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Hypoxic hypoperfusion in acute and chronic ischemia induces hypoxia-inducible factor-1α (HIF-1α), which induces the fur gene to transcribe the convertase, furin. Activation of proMMP-14 (membrane-type MMP) is necessary for the activation of proMMP-2, which attacks the tight junction proteins and basal lamina opening the blood–brain barrier (BBB). As a consequence of the activation of the MMPs, myelin is broken down. MMP, matrix metalloproteinases.
