Background and Objective: Working memory impairment and anxiety behavior could be induced by transient global cerebral ischemia/reperfusion (TGCI) as one model of brain stroke. Menaquinone 4 (MK-4) is an antioxidant and anti-inflammation known as vitamin K2. This investigation questioned the effects of MK-4 on the mentioned cognitive impairments following TGCI. Materials and Methods: 28 male wistar rats were randomly selected and divided in 4 groups: sham-control, TGCI, TGCI+DMSO (1% v/v), TGCI+ MK-4. Immediately and also 2 hours after reperfusion, 200mg/kg MK-4 were injected intraperitonially. 7 days later rats were examined using Y maze and also open field apparatus to evaluate working memory sufficiency and the level of anxiety behavior, respectively. Results: TGCI could reduce spontaneous alternation compared with the sham-control group significantly (p < 0.01). But MK-4 increase percentage of spontaneous alternation compare to TGCI and TGCI+ DMSO (p < 0.05). Rats in TGCI + DMSO and TGCI groups spent significantly less time in the center zone of open field apparatus compared to sham-control group which can be interpreted as the elevation of anxiety behavior (p < 0.001). But the time spent in the center zone was significantly increased in TGCI+MK-4 group compare with injured groups (p < 0.001). Conclusion: Results showed that MK-4 could improve working memory (short-term memory) and also reduced anxiety behavior after TGCI. Probably, antioxidant and anti-inflammatory aspects of MK-4 decrease oxidative stress and neuro-inflammation proceeding factors in the brain which needs more investigations.

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