International Journal of Clinical Case Reports, 2025, Vol.15, No.6, 259-270 http://medscipublisher.com/index.php/ijccr 262 molecules related to neurodegeneration and inflammatory responses have also been discovered, such as Lipocalin-2. Among them, Lipocalin-2 has received particular attention and has become a novel biomarker for judging the early recovery of the nervous system. Experiments have also proved that it is associated with nerve cell death caused by brain injury after cardiac arrest (Yao et al., 2025). Figure 1 TheNeurovascularUnitandBrainInjuryBiomarkerRelease (Adopted from Hoiland et al., 2022) The latest research has explored the value of brain-derived extracellular vesicles and small molecule Rnas as serum markers of brain injury. These molecules are derived from damaged nerve cells and glial cells and can be detected in the blood within a few hours after resuscitation, providing new information that traditional protein markers do not have (Ghaith et al., 2022). For instance, micrornas (like miR-124) in extracellular vesicles derived from nerve cells were detected within 6 hours after cardiac arrest, and the results were closely related to neural recovery (Shen et al., 2023). These new markers are still in the early stages of clinical application, but they are expected to make the assessment of brain injury in emergency situations more timely and accurate in the future. 3.3 Multi-marker prognostic assessment model Because brain injuries after cardiopulmonary resuscitation are complex and diverse, it is difficult to comprehensively reflect the degree of injury with only one biomarker, and the accuracy of predicting prognosis is also insufficient. Therefore, evaluation models that incorporate multiple biomarkers have received extensive attention. This model integrates multiple biomarkers with clinical data, electrophysiological examinations, and imaging results to achieve better predictive effects. Studies have found that the combination of markers such as NSE, GFAP, and protein gene product 9.5 (PGP 9.5) can significantly improve the effect of neurological prognosis assessment. The area under the curve (AUC) for predicting poor prognosis in some marker combinations can exceed 0.94 (Hang et al., 2025). Adding neurofilament light chain (Nf-L) to the existing prognosis assessment methods can also improve the sensitivity of predicting poor prognosis and identify those patients that might be missed by traditional methods (Janas et al., 2025; Czimmeck et al., 2025). The latest guidelines propose that multimodal prediction strategies should combine clinical examinations, biomarkers, electrophysiological examinations and neuroimaging, which can make decisions more reasonable and reduce judgment errors (Bang et al., 2024). Compared with models relying solely on clinical indicators, prognostic models incorporating novel neurobiomarkers such as UCH-L1 have better predictive effects, higher area under the receiver operating characteristic curve (AUC), and improved accuracy, sensitivity, and specificity (Ding et al., 2024). These advancements indicate that it is necessary for emergency departments to adopt this comprehensive and multimodal neuroprognosis assessment strategy-by fully leveraging the advantages of multiple biomarkers and diagnostic methods, it can better guide the treatment after cardiopulmonary resuscitation and enable patients to recover better.
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