Anti-inflammation Mechanism Of Vinpocetine In Acute Ischemic Stroke Patients

Peripheral lymphocytes entering brain ischemic regions orchestrate inflammatory responses, release of inflammatory factor, catalyze cerebral dedma and tissue death, finally worsen clinical outcomes of acute ischemic stroke(AIS). So immunodepression and the application of immunomodulatory drugs after AIS become a foucas of attention recently. But all of them inhibiting central immune response while inhibiting periperal immune reaction at the same time. This led to increased incidence of infection after stroke. Therefore, developing a unique antiinflammatory agent of AIS without significant adverse effects is urgently needed. In this open-label, evaluator-blinded, parallel-group clinical pilot trial, we recruited 40 patients matched for clinical and MRI characteristics, with anterior cerebral circulation occlusion and onset of stroke that had exceeded 4.5 hours, who then received standard management alone(controls) or standard management plus vinpocetine(Vinp, Gedeon Richter Plc.), 30 mg per day introvenous for 14 consecutive days. Vinpocetine, a derivative of the alkaloid vincamine, has long been used for cerebrovascular disorders and cognitive impairment. Vinpocetine inhibits NF-κB–dependent inflammatory responses by directly targeting IKK have been recognized in animal experiments. Its role in inhibiting inflammation among AIS patients, however, remains unexplored. Here, we show that vinpocetine acts as an anti-inflammatory agent in AIS patients. Vinpocetine does not change the number of lymphocytes but inhibits NF-κB activation not only by directly targeting IKK inhibited phosphorylation and degradation of IκBα, but also increasing the expression of IκBα m RNA and then inhibiting subsequent induction of proinflammatory mediators, including TNF-α, IL-6, MCP-1, VCAM-1 and ICAM-1. We also compared the changes of infarct volume, cytotoxic edema and inflammation degree between control and vinpocetine groups by means of nuclear magnetic resonance imaging(NMRI). Compared with the 20 control patients, the 20 vinpocetine recipients had smaller infarct volume, sligtly cytotoxic edema and inflammation reaction at day 7. These studies thus identify vinpocetine as a unique antiinflammatory agent that may be repositioned for the treatment of AIS.