International Journal of Clinical Case Reports, 2025, Vol.15, No.6, 259-270 http://medscipublisher.com/index.php/ijccr 261 2.3 Disruption of the blood-brain barrier and brain injury The integrity of the blood-brain barrier (BBB) is particularly important for maintaining the normal state of the brain, and its damage is a significant feature of brain injury after cardiopulmonary resuscitation. The inflammatory response triggered by restoring blood flow after ischemia can damage the blood-brain barrier, allowing substances harmful to nerves, immune cells and biomarkers in the blood to enter the brain tissue (Jeon et al., 2025). Increased permeability of the blood-brain barrier can aggravate nerve damage, promote immune cells from other parts of the body to enter the brain, and further intensify neuroinflammation and secondary damage (Dou et al., 2023). Through the analysis of single-cell transcriptomics technology, it was found that when the blood-brain barrier is damaged, the cell composition will also change. For example, neutrophils enter the brain and microglia are activated. These changes will trigger inflammatory responses and cause continuous damage (Jiang et al., 2025). Whether the blood-brain barrier is damaged is crucial for the changes in brain injury biomarkers and the interpretation of test results. The molecular weight of S100B is not large. Once the blood-brain barrier is damaged, it can quickly enter the bloodstream. Therefore, it can serve as an early signal of damage to the blood-brain barrier and astrocytes (Kaminoska et al., 2025). The molecular weights of NSE and Nf-L are relatively large. Their contents in the blood will gradually increase over time, which can better reflect the degree of damage to the blood-brain barrier and the continuous damage of nerve cells. Studies show that the predictive effects of these biomarkers are influenced by the integrity of the blood-brain barrier. For instance, when there is moderate to severe damage to the blood-brain barrier, the prediction results of NSE in the blood will be more accurate (Jeon et al., 2024; Jeon et al., 2025). Therefore, clarifying the relationship between the state of the blood-brain barrier and changes in biomarkers is of great significance for accurately interpreting the test results and optimizing the molecular monitoring work after cardiopulmonary resuscitation. 3 Research Progress on Biomarkers of ED Brain Injury after Cardiopulmonary Resuscitation 3.1 Biomarkers of neuronal/glial injury In studies on brain injury after cardiopulmonary resuscitation (CPR), the prognostic role of biomarkers related to neuronal and glial injury has been highlighted. For a long time, neuron-specific enolase (NSE) has been regarded as a reliable indicator for judging the death of nerve cells. High index values lead to poor neurological recovery and a high risk of death, and they will continue to rise within three days after cardiac arrest. The higher the value, the greater the possibility of adverse outcomes (Moseby-Knappe et al., 2021). S100 calcium-binding protein B (S100B) is mainly released by astrocytes and can reflect the damage of neurons and astrocytes, as well as the damage of the blood-brain barrier. Within the first 72 hours after cardiac arrest, an increase in this index is associated with early nerve injury and poor recovery, but its specificity may be affected by injuries in other parts of the body (Hoiland et al., 2022; Kaminoska et al., 2025). Emerging biomarkers such as glial fibrillary acidic protein (GFAP), neurofilament light chain (Nf-L), and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) have shown greater prospects in recent studies. The astrocyte marker GFAP and the Nf-L indicating axonal injury have high sensitivity and specificity in predicting neurological prognosis, and in some studies, they are even superior to traditional markers such as NSE (Mosebe-knappe et al., 2021; Humaloja et al., 2022; Czimmeck et al., 2025). Uk-l1, as a neuronal cell body marker, is also a strong early predictor of poor prognosis. Significant differences can be observed on the first day after sudden arrest (Figure 1) (Hoiland et al., 2022; Kaminoska et al., 2025). The combined measurement of the above markers at appropriate time points is helpful for early risk stratification and guiding clinical decisions in the emergency department. 3.2 Inflammation, oxidative stress and new biomarkers In addition to markers that directly reflect neuronal and glial damage, researchers are now increasingly focusing on inflammation, oxidative stress, and related new molecular mechanisms. After cardiopulmonary resuscitation, patients will experience obvious inflammatory responses throughout their bodies and in their brains. Cytokines such as interleukin-6 (IL-6) and high mobility group protein 1 (HMGB1) are closely related to secondary brain injury and prognosis judgment (Yao et al, 2025). Through proteomics and transcriptomics studies, some candidate
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