Subarachnoid Hemorrhage Increases Level of Heme Oxygenase-1 and Biliverdin Reductase in the Choroid Plexus

Abstract

Subarachnoid hemorrhage is a specific, life-threatening form of hemorrhagic stroke linked to high morbidity and mortality. It has been found that the choroid plexus of the brain ventricles forming the blood-cerebrospinal fluid barrier plays an important role in subarachnoid hemorrhage pathophysiology. Heme oxygenase-1 and biliverdin reductase are two of the key enzymes of the hemoglobin degradation cascade. Therefore, the aim of present study was to investigate changes in protein levels of heme oxygenase-1 and biliverdin reductase in the rat choroid plexus after experimental subarachnoid hemorrhage induced by injection of non-heparinized autologous blood to the cisterna magna. Artificial cerebrospinal fluid of the same volume as autologous blood was injected to mimic increased intracranial pressure in control rats. Immunohistochemical and Western blot analyses were used to monitor changes in the of heme oxygenase-1 and biliverdin reductase levels in the rat choroid plexus after induction of subarachnoid hemorrhage or artificial cerebrospinal fluid application for 1, 3, and 7 days. We found increased levels of heme oxygenase-1 and biliverdin reductase protein in the choroid plexus over the entire period following subarachnoid hemorrhage induction. The level of heme oxygenase-1 was the highest early (1 and 3 days) after subarachnoid hemorrhage indicating its importance in hemoglobin degradation. Increased levels of heme oxygenase-1 were also observed in the choroid plexus epithelial cells at all time points after application of artificial cerebrospinal fluid. Biliverdin reductase protein was detected mainly in the choroid plexus epithelial cells, with levels gradually increasing during subarachnoid hemorrhage. Our results suggest that heme oxygenase-1 and biliverdin reductase are involved not only in hemoglobin degradation but probably also in protecting choroid plexus epithelial cells and the blood-cerebrospinal fluid barrier from the negative effects of subarachnoid hemorrhage.

Relationship between astrocyte damage and different levels of cerebrospinal fluid markers and prognosis in patients with subarachnoid hemorrhage

“…Cerebral vasospasm is an important complication of SAH, and the two important candidates for causing cerebral arterial spasm are the red blood cell product HbO 2 and the vasoconstrictor ET. Some scholars have found [15] that the combination of HbO 2 and ET activates diffusion neurons in the cerebral cortex in vivo, and suggests the nitric oxide scavenging function of HbO 2 . When the availability of nitric oxide decreases, the threshold concentration of ET induced cerebral ischemia significantly decreases through the complex interaction between the neuronal astrocyte network In general, astrocyte damage in SAH patients was positively correlated with the content of ACKR3, Cx43, HbO 2 , and ET in cerebrospinal fluid.…”

Modulation of Cerebrospinal Fluid Dysregulation via a SPAK and OSR1 Targeted Framework Nucleic Acid in Hydrocephalus

“…[41] Previous studies have revealed that inflammation can disrupt the integrity of ChP barriers, leading to the accumulation of immune cells. [57][58][59] In this study, we employed ZO-1, a classical tight junction protein, as an indicator of blood-CSF barrier integrity in PHH. The results revealed a disrupted ZO-1 staining pattern in the choroid plexus of PHH.…”