Treatment of cold injury-induced brain edema with a nonspecific matrix metalloproteinase inhibitor MMI270 in rats.
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 MMI270-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.
Kawai
N
N
Department of Neurological Surgery, Kagawa Medical University, Kagawa, Japan. nobu@kms.ac.jp
Kawanishi
M
M
Nagao
S
S
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D001929:Brain Edema / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D001930:Brain Injuries / Q000150:complications* / Q000209:etiology / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects; D003080:Cold Temperature; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D010296:Parietal Lobe / Q000473:pathology; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling; D013449:Sulfonamides / Q000494:pharmacology*
C097658:CGS 27023A; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D011719:Pyrazines; D013449:Sulfonamides