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. 2025 Jul 25;17(7):5562-5574.
doi: 10.62347/OTKA7544. eCollection 2025.

Plasma hydrogen sulfide as a promising predictor of collateral cerebral circulation in acute ischemic stroke

Haiyan Chen  1   2   3 , Jianmin Huang  2 , Pin Zheng  4 , Guixin Yang  2 , Bingbing Qin  2 , Mengxue Zang  2 , Jie Wang  5 , Xuebin Li  1   2   3   6
Affiliations

Plasma hydrogen sulfide as a promising predictor of collateral cerebral circulation in acute ischemic stroke

Haiyan Chen et al. Am J Transl Res. .

Abstract

Objectives: To investigate the relationship between plasma hydrogen sulfide (H2S) levels and collateral circulation in patients with acute ischemic stroke (AIS), and to explore the effects of vascular endothelial growth factor (VEGF), homocysteine (Hcy), folic acid (FA), vitamin B12 (VB12), and vitamin B6 (VB6).

Methods: A total of 68 AIS patients were enrolled and classified into two groups based on collateral vessel grading: the Good Collateral Circulation (GCC) group (n = 37) and the Poor Collateral Circulation (PCC) group (n = 31). Plasma levels of H2S, VEGF, Hcy, FA, VB12, and VB6 were measured on the 2nd and 7th days after admission using microassays and ELISA.

Results: Compared to the PCC group, patients in the GCC group had significantly lower National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin Scale scores (mRS) scores at both admission and discharge (all P < 0.05). On both the 2nd and 7th days, plasma levels of H2S, VEGF, FA, VB12, and VB6 were significantly higher in the GCC group, while Hcy levels were significantly lower (all P < 0.05). Within group comparisons between the two time points also showed significant changes (all P < 0.001). Correlation analysis revealed that plasma H2S levels were positively correlated with collateral circulation, VEGF, FA, VB12, and VB6, and negatively correlated with Hcy levels (all P < 0.001). Plasma H2S levels demonstrated high predictive value for collateral circulation (area under the curve, AUC = 0.943). An interaction between time and collateral circulation on H2S levels was also observed.

Conclusions: Plasma H2S levels may serve as a valuable biomarker for predicting good collateral circulation in patients with acute ischemic stroke.

Keywords: Plasma hydrogen sulfide; acute ischemic stroke; collateral circulation; homocysteine; vascular endothelial growth factor.

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Conflict of interest statement

None.

Figures

Figure 1
Figure 1
DSA results of different collateral circulation states. Panels (A-D) show the DSA results on the day after admission for a patient in the PCC group. Panels (A and C): Right middle cerebral artery occlusion (anteroposterior and lateral views). Panels (B and D): The right anterior cerebral artery leptomeningeal vessels compensating for the pericortical blood supply to the ipsilateral middle cerebral artery, with sparse and slow blood flow, and a collateral circulation score of 1 (anteroposterior and lateral views). Panels (E-H) show the DSA results on the day after admission for a patient in the GCC group. Panels (E and G): Right middle cerebral artery occlusion (anteroposterior and lateral views). Panels (F and H): Formation of leptomeningeal vessels and capillary networks from the right external carotid artery and right anterior cerebral artery, compensating for the blood supply to the entire region of the ipsilateral middle cerebral artery, with a collateral circulation score of 4 (anteroposterior and lateral views). DSA, digital subtraction angiography; PCC, poor collateral circulation; GCC, good collateral circulation.
Figure 2
Figure 2
Levels of H2S in peripheral blood in different collateral circulation. Note: Paired t test ###P < 0.001; independent t test, &&&P < 0.001. Plasma hydrogen sulfide (H2S).
Figure 3
Figure 3
Peripheral blood VEGF levels in different collateral circulation. Note: Paired t test ###P < 0.001; independent t test &&&P < 0.001. VEGF, vascular endothelial growth factor.
Figure 4
Figure 4
Levels of Hcy, FA, VB6 and VB12 in peripheral blood in different collateral circulation. Note: Paired t test ###P < 0.001; independent t test &&&P < 0.001. Hcy, homocysteine; VB6, vitamin B6; FA, folic acid; VB12, vitamin B12.
Figure 5
Figure 5
ROC curve of H2S expression on collateral circulation. ROC, receiver operator characteristic curve; AUC, Area Under The Curve. Plasma hydrogen sulfide (H2S).
Figure 6
Figure 6
Interaction of time and collateral circulation on H2S change. Plasma hydrogen sulfide (H2S).
See this image and copyright information in PMC

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