Abstract
Blood-brain barrier (BBB) disruption is a critical event leading to vasogenic brain edema and secondary brain damage after cold injury-induced brain trauma. Matrix metalloproteinases (MMPs) are implicated in BBB disruption in this model. The purpose of this study was to examine the effects of MMI270, a synthetic nonspecific MMP inhibitor, on cold injury-induced brain edema in rats. Treatment with MMI270, a bolus injection at a dose of 30 mg/kg, was started immediately after the induction of cold injury and was continued at a dose of 40 mg/kg/day using an intraperitoneal osmotic minipump. At 24 hours after the cold injury, the brain water content and the BBB permeability to Evans Blue (EB) were determined. The secondary brain lesion was assessed using hematoxylin and eosin (H-E) staining at 7 days after the cold injury. Compared with the untreated control group, treatment with MMI270 significantly reduced the brain water content in the ipsilateral core and intermediate areas and protected the BBB integrity to EB in the ipsilateral core area. The secondary lesion was significantly smaller in the MM1270-treated animals compared with the untreated animals. Our results indicate that treatment with MMI270 in rats exhibits protection in acute brain edema formation and secondary brain lesion by attenuating the BBB permeability after cold injury.
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References
Asahi M, Asahi K, Jung J-C, del Zoppo GJ, Fini ME, Lo EH (2000) Role for matrix metalloproteinase 9 after focal cerebral ischemia: effects of gene knockout and enzyme inhibition with BB-94. J Cereb Blood Flow Metab 20: 1681–1689
Gasche Y, Fujimura M, Morita-Fujimura Y, Copin J-C, Kawase M, Massengale J, Chan PH (1999) Early appearance of activated matrix metalloproteinase-9 after focal cerebral ischemia in mice: a possible role in blood-brain barrier dysfunction. J Cereb Blood Flow Metab 19: 1020–1028
Morita-Fujimura Y, Fujimura M, Gasche Y, Copin J-C, Chan PH (2000) Overexpression of zinc superoxide dismutase in transgenic mice prevents the induction and activation of matrix metalloproteinase after cold injury-induced brain trauma. J Cereb Blood Flow Metab 20: 130–138
Murakami K, Kondo T, Yang G, Chen SF, Morita-Fujimura Y, Chan PH (1999) Cold injury in mice: a model of to study mechanism of brain edema and neuronal apoptosis. Prog Neurobiol 57: 289–299
Romanic AM, White RF, Arleth AJ, Ohlstein EH, Barone FC (1998) Matrix metalloproteinase expression increases after cerebral focal ischemia in rats: inhibition of matrix metalloproteinase-9 reduces infarct size. Stroke 29: 1020–1030
Rosenberg GA, Estrada EY, Dencoff JE (1998) Matrix metalloproteinase and TIMPs are associated with blood-brain barrier opening after reperfusion in rat brain. Stroke 29: 2189–2195
Rosenberg GA, Navratil M, Barone F, Feuerstein G (1996) Proteolytic cascade enzymes increase in focal cerebral ischemia in rat. J Cereb Blood Flow Metab 16: 360–366
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© 2003 Springer-Verlag Wien
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Kawai, N., Kawanishi, M., Nagao, S. (2003). Treatment of cold injury-induced brain edema with a nonspecific matrix metalloproteinase inhibitor MMI270 in rats. In: Kuroiwa, T., et al. Brain Edema XII. Acta Neurochirurgica Supplements, vol 86. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0651-8_63
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DOI: https://doi.org/10.1007/978-3-7091-0651-8_63
Publisher Name: Springer, Vienna
Print ISBN: 978-3-7091-7220-9
Online ISBN: 978-3-7091-0651-8
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