| Background and ObjectivesHydrocephalus is one of the commonest complications of intracerebral hemorrhage (ICH). Intraventricular hemorrhage (IVH) would take place in more than 50% cases of intracerebral hemorrhage and progressive post-hemorrhagic hydrocephalus (PHH) would occur in about 35% patients with IVH . PHH always induce secondary injury of brain, and is a significant and independent contributor to mortality in intracerebral hemorrhage patients. Up to date, the definite pathogenesis of posthemorrhagic chronic hydrocephalus remains unclear and it is difficult to be prevented and cured at earlier time. Studies showed that iron , the hematological catabolin, play a key role in secondary brain injury after ICH. After IVH, the concentration of iron elevatered obviously, therefore, it is worth to investigate the relations between iron and PHH. So we established a chronic hydrocephalus model after IVH in rats, the ratio of hydrocephalus in different concentrations of iron were observed as well as the roles and possible mechanisms of the iron, ferritin and deferoxamine in the onset of PHH were discussed.Methods:1. 269 Sprague Dawley female rats were divided into 7 groups randomly: the saline control group (n=58), the IVH group (n=63), the deferoxamine group (n=63), the artificial CSF control group (n=30), The iron group (n=30),the semis-iron group (n=15), and the normal group (n=10);2. The rat hydrocephalus model were made by twice infusing autologous whole j veinous blood (130μl) into the right lateral cerebral ventricle to establish the IVH group and the deferoxamine group. The saline group was made by twice injecting 130 ul saline. 5μl FeC13 dissolved in artificial CSF with the concentration of 6.67 g/L or 3.33 g/L were slowly infused into the right lateral cerebral ventricle of the rats in the iron group and in the semis-iron group. The rats in the artificial CSF control group were infused 5μl artificial CSF. Rats in the normal control group were fed without any treatment to 28 day.3. The rats were sacrificed in 1, 3, 7, 14, 28 days for measurement of the transverse diameter of the lateral ventricle on the coronal slices of brain 0.40 mm posterior to the bregma for evaluation of hydrocephalus and the index of ventricle, as well as pathology were observed.4. The behavioral changes were observed by Morris water maze at 14 and 28 days in the saline contral group, the IVH group, the deferoxamine group and the normal control group.5. Expressions of ferritin in the cerebral cortex, callosum and corpora striata were observed with immunohistochemistry (IHC) in the normal control group, the saline group, the IVH group and the deferoxamine group.Results:1. At 28 days, hydrocephalus were not occurred in rat of the normal control group, the saline control and the artificial CSF control group. There were significant differences of hydrocephalus between the IVH group (73%) and the deferoxamine group (27%) (P < 0. 05). Similarly, hydrocephalus in the iron group (9/10) was not the same as that in the semis-iron group (1/5) obviously (P < 0. 01).2. The indexes of ventricle in IVH group (4.53±1.70) were higher than the deferoxamine group (2.77±1.53) and the saline control group (P < 0. 05). The indexes of ventricle in iron group (6.87±2.19) were higher than the semis-iron group (3.32±0.95) and the articial CSF control group (1.09±0.45) (P < 0. 01).3. Behavioral changes were no difference in the saline group, the IVH group and the deferoxamine group at day 14. At 28 days, The escape latency time in the IVH group (16.36±5.93 s) were higher than the saline control group (8.21±2.00 s) (P < 0. 01), however, the strategy of finding platform in the IVH group (3.00±0.00) were lower than the saline control group(3.75±0.50) ( P < 0. 01). The escape latency time of the deferoxamine group (11.38±2.57 s) was shorter than that of the IVH group (16.36±5.93 s) and the strategy of finding platform (3.25±0.50) was higher than that of the IVH group (3.00±0.00), but there was no statistically distinction, as well as that between the deferoxamine group and the saline group.4. The brain morphology and structure presented by light microscope and TEM were normal in the normal control group, the saline group and the artificial CSF group. In the IVH group, edema of white matter surrounding ventricle, twist and engorge of callosum, proliferation of rhagiocrine cells as well as haemosiderin deposit were observed. But it was not found haemosiderin deposit in the deferoxamine group. In the iron group, cellular proliferation surrounding ventricle, edema of choroid plexus, deposit of haemosiderin, absence of ciliums and microvillares of the ependymal cells were observed. The pathological changes in the semis-iron group were lessened than that in the iron group. There were no significant changes by Nissl's staining in the experiment.5. Ferritin, which expressed in all kinds of brain cells in the normal control group, increased at 1 day, peaked at 7 days, and descended in the saline control group, the IVH group and deferoxamine group. The ferritin stayed at high level till 28 days in the IVH group, while that return to normal at 14 days in the saline group. And ferritin in the deferoxamine group was lower than that in the IVH group at 28 days (P<0.05).Conclusions:1. Because of the characteristics of high survival rate and easy to breed, the posthemorrhagic chronic hydrocephalus model in the experiment prepared by twice injecting unanticoagulation auto- venous -blood in the lateral cerebral ventricle is very useful, and it can imitate the clinical changes of the posthemorrhagic chronic hydrocephalus.2. Hydrocephalus, which induced by injecting iron into the lateral cerebral ventricle, is relevant with the dosage and the of iron closely, suggested that iron maybe play an important role in the course of hydrocephalus.3. The content of iron , decomposition product of blood in the cerebrospinal fluid, may concerned with hydrocephalus after IVH. However, the deferoxamine could decrease the posthemorrhage chronic hydrocephalus through reduce the deposition of hemosiderin, relieve the expanding of the ventricle.4. The increasing expression of ferritin in the rat model indicated that it may promote the development of the hydrocephalus.5. Deferoxamine can decrease the expression of ferritin in the posthemorrhagic chronic hydrocephalus rats, but the effect is limit because of the ferritin remain higher than normal at corpora striata and cerebral cortaex till 28 days. The reason may due to the posthemorrhagic oedema of the brain, the compression of hematoma and the dosage of deferoxamine.
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