| Objective:The pathogenesis of migraine still remains unclear.Previous studies have suggested that the activation of the trigeminovascular system plays an important role in the development of migraine.This study aims to explore the changes of regional cerebral blood flow in mice induced by intracortical KCl stimulation,and eliminate the effects of direct stimulation of the dura mater,and whether the trigeminal nucleus caudalis(TNC)can be activated by the effetrent modulatory pathways and the occurrence of pain-related behavior in freely moving mice.Rizatriptan is the first-line recommended drug for acute migraine attacks.The rizatriptan intervention is used to further clarify the relationship between this model and migraine,and to explore its feasibility as a migraine model.Methods:Mice were randomized into three groups:control group,KCl group and rizatriptan intervention group.The control group was injected with 1 ?l of saline in the cortex;the KCl group was injected with 1 ?l 1M KCl in the cortex,and the rizatriptan group was given of rizatriptan 30 minutes before intracortical injection of 1?l 1M KCl.First,under anesthesia,the changes of cerebral blood flow(rCBF)were observed by laser speckle blood flow imager.The behavioral changes of mice were observed under awake conditions.The expression of c-Fos in the TNC was studied by immunofluorescence staining.Results:Administration of 1 ?l 1M KCl in the cortex caused significant changes of rCBF and increased the time of scratching and freezing,and decreased the total distance of activity in freely moving mice.While the intervention with rizatriptan did not affect the rCBF caused by KCI stimulation in the cortex,it significantly reduced the time of scratching and reduced the expression of c-Fos in TNC caused by stimulation with KCl in the cortical.Conclusion:These data suggest that intracortical administration of KCl stimulation can result in the generation of CSD,and CSD may activate the trigeminovascular system through the efferent modulatory pathways leads to the occurrence of pain-related behavior in mice.Objective:To establishing a stable model of cortical spreading depression in mice,and study the effect of topiramate on regional cerebral blood flow caused by cortical spreading depression.Methods:The model of CSD in mice was constructed by intracortical injection with KCl in the occipital cortex.Fifteen mice were randomly divided into CSD group(n=5),topiramate intervention group(n=5),and control group(n=5).For mice in the CSD group,CSD was induced by intracortical injection of 1 ?l KCl solution(1 mol/L);for mice in the topiramate intervention group,topiramate(30 mg/kg)was intraperitoneal injection 30 minutes before 1 ?l KCl(1 mol/L)stimulation in the occipital cortex;for the control group,1 ?l of saline was injected into the occipital cortex.Three groups of mice were placed under a laser speckle blood flow imager to observe the production of CSD and the changes of rCBF before and after the stimulation.Results:The model of cortical spreading depression in mice was successfully constructed by intracortical injection of KCl solution in the occipital cortex.At region of interest 1(ROI1),the changes of rCBF in CSD group was 68.05%± 21.0%,and the changes of rCBF in the topiramate intervention group was 27.20%± 18.25%.Compared with the CSD group,the blood flow amplitude of the topiramate intervention group was Siguificantly reduced(P=0.011).At region of interest 2(ROI2),the changes of rCBF in the CSD group was 70.18%± 13.07%,and the changes of rCBF in the topiramate intervention group was 27.71%±13.52%,compared with the CSD group,the changes of rCBF in the intervention group was significantly reduced(P=0.001).There was no CSD in the control group,and there was no significant change of rCBF before and after stimulation.Conclusion:Topiramate can significantly reduce regional cerebral blood flow changes caused by cortical spreading depression. |
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