Experimental Study On Ferrous Iron Overloading And Related Transporters In Brain Tissue After Intracerebral Hemorrhage In Rats

Objective:Intracerebral hemorrhage (ICH) is one of the critical type in the cerebrovascular disease. It causes vital threat to human health owing to the high incidence, high morbidity and high mortality. The delayed brain damage after ICH is an important factor to influence the prognosis of such patients, but the mechanism is complicated and not well understood. Iron accumulation after hemolysis possibly contributes to brain delayed insults and severe neurological deficits post-hemorrhage in the hematoma after ICH, And the expression of iron metabolism related proteins is also abnormal. In rat ICH models with type IV collagenase, by surveying ferrous iron sediments and divalent metal transporter1(DMT1), ferroportin1(FP1) in different time after ICH and their spatio-temporal relations, our study is to explore the role of Fe2+, DMT1and FP1in the mechanism of delayed brain insults result from iron.Methos:52healthy adult SD rats with weight of250-300g were used; they were randomly divided into3groups:ICH models, sham operation controls and health controls. ICH was established by infusing2.5μl saline(containing0.5U type Ⅳ collagenase) into rat globus pallidus; normal saline was injected in sham operation controls. Observe the ferrous iron aggradation. DMT1and FP1protein expressin of brain slices with iron staining and immunohistochemistry staining methods, they were tested respectively in each group at lday,3day,7day and14day.Results:1. Macroscopically the hemisphere with hematoma swell obviously especially at3day and7day:2. The ferrous iron sediment were more increased at3day.7day and14day in ICH models than controls and reached top at14day;3. DMT1immunopositive cells mostly located in neuron, gliocyte and endotherlial cell. As compared with the sham operations, there appeared a significant increase of DMT1immunopositive cells at each time in ICH models, and reached the plateau at7day:4. Most FP1immunopositive cells were the membrane of neurons and glias. The numbers of FP1immunopositive cells at each period and reached its summit at7-14day;5. Correlation test showed that there were positive relations between the ferrous iron sediment and DMT1immunopostive cells, FP1immunopostive cells; FP1expression was significantly parallelled with DMT1.Conclusions:1. The hematoma of rat ICH model established by type IV collagenase is reliable;2. Ferrous iron overload resulting from ICH possibly are important causes of the delayed brain insults;3. Ferrous iron overload after ICH possibly intensify DMT1and FPl expression;4. DMT1and FP1maybe transport ferrous iron from brain after ICH.