Activation of cerebral recovery by matrix metalloproteinase-9 after intracerebral hemorrhage

Abstract

Cerebral ischemia, traumatic brain injury, intracerebral hemorrhage and other brain insults trigger neurogenesis in the subventricular zone and hippocampal subgranular zone, and newly formed blood vessels promote the migration of these new neuronal cells to damaged brain regions. The molecular steps involved in brain injury-induced angiogenesis and neurogenesis are unclear. Here we used a rat model of collagenase-induced intracerebral hemorrhage (ICH) to examine whether matrix metalloproteinase-9 (MMP-9), a zinc endopeptidase that regulates growth factor levels during recovery from brain injury, is involved in neurogenesis and angiogenesis following ICH. Induction of ICH led to significant increases in the levels of MMP-9, vascular endothelial growth factor (VEGF), and nerve growth factor (NGF), as well as in the numbers of 5-bromo-2-deoxyuridine (BrdU)- and doublecortin (DCX)-positive cells, in the ipsilateral brain. Intracerebroventricular injection of MMP-9 siRNA reduced these ICH-induced increases. These findings suggest that MMP-9 may promote angiogenesis and neurogenesis during recovery from ICH.