Increased plasma pigment epithelium-derived factor (PEDF) concentrations as a negative predictor of angiographic vasospasm after aneurysmal subarachnoid hemorrhage

Abstract

Cerebral vasospasm remains a major determinant of delayed cerebral ischemia (DCI) and poor outcomes after aneurysmal subarachnoid hemorrhage (SAH). This study was aimed to investigate if a matricellular protein pigment epithelium-derived factor (PEDF) can be a biomarker of angiographic vasospasm (aVSP) after SAH. In 197 consecutive patients with aneurysmal SAH, plasma PEDF concentrations were serially measured at days 1–––12 post-SAH. Plasma PEDF concentrations in SAH patients were elevated compared with patients with unruptured cerebral aneurysms, and especially higher in patients with admission World Federation of Neurological Surgeons (WFNS) grades IV–V. However, higher plasma PEDF concentrations at days 1–3 and 10–12 were associated with no development of aVSP. In an analysis limited to 72 non-sedated patients with preoperative WFNS grades I–III, plasma PEDF concentrations were also significantly higher in patients with neither DCI nor aVSP. Multivariate analysis showed that increased plasma PEDF concentration at days 1–3 was an independent predictor of no development of aVSP. This was the first study to measure plasma PEDF concentrations and to show the relationships with aVSP development in SAH patients. PEDF may act protectively against aVSP, and serve as a negative biomarker and a target for drug discovery for aVSP.