The MAPK-ERK1/2 signaling pathway has been demonstrated to modulate the expression of TJ proteins and alter the molecular composition within TJ proteins complexes [50], e.g. activation of ERK1/2 leads to increased ZO-1 degradation during traumatic brain injury [51], decreased ZO-1 and Claudin-5 expression in brain endothelium during HIV infection [52, 53], and reduced Occludin and Claudin-5 expression in BBB endothelium during ischemic stroke [54]. This evidence concerns the gene CLDN5 and ischemic stroke.