Efficacy of recombinant annexin 2 for fibrinolytic therapy in a rat embolic stroke model: a magnetic resonance imaging study.
Efficacy of recombinant annexin 2 (rAN II) in a rat model of embolic stroke was examined using a magnetic resonance imaging (MRI) and histology. The right middle cerebral artery of male Wistar rats was occluded by autologous clots under anesthesia. Four doses of rAN II (0.125, 0.25, 0.5 and 1.0 mg/kg, n=10 for each group) or saline (1 ml/kg, n=10) were administrated intravenously within 5 min before clot infusion. Serial changes in apparent diffusion coefficient (ADC) and relative blood flow (CBF) were measured with the use of MRI in half of the animals in each group. The remaining half of the animals in each group was evaluated for hemorrhage and final infarct size by histology at 48 h after embolization. At 3 h after embolization, lesion volumes with ADC were abnormality and CBF in the peripheral lesion was improved in groups treated with 0.25, 0.5 and 1.0 mg/kg, but not 0.125 mg/kg, of rAN II in comparison with the saline-treated group (P<0.05). Histological analyses were consistent with MRI findings. More importantly, no hemorrhagic transformation was documented in rats treated with 0.125 and 0.25 mg/kg of rAN II, whereas it was observed at higher doses. We concluded that rAN II at 0.25 mg/kg significantly reduced infarct size and improved CBF without hemorrhagic complications. rAN II is a novel compound that has the potential to be a promising fibrinolytic agent to treat embolic stroke.
Tanaka
Yoji
Y
Department of Neurosurgery, Tokyo Medical and Dental University, Tokyo, Japan.
Ishii
Hideto
H
Hiraoka
Megumi
M
Miyasaka
Naoyuki
N
Kuroiwa
Toshihiko
T
Hajjar
Katherine A
KA
Nagaoka
Tsukasa
T
Duong
Timothy Q
TQ
Ohno
Kikuo
K
Yoshida
Masayuki
M
D000704:Analysis of Variance; D000818:Animals; D017306:Annexin A2 / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004617:Embolism / Q000150:complications; D008279:Magnetic Resonance Imaging; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000627:therapeutic use*; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D015912:Thrombolytic Therapy / Q000379:methods*; D013997:Time Factors
D017306:Annexin A2; D011994:Recombinant Proteins