Serine protease inhibitor attenuates intracerebral hemorrhage-induced brain injury and edema formation in rat.
Our previous studies have demonstrated that thrombin plays an important role in intracerebral hemorrhage (ICH)-induced brain injury and edema formation. We, therefore, examined whether nafamostat mesilate (FUT), a serine protease inhibitor, can reduce ICH-induced brain injury. Anesthetized male Sprague-Dawley rats received an infusion of autologous whole blood (100 microL), thrombin (5U/50 microL) or type VII collagenase (0.4 U/2 microL) into the right basal ganglia, the three ICH models used in the present study. FUT (10 mg/kg) or vehicle was administered intraperitoneally 6 h after ICH (or immediately after thrombin infusion) and then at 12-h intervals (six treatments in total, n = 5 in each group). All rats were sacrificed 72 h later. We also examined whether FUT promotes rebleeding in a model in which ICH was induced by intracerebral injection of collagenase. Systemic administration of FUT starting 6 h after ICH reduced brain water content in the ipsilateral basal ganglia 72 h after ICH compared with vehicle. FUT attenuated ICH-induced changes in 8-OHdG and thrombin-reduced brain edema. FUT did not increase collagenase-induced hematoma volume. FUT attenuates ICH-induced brain edema and DNA injury suggesting that serine protease inhibitor may be potential therapeutic agent for ICH.
Nakamura
Takehiro
T
Department of Neurobiology and Neurological Surgery, Kagawa University Faculty of Medicine, Kita, Kagawa, Japan. tanakamu@kms.ac.jp
Kuroda
Yasuhiro
Y
Hosomi
Naohisa
N
Okabe
Naohiko
N
Kawai
Nobuyuki
N
Tamiya
Takashi
T
Xi
Guohua
G
Keep
Richard F
RF
Itano
Toshifumi
T
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects*; D001550:Benzamidines; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology; D001930:Brain Injuries / Q000188:drug therapy / Q000209:etiology; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000150:complications; D017364:Collagenases / Q000009:adverse effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D007839:Functional Laterality; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013917:Thrombin / Q000009:adverse effects
D001550:Benzamidines; D006146:Guanidines; D015842:Serine Proteinase Inhibitors; D000080242:8-Hydroxy-2'-Deoxyguanosine; D013917:Thrombin; D017364:Collagenases; C417249:collagenase 1; D003849:Deoxyguanosine; C032855:nafamostat