Doxycycline inhibits matrix metalloproteinase-9 and laminin degradation after transient global cerebral ischemia

Hyung Lee; Jong-Wook Park; Sang-Pyo Kim; Eng H. Lo; Seong-Ryong Lee

Neurobiology of Disease (May 2009)

Doxycycline inhibits matrix metalloproteinase-9 and laminin degradation after transient global cerebral ischemia

Hyung Lee,
Jong-Wook Park,
Sang-Pyo Kim,
Eng H. Lo,
Seong-Ryong Lee

Affiliations

Hyung Lee: Brain Research Institute, Keimyung University, 700-712, South Korea
Jong-Wook Park: Chronic Disease Research Center, Keimyung University, School of Medicine, Taegu 700-712, South Korea
Sang-Pyo Kim: Brain Research Institute, Keimyung University, 700-712, South Korea
Eng H. Lo: Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Seong-Ryong Lee: Brain Research Institute, Keimyung University, 700-712, South Korea; Department of Pharmacology, School of Medicine, Keimyung University, 194 Dongsan dong, Junggu, Taegu 700-712, South Korea; Chronic Disease Research Center, Keimyung University, School of Medicine, Taegu 700-712, South Korea; Corresponding author. Department of Pharmacology, School of Medicine, Keimyung University, 194 Dongsan dong, Junggu, Taegu 700-712, South Korea. Fax: +82 53 250 7016.

Journal volume & issue: Vol. 34, no. 2
pp. 189 – 198

Abstract

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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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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