Department of Neurosurgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
Center for Vessels and Heart, Mie University Hospital, Tsu, Japan.
Neurotherapeutics. 2019 Apr;16(2):480-490. doi: 10.1007/s13311-018-00707-y.
Delayed cerebral ischemia (DCI) is a serious complication of aneurysmal subarachnoid hemorrhage (SAH). Matricellular protein periostin (POSTN) has been found to be upregulated and linked with early brain injury after experimental SAH. The aim of the present study was to investigate the relationship between plasma POSTN levels and various clinical factors including serum levels of C-reactive protein (CRP), an inflammatory marker, in 109 consecutive SAH patients whose POSTN levels were measured at days 1-12 after aneurysmal obliteration. DCI developed in 16 patients associated with higher incidence of angiographic vasospasm, cerebral infarction, and 90-day worse outcomes. POSTN levels peaked at days 4-6 before DCI development. Cerebrospinal fluid (CSF) drainage was associated with reduced POSTN levels, but did not influence CRP levels. There was no correlation between POSTN levels and other treatments or CRP levels. To predict DCI development, receiver-operating characteristic curves indicated that the most reasonable cutoff POSTN levels were obtained at days 1-3 in patients without CSF drainage (80.5 ng/ml; specificity, 77.6%; sensitivity, 85.7%). Multivariate analyses using variables obtained by day 3 revealed that POSTN level was an independent predictor of DCI. POSTN levels over the cutoff value were associated with higher incidence of DCI, but not angiographic vasospasm. This study shows for the first time that CSF drainage may reduce plasma POSTN levels, and that POSTN levels may increase prior to the development of DCI with and without vasospasm irrespective of systemic inflammatory reactions in clinical settings. These findings suggest POSTN as a new therapeutic molecular target against post-SAH DCI.
迟发性脑缺血（DCI）是蛛网膜下腔出血（SAH）的严重并发症。基质细胞蛋白骨桥蛋白（POSTN）已被发现在上实验性 SAH 后上调，并与早期脑损伤相关。本研究旨在探讨 109 例连续 SAH 患者的血浆 POSTN 水平与各种临床因素之间的关系，这些患者在动脉瘤闭塞后第 1-12 天测量了 POSTN 水平。16 例患者发生 DCI，与血管痉挛、脑梗死和 90 天预后较差的发生率较高有关。POSTN 水平在发生 DCI 前的第 4-6 天达到峰值。脑脊液（CSF）引流与 POSTN 水平降低有关，但不影响 CRP 水平。POSTN 水平与其他治疗方法或 CRP 水平之间无相关性。为了预测 DCI 的发生，ROC 曲线表明，在没有 CSF 引流的患者中，第 1-3 天的最合理 POSTN 截断值为 80.5ng/ml（特异性为 77.6%；敏感性为 85.7%）。使用第 3 天获得的变量进行多变量分析表明，POSTN 水平是 DCI 的独立预测因子。超过临界值的 POSTN 水平与 DCI 的发生率较高有关，但与血管痉挛无关。本研究首次表明，CSF 引流可能降低血浆 POSTN 水平，并且在有或没有血管痉挛的情况下，POSTN 水平可能在 DCI 发生之前升高，而与临床环境中的全身炎症反应无关。这些发现表明 POSTN 可能成为针对 post-SAH DCI 的新治疗分子靶标。
