Study Of The Neuroprotective Effect Of Tacrine On Cerebral Ischemia-reperfusion Injury

Stroke is one of the three most serious diseases among human beings, which havefour high rates of morbidity, disability, mortality and recurrence. Vessel occlusion(ischemic stroke) is the most common stroke. Currently, one of the clinical treatmentsfor the ischemic stroke is the use of thrombolysis drugs in combination with theneuroprotective drugs. Thrombolysis drugs have achieved a relative good development,while there are still a lot of difficulties in the research and development ofneuroprotective drugs. The main problem is how to protect reperfusion injury afterthrombolysis treatment. Therefore, it is very important to develop neuroprotectivedrugs for cerebral reperfusion injury.Objective：To investigate the neural protective effect of Tacrine on the cerebralischemic reperfusion injury in rats.Method: Focal cerebral ischemia-reperfusion models were established with threadembolism method. The chemicals or artificial cerebral spinal fluid (CSF) were injectedinto the lateral ventricle3min before ischemia. The perfusion was restored after40min ischemia. In the dose-dependent experiments, the rats were divided into fivegroups, one ACSF group and four Tacrine treated groups in a10-fold increase in theconcentration (0.04-40μg/kg). The Longa’ score was used to evaluate the animalmovement behavior and TTC staining to evaluate the infraction volume24h afterischemia/reperfusion. In addition, we observed the long-term effects of Tacrine on theischemia/perfusion injury. The rats were randomly divided into three groups (Tacrinetreated group, tetraethylammonium (TEA) treated group and ACSF group). TheLonga’s scores were also recorded24h after ischemia/reperfusion for the survivedanimals, which were housed for a maximum of two weeks. The mortality of animalswas recorded every day from24h to two weeks after ischemia/reperfusion. Finally, weevaluated the infraction volume with TTC staining as mentioned above for the animalssurvived for two weeks.Results: We found a dose-dependent effect of Tacrine on the infraction volume and therats treated with Tacrine had lower infraction volume than that in control group. Thebest effect was achieved in a dose of40μg/kg Tacrine. Furthermore, a single injection of Tacrine(40μg/kg) into the lateral ventricle had a long-time (two weeks)neuroprotective effect, as it was demonstrated that the mortality was no differencebetween the Tacrine treated group and TEA treated group (P>0.05), but wassignificantly lower than that in control group (P<0.05). In addition, the Longa’s scoreand infraction volume of the Tacrine treated group or TEA treated group were alsolower than that in ACSF group (P<0.05).Conclusion： These results suggest that Tacrine may have neuroprotective andtherapeutic effects on focal cerebral ischemia and perfusion damage in rats.