Soluble receptor for advanced glycation end products as a biomarker of symptomatic vasospasm in subarachnoid hemorrhage

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The receptor for advanced glycation end products (RAGE) is a membrane protein associated with the induction of oxidative stress and inflammation in several pathological conditions. Previous studies have demonstrated that soluble RAGE (sRAGE) acts as a decoy for RAGE and protects cells against RAGE-mediated injury. The authors and other groups have reported that the expression of RAGE increases after brain ischemia and subarachnoid hemorrhage (SAH), and deletion of RAGE or overexpression of sRAGE improves neuronal survival. It has also been demonstrated that the plasma sRAGE level could be a predictor of the outcome after ischemic stroke. This study aimed to evaluate plasma sRAGE as a biomarker for symptomatic vasospasm (SVS) in SAH patients, as well as a rat model.


The authors measured and compared plasma sRAGE levels in 27 SAH patients (7 with SVS and 20 without SVS) from day 5 to day 14 post-SAH. They also examined plasma sRAGE levels and expression of RAGE and heme oxygenase–1 (HO-1) in a rat SAH model.


The relative plasma sRAGE levels were significantly lower in the SVS group than in the non-SVS group of patients. A cut-off value of 0.84 for predicting SVS was considered to be appropriate for the relative plasma sRAGE levels on day 7 versus day 5. In the rat SAH model, plasma sRAGE levels were significantly lower than those in sham-treated rats, and the expressions of RAGE and HO-1 were enhanced in the SAH group compared with the non-SAH group.


Plasma sRAGE levels can be used as a potential biomarker for predicting SVS after SAH.

ABBREVIATIONS ACA = anterior cerebral artery; AGE = advanced glycation end product; cRAGE = cleaved RAGE; ELISA = enzyme-linked immunosorbent assay; esRAGE = endogenous secretory RAGE; HO-1 = heme oxygenase–1; ICA = internal carotid artery; MCA = middle cerebral artery; qRT-PCR = quantitative reverse-transcription polymerase chain reaction; RAGE = receptor for advanced glycation end products; ROC = receiver operating characteristic; SAH = subarachnoid hemorrhage; sRAGE = soluble RAGE; SVS = symptomatic vasospasm; VS = vasospasm.

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Contributor Notes

Correspondence Osamu Hori: Kanazawa University, Ishikawa, Japan. WHEN CITING Published online November 1, 2019; DOI: 10.3171/2019.8.JNS191269.Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.


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