title: Dexamethasone inhibits ICAM-1 and MMP-9 expression and reduces brain edema in intracerebral hemorrhagic rats.
abstract: BACKGROUND
  The molecular mechanism of hemorrhagic stroke is unclear, and the identification of therapeutic agents for attenuating post-stroke brain damage remains an unresolved challenge. Dexamethasone (DEX) is used clinically to treat spinal cord injury and brain tumor patients by reducing edema formation, but has produced conflicting results in stroke management.
  
  
  METHODS
  In this study, intracerebral hemorrhage (ICH) was induced in rats by intracranial stereotactic injection of collagenase into the caudate nucleus. DEX was given immediately and 3 days after ICH. The expression of intercellular adhesion molecule-1 (ICAM-1), matrix metalloproteinase-9 (MMP-9), nuclear factor (NF)-κB, and IκB were analyzed by Western blotting, and perihematomal edema formation was evaluated by magnetic resonance imaging.
  
  
  RESULTS
  The results showed that ICH caused an increase of ICAM-1 and MMP-9 expression from 4 h to 7 days, which was inhibited following the administration of DEX. The perihematomal edema volume in ICH rats was high, with two peak periods at 12 h and 3 days, which was also reduced in DEX-treated groups. Furthermore, the administration of DEX not only maintained IκB in cytoplasm, but also decreased NF-κB elevation in the nucleus at 3 and 5 days in ICH rats.
  
  
  CONCLUSIONS
  In conclusion, these data show that DEX successfully reduced post-stroke brain edema by decreasing MMP-9 and ICAM-1 levels, partially through the IκB/NF-κB signaling pathway. The timing of DEX administration in relation to the onset of brain injury may be critical.
authors.affiliation: Department of Neurosurgery, Chang Gung Memorial Hospital at Chia-Yi, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan. jents716@ms32.hinet.net
authors.forename: Jen-Tsung
authors.initials: JT
authors.lastname: Yang
authors.forename: Tsong-Hai
authors.initials: TH
authors.lastname: Lee
authors.forename: I-Neng
authors.initials: IN
authors.lastname: Lee
authors.forename: Chiu-Yen
authors.initials: CY
authors.lastname: Chung
authors.forename: Chia-Hui
authors.initials: CH
authors.lastname: Kuo
authors.forename: Hsu-Huei
authors.initials: HH
authors.lastname: Weng
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism*; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D018799:Intercellular Adhesion Molecule-1; D003907:Dexamethasone; D020780:Matrix Metalloproteinase 9