Plasma SPARC Elevation in Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

Abstract

Matricellular proteins have been implicated in pathologies after subarachnoid hemorrhage (SAH). To find a new therapeutic molecular target, the present study aimed to clarify the relationships between serially measured plasma levels of a matricellular protein, secreted protein acidic and rich in cysteine (SPARC), and delayed cerebral ischemia (DCI) in 117 consecutive aneurysmal SAH patients with admission World Federation of Neurological Surgeons (WFNS) grades I-III. DCI developed in 25 patients with higher incidences of past history of hypertension and dyslipidemia, preoperative WFNS grade III, modified Fisher grade 4, spinal drainage, and angiographic vasospasm. Plasma SPARC levels were increased after SAH, and significantly higher in patients with than without DCI at days 7-9, and in patients with VASOGRADE-Yellow compared with VASOGRADE-Green at days 1-3 and 7-9. However, there were no relationships between plasma SPARC levels and angiographic vasospasm. Receiver-operating characteristic curves differentiating DCI from no DCI determined the cut-off value of plasma SPARC ≥ 82.1 ng/ml at days 7 - 9 (sensitivity, 0.800; specificity, 0.533; and area under the curve, 0.708), which was found to be an independent determinant of DCI development in multivariate analyses. This is the first study to show that SPARC is upregulated in peripheral blood after SAH, and that SPARC may be involved in the development of DCI without angiographic vasospasm in a clinical setting.

Keywords: Delayed cerebral ischemia; Early brain injury; Matricellular protein; SPARC; Subarachnoid hemorrhage; VASOGRADE.

Fig. 1

A flow chart indicating the included and excluded patients in this study. SAH = subarachnoid hemorrhage, WFNS = World Federation of Neurological Surgeons

Fig. 2

The relationships of plasma levels of secreted protein acidic and rich in cysteine (SPARC) between control patients (n = 10) and patients with subarachnoid hemorrhage (SAH, n = 117; a), between patients with (n = 25) and without delayed cerebral ischemia (DCI) after SAH (n = 92; b), and between patients with SAH of VASOGRADE-Yellow (n = 94) and VASOGRADE-Green (n = 23; c). Data are expressed as means ± standard error of the mean and compared using unpaired t test: *p < 0.001 versus control patient; ^†p < 0.05 versus no DCI; and ^#p < 0.05, and ^##p < 0.01 versus VASOGRADE-Green

Fig. 3

Receiver operating characteristic curve analyses of plasma secreted protein acidic and rich in cysteine (SPARC) levels at days 7 − 9 after subarachnoid hemorrhage to differentiate delayed cerebral ischemia (DCI) from no DCI. The cut-off value of plasma SPARC is 82.1 ng/ml when determined by the Youden index, and 115.7 ng/ml when determined by the point on the curve closest to the (0, 1) point. AUC, area under the curve; CI, confidence interval