Elevated Cellular Retinoic Acid Binding Protein-I in Cerebrospinal Fluid of Patients with Hemorrhagic Cerebrovascular Diseases : Preliminary Study

Objective : Elevated cellular retinoic acid binding protein-I (CRABP-I) is thought to be related to the abnormal proliferation and migration of smooth muscle cells (SMCs). Accordingly, a higher CRABP-I level could cause disorganized vessel walls by causing immature SMC phenotypes and altering extracellular matrix proteins which could result in vulnerable arterial walls with inadequate responses to hemodynamic stress. We hypothesized that elevated CRABP-I level in the cerebrospinal fluid (CSF) could be related to subarachnoid hemorrhage (SAH). Moreover, we-also extended this hypothesis in patients with vascular malformation according to the presence of hemorrhage. Methods : We investigated the CSF of 26 patients : SAH, n=7; unruptured intracranial aneurysm (UIA), n=7; arteriovenous malformation (AVM), n=4; cavernous malformation (CM), n=3; control group, n=5. The optical density of CRABP-I was confirmed by Western blotting and presented as mean standard error of the measurement. Results : CRABP-I in SAH (0.33+/-0.09) was significantly higher than that in the UIA (0.12+/-0.01, p=0.033) or control group (0.10+/-0.01, p=0.012). Hemorrhage presenting AVM (mean 0.45, ranged 0.30-0.59) had a higher CRABP-I level than that in AVM without hemorrhage presentation (mean 0.16, ranged 0.14-0.17). The CRABP-I intensity in CM with hemorrhage was 0.21 and 0.31, and for CM without hemorrhage 0.14. Overall, the hemorrhage presenting group (n=11, 0.34+/-0.06) showed a significantly higher CRABP-I intensity than that of the non-hemorrhage presenting group (n=10, 0.13+/-0.01, p=0.001). Conclusion : The results suggest that elevated CRABP-I in the CSF could be related with aneurysm rupture. Additionally, a higher CRABP-I level seems to be associated with hemorrhage development in vascular malformation.