japan.
J Med Dent Sci. 2009 Sep;56(3):101-6.
Inflammatory cytokines are reportedly involved in the pathogenesis of chronic subdural hematomas (CSH), and the angiogenesis of hematomas has particularly been in focus. Cyclooxygenase-2 (COX-2) is an essential enzyme for the synthesis of prostaglandin E2 (PGE2). The COX-2-PGE2 pathway has been shown to influence angiogenic factors such as vascular endothelial growth factor (VEGF). We investigated the association of COX-2 expression in the dura mater and outer membrane with the pathogenesis of CSH, and suggested a treatment strategy on the basis of this association. Hematoma fluid and serum samples obtained from 37 patients, and samples of the dura mater and outer CSH membrane obtained from 13 patients during the operation were examined in this study. The concentrations of PGE2 in relation to COX-2 in the hematoma fluid were significantly higher than those in the serum. Immunohistochemical analyses revealed COX-2-positive cells in the outer membrane of CSHs. There was a linear and significant relationship between PGE2 concentration in hematoma fluid and the interval from trauma to initial surgery. COX-2 may play a crucial role during the development of CSHs. Our study might lead to the development of anti-COX-2 treatment options that aim to minimize repeat surgery and choose medical therapy by reducing CSH morbidity and recurrence rate in patients with CSH.
据报道，炎性细胞因子参与慢性硬膜下血肿（CSH）的发病机制，血肿的血管生成尤其受到关注。环氧化酶-2（COX-2）是前列腺素E2（PGE2）合成所必需的酶。COX-2-PGE2途径已被证明会影响血管内皮生长因子（VEGF）等血管生成因子。我们研究了硬脑膜和外膜中COX-2表达与CSH发病机制的关系，并基于这种关系提出了一种治疗策略。本研究检测了37例患者的血肿液和血清样本，以及13例患者手术中获取的硬脑膜和CSH外膜样本。血肿液中与COX-2相关的PGE2浓度显著高于血清中的浓度。免疫组化分析显示CSH外膜中有COX-2阳性细胞。血肿液中PGE2浓度与外伤至初次手术的间隔时间呈线性显著关系。COX-2可能在CSH的发展过程中起关键作用。我们的研究可能会促成抗COX-2治疗方案的开发，旨在通过降低CSH患者的发病率和复发率，尽量减少再次手术并选择药物治疗。
