A thrombin inhibitor reduces brain edema, glioma mass and neurological deficits in a rat glioma model.
Although thrombin is a critical enzyme in the coagulation cascade, it has become apparent that it has many other effects. Thus, it may induce brain edema formation, angiogenesis and cell proliferation. Because of the importance of these three factors in the extremely poor prognosis of glioma patients, the present study examined the role of thrombin in that disease state. We found that thrombin activity is increased in a rat glioma model and thrombin positive cells were present in the tumor. Anti-thrombin treatment with argatroban reduced brain edema, tumor growth, and tumor-related neurological deficits. Our results suggest that thrombin is a new target for glioma treatment.
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Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan 48109-0532, USA. yahua@umich.edu
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D000818:Animals; D000991:Antithrombins / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives; D001929:Brain Edema / Q000209:etiology / Q000473:pathology*; D001932:Brain Neoplasms / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D005910:Glioma / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D009422:Nervous System Diseases / Q000209:etiology / Q000503:physiopathology*; D010875:Pipecolic Acids / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013449:Sulfonamides; D013917:Thrombin / Q000378:metabolism
D000991:Antithrombins; D010875:Pipecolic Acids; D013449:Sulfonamides; D001120:Arginine; D013917:Thrombin; C031942:argatroban