| Background: The study on neuroprotection of penumbra in ischemic cerebral vascular disease is invariably focal and difficult point of basical and clinical research in cerebral vascular disease. Although it have been made great progress in related field of basical study such as hypothermia therapy, calcium channel blocking agent, anti- excitatory amino acids and cleaning free radical, these methods are not still applied extensively in clinic. Recently with the clarification of mood disorder neurobiological alteration and mechanism of antidepressants, study emphasized from releasing and metabolism change of neurotransmitter to regulation of some protecting gene such as bcl-2, TrkB, BDNF ect and neuroprotecting cytokine. Fluoxetine hydrochloride is a SSRI taken orally which inhibits the function of absorbing pump in presynaptic membrane, increases 5-HT level in synaptic cleft. 5-HT sufficiently binding to the receptors on postsynaptic membrane can achieve pharmacological action. This drug is a classical SSRI which have been clinically used for long time in our country. It was used extensively and the prise is low. Some studies overseas confirmed that fluoxetine have neuroprotection effect, but the mechanism which is after the receptor and in the cell is unclarified. Neuroprotection of antidepressants was reported rarely. Discussing fluoxetine' s mechanism after the receptor and its effect on ischemic cerebral vascular disease can help to find the mechanism of SSRI. It will be in favor of discovering a new thinking and method of42001neuroprotection in cerebral vascular disease.Objectives:By observing the changing of TrkB and bcl-2 in ischemical reperfusion injury models ' penumbra and hippocampus after fluoxetine pretreatment and the changing of TrkB and bcl-2 in normal rats after fluoxetine pretreatment , we discussed as follows:!. Fluoxetine pretreatment' effect on the expression of TrkB and bcl-2 in normal rats. 2. Fluoxetine pretreatment ' effect on the expression of TrkB and bcl-2 in ischemical reperfusion injury models . 3. The mechanism of fluoxetine's neuroprotecting action after the receptors. 4. To look for a new way of neuroprotection which is better in clinic.Methods: In this experiment, we filling fluoxetine into the stomach for 20 days. Part of rats were made into models of focal cerebral ischemical reperfusion injury with thread. We appled SABC immunohistochemistry to detect the expression of Bcl-2, and Elivension immunohistochemistry to detect expression of TrkB. Then we used image analysis system , one way ANOVA and t test to analyse their changes and to discuss post receptor mechanism of fluoxetine.Results: Immunohistochemistry rsult: (1) TrkB Expressed more in sigle administrated group than in normal control group (p<0.05), and TrkB Express more in fluoxetine pretreatment operation group than control operation group (p<0.05) . (2) Bcl-2 is not expressed in hippocampus both in normal control group and in single administrated group. Bcl-2 expression have no differences in both fluoxetine pretreatment operation group and control operation group (p>0. 05) .52001Conclusions:Our study suggests:(1) Fluoxetine have neuroprotection effect on penumbra (2) Fluoxetine may have neuroprotection effect through increasing the expression of TrkB way (PKA-CREB-BDNF-TrkB). (3) That Fluoxetine has no direct effect on the expression of antiapoptosis gene bcl-2 but has great effect some paths including TrkB way suggests that its neuroprotection effect can be achieved by these ways.
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