The Effect Evaluation Of Treatment With Deferiprone Or Clioquinol In Intracerebral Hemorrhage Rats

Objective:Determine the effect of deferiprone and clioquinol on brain edema volumes and iron contents in intracerebral hemorrhage rats by MRI,compared with Perls iron staining results,brain water contents through wet or dry weight weighing methods to evaluate the consistency;Explore the relationnships between iron contents,neurological deficits and the number of FJC staining positive neurons,and evaluate the therapeutic effects of the two iron chelators.Methods:Ninety-sixth Wistar rats were randomly assigned to sham group,intracerebral hemorrhage group,clioquinol intervention group,deferiprone intervention group.Each group was divided into four subgroups depend on four observed time points: 1d, 3d, 7d,14 d.The right striatum of rats were injected with collagenase IV 0.4U,heparin 4U to build intracerebral hemorrhage models.All gavages were administered intragastrically at 6h after ICH.Deferiprone intervention group was given deferiprone gavage(125mg/kg/times,once every 12 h),clioquinol intervention group were given clioquinol(50mg/kg/times,once every 12 h),sham group and intracerebral hemorrhage control group received the same amount of solvent.Six rats of each group were used to evaluate neurological function scores and magnetic resonance imaging at postoperative each observed point.ESWAN was used for estimating intralesional iron contents,T2*WI for hematoma volumes,T2 WI for edema volumes around the hematoma at 1d, 3d, 7d, 14 d after ich.At14 days rats were sacrificed and the brains collected were used for iron staining.The remaining 18 rats per group was sacrificed for brain specimen collection of 1d, 3d, 7d three subgroups.Cut coronally at the needle eye,the front part of the brain tissue was used for brain water contents determination,the latter half was used for FJC staining and Perls iron staining.Results:Neurological deficits appeared at 6h after cerebral hemorrhage and were most severe at the first 1-3d.There was no siganificant diferences between ICH group and the sham group at 14 d.Similarly,MRI revealed that brain edema volumes around the hematoma peaked at 1-3d.No significant differences exited compared with the sham group at 7-14 d.T2*WI also showed that cerebral iron contents increased most obviously at 7-14 d,and then gradually subsided.Clioquinol significantly improved nerurological function at 3-7d,reduced brain edema volume at day 3 and cerebral iron contents around the hematoma at 3-7d and reduced the neuronal degeneration around the hematoma after surgery.However,deferiprone significantly reduced iron contents at 3-7d,without decreasing edema volumes,neuronal degeneration around hematoma,and alleviating nerurological deficits.Correlation analysis showed ESWAN sequence amplitude log value negatively correlated with Perls iron staining results(r=-0.872),and brain edema volumes positively correlated with water contents by means of weighing wet and dry weight(r=0.875). Brain edema volumes and water contents positively correlated(r =0.875).Edema volumes(r=-0.965),the number of FJC staining positive neurons(r=-0.84),behavioral scores(r=-0.898) all negatively correlated with ESWAN sequence amplitude log value.The number of FJC staining positive neurons(r=0.881) and behavioral scores(r=0.898) both positively correlated with edema volumes.Conclusion:Clioquinol can significantly reduce the iron contents, the number of FJC positive neurons,brain water contents around the hematoma,significantly improved functional deficits,presumably associating with clioquinol neuroprotection.Deferiprone showed no neuroprotection.