Potential Biomarkers in Serum for Ischemic Stroke
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Early detection of ischemic stroke is essential for initiating treatment before irreversible braininjury occurs. This study aimed to identify novel serum biomarkers capable of detectingischemic stroke in early stages, prior to the development of severe brain damage caused bycerebral artery occlusion. Male Sprague-Dawley rats (9 weeks old; n= 3 per group) underwentmiddle cerebral artery occlusion for 0 minutes (sham), 30 minutes (0.5 hour), 1 hour, 2 hours,or 3 hours. Next-generation sequencing of brain tissue identified integrin subunit alpha M(Itgam ; CD11B), C-C motif chemokine ligand 2 (Ccl2), and alpha-2-macroglobulin (A2m)as candidate biomarkers. Western blot validation analysis revealed that CD11B and CCL2levels progressively increased in both brain tissue and serum, correlating with occlusionduration and the extent of brain damage. In contrast, A2M expression decreased in braintissue but increased in serum with longer occlusion times. Notably, in the 0.5 hour occlusiongroup, no visible brain damage was observed by 2,3,5-triphenyltetrazolium chloride staining;however, serum levels of CCL2 and A2M were significantly elevated compared to the shamgroup. These findings suggest that CD11B, CCL2, and A2M are promising early biomarkersfor ischemic stroke. Increases in their serum concentrations occur at the earliest stagesof ischemia, potentially enabling early diagnosis and therapeutic intervention beforeirreversible brain damage becomes detectable by conventional imaging techniques.
Abstract
Early detection of ischemic stroke is essential for initiating treatment before irreversible braininjury occurs. This study aimed to identify novel serum biomarkers capable of detectingischemic stroke in early stages, prior to the development of severe brain damage caused bycerebral artery occlusion. Male Sprague-Dawley rats (9 weeks old; n= 3 per group) underwentmiddle cerebral artery occlusion for 0 minutes (sham), 30 minutes (0.5 hour), 1 hour, 2 hours,or 3 hours. Next-generation sequencing of brain tissue identified integrin subunit alpha M(Itgam ; CD11B), C-C motif chemokine ligand 2 (Ccl2), and alpha-2-macroglobulin (A2m)as candidate biomarkers. Western blot validation analysis revealed that CD11B and CCL2levels progressively increased in both brain tissue and serum, correlating with occlusionduration and the extent of brain damage. In contrast, A2M expression decreased in braintissue but increased in serum with longer occlusion times. Notably, in the 0.5 hour occlusiongroup, no visible brain damage was observed by 2,3,5-triphenyltetrazolium chloride staining;however, serum levels of CCL2 and A2M were significantly elevated compared to the shamgroup. These findings suggest that CD11B, CCL2, and A2M are promising early biomarkersfor ischemic stroke. Increases in their serum concentrations occur at the earliest stagesof ischemia, potentially enabling early diagnosis and therapeutic intervention beforeirreversible brain damage becomes detectable by conventional imaging techniques.