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Cerebral ischemia is caused by perturbations in blood flow to the brain that trigger sequential and complex metabolic and cellular pathologies. This leads to brain tissue damage, including neuronal cell death and cerebral infarction, manifesting clinically as ischemic stroke, which is the cause of considerable morbidity and mortality worldwide. To analyze the underlying biological mechanisms and identify potential biomarkers of ischemic stroke, various in vitro and in vivo experimental models have been established investigating different molecular aspects, such as genes, microRNAs, and proteins. Yet, the metabolic and cellular pathologies of ischemic brain injury remain not fully elucidated, and the relationships among various pathological mechanisms are difficult to establish due to the heterogeneity and complexity of the disease. Metabolome-based techniques can provide clues about the cellular pathologic status of a condition as metabolic disturbances can represent an endpoint in biological phenomena. A number of investigations have analyzed metabolic changes in samples from cerebral ischemia patients and from various in vivo and in vitro models. We previously analyzed levels of amino acids and organic acids, as well as polyamine distribution in an in vivo rat model, and identified relationships between metabolic changes and cellular functions through bioinformatics tools. This review focuses on the metabolic and cellular changes in cerebral ischemia that offer a deeper understanding of the pathology underlying ischemic strokes and contribute to the development of new diagnostic and therapeutic approaches.

ObjectiveThis study was conducted to evaluate a problem-oriented focused torso bedside ultrasound protocol termed “Sonographic Evaluation of Aetiology for Respiratory difficulty, Chest pain, and/or Hypotension” (SEARCH 8Es) for its ability to narrow differential diagnoses and increase physicians’ diagnostic confidence, and its diagnostic accuracy, for patients presenting with dyspnea, chest pain, or symptomatic hypotension.MethodsThis single-center prospective observational study was conducted over 12 months in an emergency department and included 308 patients (184 men and 124 women; mean age, 67.7 ± 19.1 years) with emergent cardiopulmonary symptoms. The paired t-test was used to compare the number of differential diagnoses and physician’s level of confidence before and after SEARCH 8Es. The overall accuracy of the SEARCH 8Es protocol in differentiating 13 diagnostic entities was evaluated based on concordance (kappa coefficient) with the diagnosis made by the inpatient specialists. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated.ResultsSEARCH 8Es narrows the number of differential diagnoses (2.5 ± 1.5 vs. 1.4 ± 0.7; p < 0.001) and improves physicians’ diagnostic confidence (2.8 ± 0.8 vs. 4.3 ± 0.9; p < 0.001) significantly. The overall kappa coefficient value was 0.870 (p < 0.001), with the overall sensitivity, specificity, positive predictive value, and negative predictive value at 90.9%, 99.0%, 89.7%, and 99.0%, respectively.ConclusionThe SEARCH 8Es protocol helps emergency physicians to narrow the differential diagnoses, increase diagnostic confidence and provide accurate assessment of patients with dyspnea, chest pain, or symptomatic hypotension.

Clinical Trial Registry of Korea: https://cris.nih.go.kr/cris/index.jsp KCT0001937.