Asada Reona, Nakatsuka Yoshinari, Kanamaru Hideki, Kawakita Fumihiro, Fujimoto Masashi, Miura Yoichi, Shiba Masato, Yasuda Ryuta, Toma Naoki, Suzuki Hidenori
Department of Neurosurgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
Transl Stroke Res. 2021 Oct;12(5):808-816. doi: 10.1007/s12975-020-00886-x. Epub 2021 Jan 9.
A matricellular protein osteopontin (OPN) is considered to exert neuroprotective and healing effects on neurovascular injuries in an acute phase of aneurysmal subarachnoid hemorrhage (SAH). However, the relationships between OPN expression and chronic shunt-dependent hydrocephalus (SDHC) have never been investigated. In 166 SAH patients (derivation and validation cohorts, 110 and 56, respectively), plasma OPN levels were serially measured at days1-3, 4-6, 7-9, and 10-12 after aneurysmal obliteration. The OPN levels and clinical factors were compared between patients with and without subsequent development of chronic SDHC. Plasma OPN levels in the SDHC patients increased from days 1-3 to days 4-6 and remained high thereafter, while those in the non-SDHC patients peaked at days 4-6 and then decreased over time. Plasma OPN levels had no correlation with serum levels of C-reactive protein (CRP), a systemic inflammatory marker. Univariate analyses showed that age, modified Fisher grade, acute hydrocephalus, cerebrospinal fluid drainage, and OPN and CRP levels at days 10-12 were significantly different between patients with and without SDHC. Multivariate analyses revealed that higher plasma OPN levels at days 10-12 were an independent factor associated with the development of SDHC, in addition to a more frequent use of cerebrospinal fluid drainage and higher modified Fisher grade at admission. Plasma OPN levels at days 10-12 maintained similar discrimination power in the validation cohort and had good calibration on the Hosmer-Lemeshow goodness-of-fit test. Prolonged higher expression of OPN may contribute to the development of post-SAH SDHC, possibly by excessive repairing effects promoting fibrosis in the subarachnoid space.
基质细胞蛋白骨桥蛋白（OPN）被认为在动脉瘤性蛛网膜下腔出血（SAH）急性期对神经血管损伤具有神经保护和愈合作用。然而，OPN表达与慢性分流依赖性脑积水（SDHC）之间的关系从未被研究过。在166例SAH患者（分别为推导队列和验证队列，各110例和56例）中，在动脉瘤闭塞后的第1 - 3天、4 - 6天、7 - 9天和10 - 12天连续测量血浆OPN水平。比较了发生和未发生慢性SDHC的患者之间的OPN水平和临床因素。SDHC患者的血浆OPN水平从第1 - 3天到第4 - 6天升高，此后保持在较高水平，而非SDHC患者的血浆OPN水平在第4 - 6天达到峰值，然后随时间下降。血浆OPN水平与全身炎症标志物C反应蛋白（CRP）的血清水平无相关性。单因素分析显示，年龄、改良Fisher分级、急性脑积水、脑脊液引流以及第10 - 12天的OPN和CRP水平在发生和未发生SDHC的患者之间存在显著差异。多因素分析显示，除了更频繁地使用脑脊液引流和入院时改良Fisher分级较高外，第10 - 12天较高的血浆OPN水平是与SDHC发生相关的独立因素。第10 - 12天的血浆OPN水平在验证队列中保持了相似的鉴别能力，并且在Hosmer - Lemeshow拟合优度检验中具有良好的校准。OPN的持续高表达可能通过促进蛛网膜下腔纤维化的过度修复作用，导致SAH后SDHC的发生。
