Cyclophilin A in Ruptured Intracranial Aneurysm

Cyclophilin A (CyPA), an oxidative stress-induced factor, was found to play an important role in the aneurysm formation. Our working hypothesis was that the plasma level of CyPA in ruptured intracranial aneurysm could predict the neurological outcome. From 2011 to 2013, a total of 36 patients with ruptured saccular intracranial aneurysm were recruited in our study. Before coil embolization, we draw blood samples at the orifice of a culprit aneurysm and in the remote peripheral vein for measurements of the CyPA levels. We utilized the modified Rankin scale 30 days after aneurysm rupture as the outcome measure. Generalized linear models were used to estimate the adjusted odds ratios of the poor neurological outcome given the presence of high plasma level of CyPA. The aneurysmal and venous CyPA levels were significantly associated with the initial clinical severity (P1⁄4 0.004 and 0.03, respectively) and 30-day outcome (P1⁄4 0.01 and 0.02, respectively). The aneurysmal CyPA levels modestly correlated with age and high Fisher grade (r1⁄4 0.39 and 0.41; P1⁄4 0.02 and 0.01, respectively). The aneurysmal CyPA levels strongly correlated with the venous counterpart (r1⁄4 0.89; P< 0.001). Patients with high levels of aneurysmal CyPA were 15.66 times (95% CI, 1.48–166.24; P1⁄4 0.02) more likely to have worse neurological outcome than those with the low levels after adjustment of the age, gender, and the documented confounding factors. High plasma level of CyPA is a significant prognostic biomarker for poor neurological outcome in patients with ruptured intracranial ei-Liang Chen, MD uo, MS, n-San Liu, MD, PhD, and Ching-Po Lin, PhD Abbreviations: CT = computed tomography, CyPA = cyclophilin A, SAH = subarachnoid hemorrhage. INTRODUCTION S ubarachnoid hemorrhage (SAH) resulting from rupture of intracranial aneurysms is a highly fatal condition with a mortality rate as high as 50% in the 1st month. Although vasospasm was the main cause of mortality and morbidity after aneurysm rupture, the CONSCIOUS-2 trial showed no significant effect of clazosentan, an endothelin receptor antagonist, on preventing vasospasm-related sequelae. These disappointing results might indicate complex and uncertain pathophysiology of the cerebral vasospasm in patients with SAH. In addition to vasospasm, established predisposing factors for poor clinical outcome after aneurysmal SAH include older age, female gender, hypertension, smoking, and larger amount SAH on admission computed tomography (CT). In addition, manifestation of both local and systemic inflammation has been shown to associate with worse clinical outcome. Cyclophilin A (CyPA), a specific secreted oxidative stressinduced factor, is ubiquitously distributed and abundantly expressed in vascular smooth muscle cells. In addition to multiple intracellular functions, such as immunophilins and components of the cell cycle, CyPA has extracellular roles in inflammatory diseases such as rheumatoid arthritis and atherosclerosis. The characteristic pathological features of an aneurysm are intense oxidative stress, inflammation, and apoptosis of smooth muscle cells. In an animal study of abdominal aortic aneurysm, Satoh et al showed that intracellular and extracellular CyPA, derived from vascular smooth muscle cells, plays an important role in the formation of an aneurysm. Furthermore, Piechota-Polanczyk et al found decreased tissue levels of CyPA in simvastatin-treated patients with abdominal aortic aneurysm. However, to our knowledge, the clinical implication of CyPA in ruptured intracranial aneurysmal microenvironment has not been investigated. The purpose of our study was to investigate the associations between the neurological outcome and CyPA levels, measured both at the orifice of ruptured saccular intracranial ote peripheral vein. Our hypothesis was that manifestation of high plasma CyPA is a prognostic biomarker for worsening clinical course.