Effects Of Deferoxamine On Glucose Metabolism On A Rat Model Of Intracerebral Hemorrhage

Background and Purpose:Intracerebral hemorrhage(ICH) is a subtype of stroke with high morbidity and mortality accounting for about 10-30%of all strokes.Although the hematoma in humans gradually resolves,the neurological deficits in ICH patients are usually permanent and disabling.At present,there is no specific treatment for spontaneous intracerebral hemorrhage beyond supportive medical care.Several studies suggest that iron overload occurs in the brain following ICH and,an iron chelator,deferoxamine, can reduce ICH-induced brain damage,neuron death,brain atrophy,as well as neurological deficits,which suggests that iron plays an important part in brain injury after ICH.However,there is little known about the relationship between local glucose metabolism in brain and iron overload after ICH and the role of deferoxamine(DFX). The level of glucose metabolism correlates with the degree of neuronal activity.So far, the best method to make glucose quantitation in vivo is autoradiography using the tracer of 2-[18F]-fluoro-2-deoxy-D-glucose(FDG),which is the well-known radiotracer that has been frequently used as a marker of metabolic activity for glucose.Small animal Positron emission tomography(MicroPET) is a noninvasive imaging technique that allows quantitative in vivo determination of the rates of various physiologic and biochemical process with minimal invasiveness.In our study,we have co-registered a single MRI template with PET images,which greatly improves the interpretation of the PET images. Methods:A ICH model was set up by infusion of 100μl autologous blood into right basal ganglia of Sprague-Dawley rat(Wt:300 to 350 g).Rats were randomly assigned to three groups: ICH+Vehicle,ICH+DFX and sham group(n=6).In ICH+DFX group,rats received deferoxamine treatment(100mg/kg,i.p.,2 hour after ICH and at 12-hour intervals thereafter).The other two groups received the same amount of vehicle.All animals underwent 7 times MRI and MicroPET scan at pretest of ICH and 1,3,7,14,28 days after ICH,then the PET and MRI images were co-registered using ASIPro VM software to measure the glucose metabolism.Besides,we also observed the turnover of hematoma in Gradient Recalled Echo T₂^*WI sequential as well as the behavioral testings at the time point.Then we examined the effect of deferoxamine therapy on glucose metabolism after ICH and,detected amyloid precusor protein(APP) and glucose transporter-1(GLUT-1) immunoreactivity 28d after ICH.Results:Our results demonstrated that glucose metabolism in the hematoma area underwent a severe decrease 1 day after ICH and,the discrepancy between the basal ganglia in ipsilateral side and contralateral side continued to 28 days.Hematoma areas appeared as homogeneous patchy hypointension or in homogeneous hypointensity with punctuate hyperintensity on GRE-T₂^*WI.The accumulation of hemosiderin displayed clearly according to the brain sample.Treatment with deferoxamine not only significantly ameliorated the decrease in cerebral metabolic rate of glucose in the perihematoma,but also minimized the hemosiderin deposition and,improved ICH-induced neurological deficits.Effects of DFX treatment on metabolic activity of glucose is persist a long period.We also found the expression of APP increased and a declined tendency of GLUT-1 in the boundary zone of the hematoma.Conclusion:1.Glucose metabolism in the hematoma area underwent a severe decrease after ICH.2.Treatment with deferoxamine not only significantly ameliorated the decrease in cerebral metabolic rate of glucose in the perihematoma,but also minimized the hemosiderin deposition and,improved ICH-induced neurological deficits,which prompted that iron overload might participate in the processes.3.APP-positive cells could be found at 28d after ICH,which indicated the presence of axons injuries and might result in the decrease of metabolic activity of glucose in the right basal ganglia of rat after ICH.