Doxycycline inhibits matrix metalloproteinase-9 and laminin degradation after transient global cerebral ischemia.
Doxycycline, a tetracycline antibiotic inhibits matrix metalloproteinase (MMP) and reduces neuronal damage in focal brain ischemia. This study was undertaken to assess if doxycycline reduces delayed neuronal damage following transient global cerebral ischemia through MMP inhibition. C57BL/6 mice were subjected to 20 min global cerebral ischemia. Doxycycline was administered to mice 30 min before and 2 h after ischemia. In TUNEL assay, damaged neurons were also apparent in the CA1 and CA2 areas and doxycycline reduced TUNEL-positive neurons. Gelatin gel and in situ zymography showed upregulation of gelatinase activity after ischemia. Doxycycline significantly inhibited MMP-9 activity in gel zymography and also suppressed in situ gelatinase activity. Laminin degradation was remarkable in CA1 and CA2 areas after ischemia and doxycycline reduced the laminin degradation and neuronal loss. Our data suggest that doxycycline may provide a neuroprotection against global cerebral ischemia since it reduces perineuronal laminin degradation by inhibiting MMP-9 activity.
Lee
Hyung
H
Brain Research Institute, Keimyung University, South Korea.
Park
Jong-Wook
JW
Kim
Sang-Pyo
SP
Lo
Eng H
EH
Lee
Seong-Ryong
SR
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002544:Cerebral Infarction / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004318:Doxycycline / Q000494:pharmacology* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D020287:In Situ Nick-End Labeling; D007797:Laminin / Q000187:drug effects* / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D007797:Laminin; D061965:Matrix Metalloproteinase Inhibitors; D018696:Neuroprotective Agents; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; D004318:Doxycycline