The Effect Of Platelet-activating Factor On GFAP Expression And Spreading Depression During Local Cerebral Ischemia

Objective: To observe the change of glial fibrillary acidic protein(GFAP) expression in the penumbra,distant of infarct and contralateral cortex respectively in tree shrews at different time after thrombosis cerebral ischemia ,and the effect of platelet- activating factor(PAF) receptor antagonist ginkgolide B(GB) on GFAP expression in astrocytes.Simutaneously,we also investigate the relationship between PAF and cultured neuronal viability or GFAP expression in cultured astrocytes. Through experimental results we would explore the modulation of PAF in astrocyte proliferation and the mechanism in cortical spreading depression(CSD), so we can provide the new proof for prevention and treatment in clinical cerebral ischemia. Methods: The focal thrombotic cerebral ischemia is formed by photochemical reaction in tree shrews.The absorbance of GFAP expression in astrocytes were detected by immunohisto-chemistry. PAF was added into the cultured neurons and astrocytes with 4.8,16 and 20μmol/L,and was cultured for 4,24 and 72h respectively. MTT method and immunohistochemistry was used on cultured neuronal viability and GFAP expression in cultured astrocytes respectively. Results: GFAP expression in astrocytes in the penumbra,distant of infarct and contralateral cortex didn't change at 4h after local cerebral ischemia, but increased significantly at 24h inthe penumbra(P<0.01),and retained the higher level at 72h(P'<0.01).whereas GFAP expression began to increase at 72h in the distant of infarct and contralateral cortex(.P < 0.05). Giving experimental animals GB at 6h,GFAP expression declined. During different time after adding PAF with different concentration into cultured neurons and astrocytes respectively, neuronal viaibility declined in dose- and time- dependent, and with dose increasing and time prolonging, the number of astrocytes decreased, but GFAP expression in survival astrocytes increased and was the highest level at 72h(P<0.01). Conclusions: Astrocytes proliferate and GFAP expression increase in the penumbra, distant of infarct and contralateral cortex after local cerebral ischemia, of which the astrocytes proliferation in the distant of infarct and contralateral cortex could be a extraordinary phenomenon of cortical spreading depression.PAF can decline neuronal viability and increase GFAP expression in astrocytes,whereas its antagonist GB decreases GFAP expression. Results indicate that PAF-astrocytes interaction involves in the ischemia cerebral injury, and maybe exist the closer relationship with CSD.