J Korean Neurosurg Soc.  2015 Feb;57(2):88-93. 10.3340/jkns.2015.57.2.88.

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

• Jeon JP
• Cho WS
• Kang HS
• Kim JE
• Kim SK
• Oh CW

• KMID: 2191188
• DOI: http://doi.org/10.3340/jkns.2015.57.2.88

Abstract

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.

Keyword

Cerebrospinal fluid; Arteriovenous malformation; Cavernous malformation; Retinoic acid

MeSH Terms

Aneurysm
Arteriovenous Malformations
Blotting, Western
Cerebrospinal Fluid*
Extracellular Matrix Proteins
Hemodynamics
Hemorrhage
Humans
Intracranial Aneurysm
Myocytes, Smooth Muscle
Phenotype
Rupture
Subarachnoid Hemorrhage
Tretinoin*
Vascular Malformations
Extracellular Matrix Proteins
Tretinoin

Figure

• 

  Fig. 1 Western blot analysis of cellular retinoic acid binding protein-I (CRABP-I) expression in cerebrospinal fluid from patients with subarachnoid hemorrhage (SAH), unruptured intracranial aneurysm (UIA), arteriovenous malformation (AVM) presenting with and without hemorrhage, cavernous malformation (CM), and control group. The albumin level was used for normalization.

• 

  Fig. 2 Graph shows the optical density of cellular retinoic acid binding protein-I (CRABP-I) in the cerebrospinal fluid from patients presenting with subarachnoid hemorrhage (SAH), unruptured intracranial aneurysm (UIA) and the control group. CRABP-I optical density in SAH (0.33±0.09) was significantly higher than that in UIA (0.12±0.01, p=0.033) or the control group (0.10±0.01, p=0.012). There was no significant difference in CRABP-I between UIA and the control group (p=0.447). The bar represents the standard error of the mean.

• 

  Fig. 3 Potential mechanism between cellular retinoic acid binding protein-I (CRABP-I) and aneurysm rupture. Retinoic acid increases the formation of α-smooth muscle actin (α-SMA) and myosin heavy chain, and the expression of collagen. In contrast, fibronectin and matrix metalloproteinase-2 (MMP-2) are attenuated by retinoic acid. Inhibition of retinoic acid by CRABP-I could attribute to vulnerable aneurysm wall formation in response to hemodynamic stress and may themselves to be more prone to rupture.

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