Abstract
BackgroundRed blood cell-induced cerebral inflammation and toxicity has been shown to be attenuated by induction of the heme-catalyzing enzyme, hemoxygenase-1 (HO-1), in animal models of subarachnoid hemorrhage (SAH). Although inflammatory mechanisms leading to secondary neuronal injury in SAH are becoming increasingly well understood, markers of cerebral inflammation have so far not been implemented in clinical prediction models of SAH.MethodsIn this biomarker observational study, HO-1 messenger ribonucleic acid (mRNA) expression levels were determined in cerebrospinal fluid (CSF) and blood of 66 patients with aneurysmal SAH on days 1, 7, and 14 after the SAH event. HO-1 mRNA expression was determined via real time polymerase chain reaction (PCR), and relative expression changes were quantified in comparison with expression levels in nonhemorrhagic control CSF. Subarachnoid blood burden, as well as presence of vasospasm and delayed cerebral ischemia (DCI), were recorded. Short and long-term clinical outcomes were assessed using the Modified Rankin Scale at discharge and 1 year after the SAH event.ResultsCSF HO-1 expression levels showed a significant increase over the 14-day observation period (p < 0.001, F = 22.53) and correlated with intracranial hematoma burden (ρ = 0.349, p = 0.025). In multivariate analyses, CSF HO-1 expression levels did not reach significance as independent predictors of outcome. Vasospasm on computed tomographic angiography was associated with lower CSF HO-1 expression levels on day 7 after SAH (n = 53, p = 0.010), whereas patients with DCI showed higher CSF HO-1 expression levels on day 14 after SAH (n = 21, p = 0.009).ConclusionsHO-1 expression in CSF in patients with SAH follows a distinct temporal induction pattern and is dependent on intracranial hematoma burden. CSF HO-1 expression was unable to predict functional outcome. Associations of early low HO-1 expression with vasospasm and late elevated HO-1 expression with DCI may point to detrimental effects of late HO-1 induction, warranting the need for further investigation in a larger study population.
Highlights
Aneurysmal subarachnoid hemorrhage (SAH) continues to be associated with high mortality and persisting disability rates [1], even more so in poor-grade SAH (Hunt & Hess or World Federation of Neurosurgical Societies [WFNS] grades 4 and 5) [2]
cerebrospinal fluid (CSF) hemoxygenase enzymes (HO)‐1 messenger ribonucleic acid (mRNA) Expression Levels Increase After SAH CSF HO-1 mRNA expression levels exhibited a significant increase during the 14-day time course of observation, indicating HO-1 induction that markedly
In this single-center biomarker observational study, we confirmed that HO-1 mRNA expression levels in the CSF of patients with SAH correlate with intracranial hematoma size
Summary
Aneurysmal subarachnoid hemorrhage (SAH) continues to be associated with high mortality and persisting disability rates [1], even more so in poor-grade SAH (Hunt & Hess or World Federation of Neurosurgical Societies [WFNS] grades 4 and 5) [2]. Red blood cell-induced cerebral inflammation and toxicity has been shown to be attenuated by induc‐ tion of the heme-catalyzing enzyme, hemoxygenase-1 (HO-1), in animal models of subarachnoid hemorrhage (SAH). Methods: In this biomarker observational study, HO-1 messenger ribonucleic acid (mRNA) expression levels were determined in cerebrospinal fluid (CSF) and blood of 66 patients with aneurysmal SAH on days 1, 7, and 14 after the SAH event. Results: CSF HO-1 expression levels showed a significant increase over the 14-day observation period (p < 0.001, F = 22.53) and correlated with intracranial hematoma burden (ρ = 0.349, p = 0.025). Conclusions: HO-1 expression in CSF in patients with SAH follows a distinct temporal induction pattern and is dependent on intracranial hematoma burden.
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