The Neuroprotective Effects Of Deferoxamine In Neonatal Rats With The Hypoxic-ischemic Brain Damage

Objective:To explore the neuroprotective effects of early intervention of deferoxamine (DFO) on neonatal rats with hypoxic-ischemic brain damage (HIBD) by testing expression of bromodeoxyuridine (BrdU) and nestin in the dentate gyrus region which means the activation of endogenous neural stem cells (NSCs); and also the improvement of learning and memory capabilities as an evidence of the neuroprotective effects of DFO were examed in neonatal rats with HIBD. Methods:The HIBD model was made in 7 days old Wistar rats and the rats were divided into 3 groups randomly:sham operation group, control group of HIBD, DFO treated group. Histological examination of the CA1 hippocampal region of the damaged hemisphere was conducted by haematoxylin-eosin (HE) stain with optical microscope and the body weight of the rats were measured. Expressions of nestin and BrdU in the CA1 hippocampal region were tested by indirect immunofluorescence labelling of paraffin-embedded tissues and image quantitative analysis through computer at 4th days after operation and learning and memory capabilities of each group were evaluated by Morris water maze at the age of 32 days after birth. Results:1. There was significant difference in increase of body weight among the three groups (P<0.05). The sham operation group had a significantly higher increase in body weight than the other two groups.2. Anatomical pathology revealed the pale area in some right hemisphere of the rats at 4th day after hypoxia and cerebral atrophy and cavitas at the age of 32 days after birth.3. Histopathological changes (HE staining):There were no morphological anomalies in the sham operation group. The neuron number in the CA1 pyramidal cell layer of the right hippocampus was decreased and the cells arranged in disorder in the control group of HIBD. At the same time, lots of neurons were necrotic and had karyopycnosis in the CA1 region. Compared with the control group of HIBD, the necrotic neurons in the CA1 region were obviously reduced in the DFO treated group.4. Expression of nestin:There was significant difference in the expression of nestin in the DG hippocampal region among the three groups (P<0.05). Measurement of the fluorescence intensity of nestin-positive cells revealed that the DFO treated group was the highest compared with the control group of HIBD, while the sham operation group was the least (P<0.05).5. Expression of BrdU:There was significant difference in the expression of BrdU in the DG hippocampal region among the three groups (P<0.05). Measurement of the number of BrdU-positive cells revealed that the DFO treated group was the maximum compared with the control group of HIBD, while the sham operation group was the minimum (P<0.05).6. The use of Morris water maze in learning and memory:Both the latencies to find a hidden platform in the water maze on 5 consecutive days and the annulus-crossing index had significant differences among the three groups (P<0.05). The annulus-crossing index in the control group of HIBD was the minimum. But there was no significant difference between the sham operation group and the DFO treated group (P> 0.05). Conclusions:1. Expression of the endogenous NSCs increased in neonatal rats with HIBD, it means that the endogenous NSCs were activated after HIBD.2. Early intervention of DFO to the neonatal rats with HIBD can reduce the damage of the neurons in pathology.3. Early intervention of DFO to the neonatal rats with HIBD can increase the expression of BrdU and nestin, which means early intervention of DFO can improve the regeneration of the endogenous NSCs.4. Early intervention of DFO to the neonatal rats with HIBD can improve the capabilities of learning and memory which were waken due to HIBD.