The Effects Of Catalpol And Its Action Mechanism In Gerbils Ischemia-Reperfusion Model

The purpose of this study mainly aims at observation the effects of catalpol and its action mechanism in gerbil global cerebral ischemia-reperfusion model.Global cerebral ischemia is induced by transient bilateral occlusion of the common carotid arteries with non-traumatic micro aneurysm clips. Histological and morphologic as well as behavioral analysis is used to evaluate the model and the effects of catalpol. 5-min ischemia induces the disappearance of microtubule associated protein-2 in hippocampal CA1 neurons and the death of large number neurons as well as the formation of broad brain infarct and the damage of cognitive ability of gerbils.Catalpol used in short term (consecutively intra-peritoneal injection 4 days) mitigates the damage induced by ischemia-reperfusion and presents neuroprotection in the situation in which catalpol is given within 3h after reperfusion. Catalpol at the dose of 1mg/kg can significantly rescue neurons in hippocampal CA1 subfield and reduce cognitive impairment. The neuroprotective efficacy of catalpol becomes more evident at the doses of 5mg/kg and 10mg/kg. Of great importance is the finding that the neuroprotective efficacy of catalpol still can be seen even when the observational period is lasted out 35 days after ischemia. Although catalpol can also protect against neuronal death when the treatment is delayed up to 6 h after reperfusion, it can not ameliorate the animal cognitive ability. So we conclude that therapeutic time-window for catalpol in gerbil global cerebral ischemia model should be limited within 3 h after ischemia.Catalpol given in long term (consecutively intra-peritoneal injection 10-14 days) can not only obviously ameliorate the learning and memory ability in gerbils whose cognitive ability are innate weak, but also markedly improve the cognition of gerbils subjected to brain ischemia even in the situation in which catalpol is used up to 6h after reperfusion. All these suggest that catalpol may be of different pharmacological activity in different condition, namely, trophic function may be primary in long term using, on the contrary, neuroprotection is predominant.The neuroprotective mechanism of catalpol is further studied in vivo using electron...