Effect of Visible Light on Vasospasticity of Post–Subarachnoid Hemorrhage Cerebrospinal Fluid

Abstract

Cerebral vasospasm (CV) is a serious complication of subarachnoid hemorrhage (SAH) with high morbidity and mortality rates. The mechanism of CV has not been determined. There are many theories related to this unsolved issue, one of which supports CV as a two-stage phenomenon from a pathophysiologic perspective. The first stage consists of inhibition of neuronal nitric oxide synthase by oxyhemoglobin, which results in a decrease of nitric oxide (NO) production. The second stage consists of an increase in the levels of asymmetric dimethylarginine through bilirubin oxidation products (BOXes), which are oxidized by-products of hemoglobin metabolism. These in turn inhibit endothelial nitric oxide synthase (eNOS), which results in the blockage of the second NO production mechanism. BOXes are sensitive to visible light, as is their precursor bilirubin. The hypothesis of CV prevention using the photosensitivity of BOXes was tested in this study. Cerebrospinal fluid (CSF) obtained from two patients with SAH was divided in half and either exposed to a standard dose of visible light or not exposed to any light. The CSF was spectrophotometrically investigated and the concentration of BOXes was measured. A comparison between CSF samples exposed to light and not exposed to light was made. Using two groups of 16 rats each, the vasospastic effect of the CSF exposed and not exposed to light on arteries of the cortical surface was measured. The cortex was exposed using the cranial window. Spectrophotometric analysis revealed that the concentration of BOXes in the CSF decreased significantly after being exposed to visible light ( < 0.001). There was a significant difference of the vasospastic effect of CSF on exposed cortical arteries ( < 0.001). The concentration of BOXes and the vasospastic effect of CSF taken from patients with SAH were significantly reduced after being exposed to visible light if compared with CSF not exposed to light.

Bilirubin Oxidation Products and Cerebral Vasoconstriction

“…Findings support the presence of BOXes in the CSF of SAH patients and, moreover, are associated with CSF from patients symptomatic for vasospasm ( Pyne-Geithman et al, 2005 ; Sabanci et al, 2017 ). Further, it appears that the concentration of BOXes in the CSF of these patients is sufficient to contribute to the vasospasm ( Pyne-Geithman et al, 2005 ; Sabanci et al, 2017 ). Clearly, the concentrations of the different BOXes species and the time courses for their formation remain to be established.…”

“…More recently, constriction of rat arteries in a cranial window preparation in response to CSF (unextracted) from two patients symptomatic for vasospasm was attributed to BOXes based on the (1) absorption of the CSF at 320 nm and (2) decreased constriction of arterioles of rat cortex, determined in a cranial window, following degradation (decreased amount of 320 nm absorption) of BOXes with exposure of the CSF to visible light (380–760 nm, 25 watts and 150 cm distance from sample; Sabanci et al, 2017 ). The attribution of BOXes degradation to the light-induced decrease in CSF-mediated constriction ( Sabanci et al, 2017 ) was based upon earlier findings that ambient (t 1/2 10 h), sun-, and UV light caused decreased absorption of BOX A and BOX B in a reconstituted extract of a hydrogen peroxide–bilirubin reaction mixture ( Kranc et al, 2000 ; Clark et al, 2008b ; Wurster et al, 2008 ). Also, 30 min sunlight exposure isomerized Z -BOX A and Z -BOX B to their respective E regio-isomers and 8 h exposure caused considerable degradation ( Seidel et al, 2015 ).…”