Department of Neurosurgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Japan.
Int J Mol Sci. 2022 Dec 2;23(23):15184. doi: 10.3390/ijms232315184.
Aneurysmal subarachnoid hemorrhage (SAH) is a poor-outcome disease with a delayed neurological exacerbation. Fibulin-5 (FBLN5) is one of matricellular proteins, some of which have been involved in SAH pathologies. However, no study has investigated FBLN5's roles in SAH. This study was aimed at examining the relationships between serially measured plasma FBLN5 levels and neurovascular events or outcomes in 204 consecutive aneurysmal SAH patients, including 77 patients (37.7%) with poor outcomes (90-day modified Rankin Scale 3-6). Plasma FBLN5 levels were not related to angiographic vasospasm, delayed cerebral ischemia, and delayed cerebral infarction, but elevated levels were associated with severe admission clinical grades, any neurological exacerbation and poor outcomes. Receiver-operating characteristic curves indicated that the most reasonable cut-off values of plasma FBLN5, in order to differentiate 90-day poor from good outcomes, were obtained from analyses at days 4-6 for all patients (487.2 ng/mL; specificity, 61.4%; and sensitivity, 62.3%) and from analyses at days 7-9 for only non-severe patient (476.8 ng/mL; specificity, 66.0%; and sensitivity, 77.8%). Multivariate analyses revealed that the plasma FBLN5 levels were independent determinants of the 90-day poor outcomes in both all patients' and non-severe patients' analyses. These findings suggest that the delayed elevation of plasma FBLN5 is related to poor outcomes, and that FBLN5 may be a new molecular target to reveal a post-SAH pathophysiology.
颅内动脉瘤性蛛网膜下腔出血(SAH)是一种预后不良的疾病,会出现迟发性神经恶化。纤维结合蛋白 5(FBLN5)是一种基质细胞蛋白,其中一些与 SAH 病理有关。然而,尚无研究调查 FBLN5 在 SAH 中的作用。本研究旨在检测 204 例连续颅内动脉瘤性 SAH 患者的血清 FBLN5 水平与神经血管事件或结局之间的关系,其中包括 77 例(37.7%)预后不良患者(90 天改良 Rankin 量表 3-6 分)。血清 FBLN5 水平与血管造影性血管痉挛、迟发性脑缺血和迟发性脑梗死均无相关性,但高水平与严重入院临床评分、任何神经恶化和不良预后相关。受试者工作特征曲线表明,为了区分 90 天的良好和不良预后,在所有患者的第 4-6 天(487.2ng/ml;特异性 61.4%;敏感性 62.3%)和仅非严重患者的第 7-9 天(476.8ng/ml;特异性 66.0%;敏感性 77.8%)分析中获得的血清 FBLN5 的最佳截断值能够最好地区分 90 天的预后。多变量分析表明,血清 FBLN5 水平是所有患者和非严重患者分析中 90 天不良预后的独立决定因素。这些发现表明,血清 FBLN5 的延迟升高与不良预后有关,FBLN5 可能是揭示 SAH 后病理生理学的新分子靶点。