title: Melatonin reduced the elevated matrix metalloproteinase-9 level in a rat photothrombotic stroke model.
abstract: BACKGROUND
  The accumulation of toxic free radicals plays a pivotal role in the early molecular cascades of blood-brain barrier (BBB) disruption mediated by matrix metalloproteinases (MMPs) activation in ischemic stroke. Theoretically, it is expected that early blockade of activation of MMPs may provide protective effects from secondary neural tissue damage. The present study was designed to determine the ability of melatonin to influence MMP-9 activity and BBB disruption, in a focal ischemia rat model induced by photothrombosis.
  
  
  METHODS
  Adult, male, 8-week Sprague-Dawley rats weighing 230-300 g received focal cerebral ischemia by photothrombosis using Rose Bengal (RB). The injured animals were divided into two groups. One group received 50mg/kg of melatonin intraperitoneally, starting 1h after injury and at 12h intervals for 3 days. The control group received weight-adjusted doses of saline vehicle. In each group, MMP-9 expression and activity were assessed by Western blot and gelatin zymography, respectively, at various times. The effects of melatonin on BBB disruption and brain edema were also determined.
  
  
  RESULTS
  MMP-9 activity and expression were significantly elevated at 24h in the ischemic cortex, which remained up-regulated at least until 72 h after injury. Melatonin treatment significantly attenuated MMP-9 activity and expression at 24, 48, and 72 h after ischemic injury. Relative to control group, BBB permeability was significantly reduced in the melatonin-treated group. The water content was decreased by melatonin treatment, although there was no statistically significant difference.
  
  
  CONCLUSIONS
  Melatonin treatment starting 1h after injury attenuated BBB disruption during focal ischemia, which is at least partly due to inhibition of MMP-9 activity. Melatonin might have a potential role in clinical trials aimed to improve the outcome of patients suffering cerebral ischemia.
authors.affiliation: Department of Neurosurgery, Chonnam National University Medical School & Research Institute of Medical Sciences, Gwangju, Republic of Korea.
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Jang
authors.forename: Jung-Kil
authors.initials: JK
authors.lastname: Lee
authors.forename: Min-Cheol
authors.initials: MC
authors.lastname: Lee
authors.forename: Min-Sheng
authors.initials: MS
authors.lastname: Piao
authors.forename: Soo-Han
authors.initials: SH
authors.lastname: Kim
authors.forename: Hyung-Seok
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001834:Body Water; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D002545:Brain Ischemia / Q000188:drug therapy / Q000201:enzymology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D004789:Enzyme Activation / Q000187:drug effects; D007274:Injections, Intraperitoneal; D020767:Intracranial Thrombosis / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects*; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D010777:Photochemistry; D016548:Prosencephalon / Q000201:enzymology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012395:Rose Bengal / Q000528:radiation effects / Q000633:toxicity
chemical_list: D012395:Rose Bengal; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; D008550:Melatonin