The Protective Effect Of Deferoxamine In The Hypoxic-ischemic White Matter Injury

This paper aims to investigate the protective effect of DFO in treating the hypoxic-ischemic White Matter Injury(WMI), by observing the Deferoxamine neuroethology, brain tissue morphology of rat and the influence of myelin basic protein expression. A three-day neonatal mouse model of hypoxic-ischemic WMI was used to examine the effect through the separate ligation of bilateral common carotid artery combined hypoxia. [Method]1.To study the protective effect of Deferoxamine, the author divided the neonatal SD mice into three groups: the deferoxamine(DFO), the normal saline(NS), and the blank control group. The models of deferoxamine and the normal saline groups are built through the separate ligation of bilateral common carotid artery combined hypoxia. The DFO was injected into the deferoxamine mice by peritoneal puncture according to 100mg/kg. The normal saline was injected into the saline mice in the same way. And the model of the blank control group was built by separating the bilateral common carotid arteries, but without ligation and without hypoxia.2. Observation the body quality changes of rats 3 days age to 21 days age. We use Morris water maze to test changes of neural behavior in different groups of rats on the 21 st day after administration. During building the models, the author, by studying neuroethological behaviors of the mice, can evaluate the idealness of the model. By using HE dye, we can observe brain tissue pathomorphology on the 28 th day after ministration. At the same time, we can observe myelin damage respectively by MBP immunity. Real-time PCR compares MBPm RNA expression of ventricle narrator mass between different tissue sample. [Result]1. The neonatal mice got ligation of bilateral common carotid artery combined hypoxia, which led to hypoxic-ischemic brain damage. Observation the body quality changes of rats 3 days age to 21 days age: The body of quality at the age of 3 days the blank controlled group?the normal saline group?the deferoxamine group is 8.97 ±0.81g?8.62±0.68g?8.96±0.74 g. There was no statistically significant difference of weight(P?0.05). The body of quality at the age of 5 days, the three groups became 11.32±0.43g?9.31±0.82g? 9.70±0.57 g. The data is on rise. Difference between groups was statistically significant(P?0.01).2.In Morris water maze, the average incubation period of the deferoxamine group ?the normal saline group?the blank controlled group are 11.33±3.97s?14.82±1.75s?6.88±3.61 s. The average swimming speed to find the platform in the water on the sixth day are 74.17±13.16cm/s?59.75±19.82cm/s?89.55±11.70cm/s. Through the number of the targer area on the sixth day are3.75±1.29?2.62±1.63?5.35±2.04. Target quadrant residence time percentage are 31.5±5.90%?20.63±3.33%?51.32±8.12%. Difference between groups was statistically significant(P?0.01). The deferoxamine group learning and memory ability was improved than NS group.3.Brain tissue HE dye: the paraffin section shows that blank cotroll group(the cortex, hippocampal gyrus, subcortical white matter, brain periventricular white matter), their brain cell density?organizing clearance closely and fiber arranged orderly. The saline group brain tissue are loose and dropsy, and their fiber arranged random. Comparing with the normal saline group, the group mice injected with Deferoxamine, their brain tissue are more dense; edema gets relieve; fiber range are more ordered.4. Brain tissue MBP immunohistochemistry: the model group observation of the cortex, hippocampal gyrus, subcortical white matter. In the same place, MBP staining intensity between the blank control group, the normal saline group and deferoxamine group have statistical significance(P<0.001). The blank control group had the most obvious dying, But the normal saline group had the weakest dying. The tissue staining of the deferoxamine group weaker than that of the blank control group(P<0.0125)and higher than that of the normal saline group(p<0.0125).5.Realtime fluorescence quantitative PCR(RTFQ PCR): We observed the expression level changes of MBPm RNA between different groups chamber of the narrator. The results show that the blank control group has more MBP m RNA expression than the NS group. And the DFO group are between the two groups. [Conclusion]1.The method of building WMI SD mice model, which combines ligation of bilateral common carotid artery and hypoxia, could be used to study premature infant hypoxic –ischemic brain damage.2.Hypoxic-ischemic brain disease occurrence mechanism is closely related to brain iron metabolism.3. DFO can cross the blood brain barrier and combine with nonprotein iron chelation. It make the iron distribution in the extracellular space without enterring cells. It reduced the hydroxyl free radical formation, reduced lipid peroxidation. It has protective effect on hypoxia ischemic cerebral white matter lesions.