ABSTRACT
Objective To simulate the process of hypoxic?ischemic brain injury at high altitude in a simulated cabin with plateau low pressure environment, and to prepare a rat model of cerebral injuries at different high altitudes. Method Thirty?two 0?day?old neonatal SD rats were divided into four groups, namely group A ( control group) and three test groups:group B (2000 m group), group C (4000 m group), and group D (6000 m group). The rats of control group were reared in a barrier environment. The rats of test groups were placed in a simulated cabin with plateau low pressure environment, and to prepare neonatal cerebral ischemia?hypoxia model by sport activities. The sport movements were carried out in the cabin in a swimming groove 60 min/d, and not less than 20 hours a day at high altitude low pressure environment. Zea Longa 5 point scale standard was used to determine the behavioral scores at the 3 th 7 th 11 th 15 th days, and samples were collected on the 15th day to observe red blood cell morphology using HE and 2, 3, 5?triphenyltetrazolium chloride ( TTC ) staining and ultrastructure by scanning electron microscopy. Result ( 1 ) The neurological scores of the test groups A, B, C were significantly different from that of the control group (P<0?05), and the scores of test group D and control group were very significantly different ( P <0?01 ) . ( 2 ) The histopathological examination using HE staining showed inflammatory cell infiltration in all rats of the test groups, and the extent of inflammatory cell infiltration was positively correlated with the increase of altitude. ( 3 ) The histopathology with TTC staining revealed prominent ischemia in the cerebral cortex of rats in the plateau hypoxic environment. ( 4 ) Scanning electron microscopy showed that the rat erythrocytes were cap?like in the group B, irregular in the group C, and zigzag shape in the group D. Conclusions In this study, a rat model of neonatal hypoxic?ischemic encephalopathy ( HIE) is successfully established by hypoxic cabin combined with sport activity. This model is stable, reliable, more closely mimicking the pathogenesis and clinical manifestation of neonatal HIE than models prepared with other methods, therefore, may be used in related research.
ABSTRACT
The evolution of infarction in the rat middle cerebral artery(MCA) occlusion model was examined by atomic absorption spectrometric measurements of Na, K and Ca concentrations in brain tissue sample. At 2, 4, 6, 8, and 24 hours after MCA occlusion and sham occlusion the brain tissue samples were obtained. Tissue water concentrations were estimated from dry-wet weight measurement. The effects of nimodipine(2 microgram/kg/min for 10 min) administered intra-venously at 4 hours(Group A), 6 hours(Group B), and 9 hours(Group C) after MCA occlusion were investigated on both the size of infarction and tissue water, Na, K, Ca concentrations at 24 hours. The result were as follows : 1) Normal concentrations of water, Na, K, and Ca averaged 0.793+/-0.009ml, 54.06+/-4.18 micromole, 81.04+/-3.44 micromole, and 3.578+/-0.712 micromole/gm wet weight. At the infarct site by 24 hours, the changes of tissue water and ionic concentrations were conspicuously evident so that water increased by more than 10%(p<0.005), Na increased by more than 120%(p<0.005), K decreased by more than 75%(p<0.005), and Ca increased by more than 200%(p<0.005). 2) The remarkable shifts of Na, K, and Ca concentrations occurred at 4-6 hours so that 60-85% of the ionic shifts developed by 6 hours. This characteristics of chronological ionic changes correlated well with the findings of 2% TTC staining during the evolution of infarction. Water concentrations increased rapidly at 2-4 hours so that nearly 80% of water shift developed by 4 hours. 3) In group A(administered at 4 hours), nimodipine treatment significantly reduced both the ionic shifts at the infarct site and the size of infarction compared with non-treated rats(p<0.05). 4) In group B(administered at 6 hours), nimodipine treatment did not significantly reduce the ionic shifts but did reduce the size of infarction compared with non-treated rats(p<0.05). In group C(administered at 8 hours), nimodipine treatment significantly reduce neither the ionic shifts nor the size of infarction. In summary it was concluded that the progressive changes in tissue water and ionic concentrations developed at the infarct sites and the critical period of the changes was between 4 and 6 hours, and nimodipine treatment was effective when administered within 4 hours. The results suggested that measurement of tissue ionic concentrations could be used as an alternative method for assessing tissue damage and a reliable method to quantify the tissue damage. This method may be useful for determining the time window for therapeutic protocol, as well as for evaluating therapeutic effects.