Cerebrospinal fluid markers of idiopathic intracranial hypertension: Is the renin-angiotensinogen system involved?

Abstract

Background: The causes underlying idiopathic intracranial hypertension (IIH) are poorly understood. Methods: To identify disease-related biomarkers that could offer a new insight into IIH pathology, we analyzed the cerebrospinal fluid (CSF) of 18 patients with IIH and 18 controls using two-dimensional fluorescence differential in-gel electrophoresis (2-D DIGE). Results: We found six proteins that were upregulated in IIH (sterol regulatory element-binding protein 1, zinc-alpha-2-glycoprotein, immunoglobulin heavy constant alpha 1 [IGHA1], alpha-1-antitrypsin [SERPINA1], serotransferrin, haptoglobin) and four proteins that were downregulated (hemopexin, angiotensinogen, vitamin-D-binding protein, transthyretin). The validity of our approach was confirmed for one candidate protein (angiotensinogen). To account for a dependency from blood-CSF barrier function, the ratio of angiotensinogen and albumin CSF-to-serum quotients (Qang/Qalb) was determined, which confirmed the downregulation of angiotensinogen in IIH ( p = .04). Conclusion: Previous studies showed the intrinsic renin-angiotensin system (RAS) to regulate choroid plexus blood flow and CSF production. Altered levels of angiotensinogen could indicate an imbalance of the RAS in IIH that may provide new targets for therapeutic intervention.