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Focal Cerebral Ischemia Model by Endovascular Suture Occlusion of the Middle Cerebral Artery in the Rat
Published on: February 5, 2011
Nattokinase Attenuates Acute Cerebral Infarction in a Rat Model of Middle Cerebral Artery Occlusion
Takashi Tanikawa1, James Yu2, Kate Hsu2
1School of Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Saitama, Japan; tanikawa@josai.ac.jp.
Background/Aim:
Nattokinase (NK) is a potent serine protease with various pharmacological properties that include thrombolytic, anti-inflammatory, and antioxidant activities. The aim of this study was to investigate the neuroprotective effects of NK in transient middle cerebral artery occlusion (MCAO)-induced cerebral ischemia-reperfusion injury and determine the mechanisms underlying the effects of NK.
Materials And Methods:
Rats were administered NK (65 and 130 mg/kg body weight, p.o.) daily for seven days prior to MCAO surgery. The infarct volume, behavioral tests, clotting time, and antioxidant markers in the MCAO model rats were assessed. The involvement of various cellular pathways in the effects of NK was examined.
Results:
NK treatment dose-dependently reduced infarct volume and prolonged clotting time in MCAO model rats. Transcription factor activity analysis revealed the involvement of nuclear factor erythroid 2-related factor 2 (Nrf2) activity and enhanced antioxidant enzyme expression following MCAO.
Conclusion:
Oral nattokinase confers early neuroprotection after experimental cerebral ischemia through Nrf2-associated antioxidative modulation and a mild, transient anticoagulant effect, supporting its potential as an orally available adjunct in ischemic stroke management.

