Therefore, it’s plausible that systemic inflammation in critically ill patients leads to elevation of soluble factors disrupting the BBB integrity (e.g. VEGF-A, CXCL13), a first hit followed by the recruitment of inflammatory cells by chemokines (e.g. CXCL13/CXCR5 and CXCL1/CXCR2 axis), causing neuronal injury and acute cognitive failure that manifests as delirium. Here, CXCL1 is linked to delirium.