title: 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.
authors.affiliation: Stroke Clinical Research Unit, Department of Neurology, West China Hospital, Sichuan University, 610041 Chengdu, PR China. leichunyan328@163.com
authors.forename: C
authors.initials: C
authors.lastname: Lei
authors.forename: S
authors.initials: S
authors.lastname: Lin
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.forename: W
authors.initials: W
authors.lastname: Tao
authors.forename: W
authors.initials: W
authors.lastname: Dong
authors.forename: Z
authors.initials: Z
authors.lastname: Hao
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.forename: B
authors.initials: B
authors.lastname: Wu
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D017364:Collagenases / Q000633:toxicity; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D034741:RNA, Small Interfering / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*; D012720:Severity of Illness Index; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D020932:Nerve Growth Factor; D017364:Collagenases; D020780:Matrix Metalloproteinase 9; D001973:Bromodeoxyuridine