title: Contribution of matrix metalloproteinase-9 to cerebral edema and functional outcome following experimental subarachnoid hemorrhage.
abstract: BACKGROUND
  Cerebral edema is an important risk factor for death and poor outcome following subarachnoid hemorrhage (SAH). However, underlying mechanisms are still poorly understood. Matrix metalloproteinase (MMP)-9 is held responsible for the degradation of microvascular basal lamina proteins leading to blood-brain barrier dysfunction and, thus, formation of vasogenic cerebral edema. The current study was conducted to clarify the role of MMP-9 for the development of cerebral edema and for functional outcome after SAH.
  
  
  METHODS
  SAH was induced in FVB/N wild-type (WT) or MMP-9 knockout (MMP-9(-/-)) mice by endovascular puncture. Intracranial pressure (ICP), regional cerebral blood flow (rCBF), and mean arterial blood pressure (MABP) were continuously monitored up to 30 min after SAH. Mortality was quantified for 7 days after SAH. In an additional series neurological function and body weight were assessed for 3 days after SAH. Subsequently, ICP and brain water content were quantified.
  
  
  RESULTS
  Acute ICP, rCBF, and MABP did not differ between WT and MMP-9(-/-) mice, while 7 days' mortality was lower in MMP-9(-/-) mice (p = 0.03; 20 vs. 60%). MMP-9(-/-) mice also exhibited better neurological recovery, less brain edema formation, and lower chronic ICP.
  
  
  CONCLUSIONS
  The results of the current study suggest that MMP-9 contributes to the development of early brain damage after SAH by promoting cerebral edema formation. Hence, MMP- 9 may represent a novel molecular target for the treatment of SAH.
authors.affiliation: Department of Neurosurgery, University of Munich, Medical Center Grosshadern, Ludwig Maximilians University, Munich, Germany.
authors.forename: Sergej
authors.initials: S
authors.lastname: Feiler
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Plesnila
authors.forename: Serge C
authors.initials: SC
authors.lastname: Thal
authors.forename: Stefan
authors.initials: S
authors.lastname: Zausinger
authors.forename: Karsten
authors.initials: K
authors.lastname: Schöller
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001794:Blood Pressure; D001835:Body Weight; D001929:Brain Edema / Q000201:enzymology / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control; D002560:Cerebrovascular Circulation; D003243:Consciousness; D005260:Female; D007427:Intracranial Pressure; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity; D012018:Reflex; D012039:Regional Blood Flow; D012677:Sensation; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D013997:Time Factors
chemical_list: D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse