| Objective:To investigate argatroban's effect on brain edema in rats after intracerebral hemorrhage.Materials and Methods: A total of 40 male Sprague-Dawley rats,each weighing 300 to 350 g,were used for all experiments.Animals were divided into 5 groups randomly,as following groups of A,B,C,D,and E.The animals were anesthetized with an intraperitoneal injection of 10ï¼…chlorali hydras (350mg/100g) and then positioned in a stereotactic frame.A cranial burr hole (1 mm) was drilled on the right coronal suture 3.5 mm lateral to the midline.A needle was inserted stereotaxically into the fight caudate nucleus of the rat (coordinates:0.2 mm anterior,5.5 mm ventral, and 3.5 mm lateral to bregma).In A group,the rats received an infusion of 60 ul saline at a rate of 20 uL/min(n=8).In B group,the rats received an infusion of 50 ul autologous whole blood + 10 ul saline(n=8).In C group, the rats received an infusion of 50 ul autologous whole blood + 10 ul argatroban solution(0.5ug/ml,n=8).In D group,the rats received an infusion of 10 U thrombin in 50 ul saline + 10 ul saline(n=8).In E group, the rats received an infusion of 10 U thrombin in 50 ul saline+10 ul argatroban solution (0.5ug/ml,n=8). The needle was removed,and the skin incision was closed with suture after infusion.Behavioral test was performed at hours 6,12,24,and 48,and then the rats were decapitated for brain water content measurement. Hematoxylin and eosin staining was performed to examine brain histological changes.Results:(1) In C and E groups,the marks of defective neurologic function were significantly different from those of groups B and D (P<0.05),they were significantly decreased at hours 24,and 48h.(2) In B and D groups,the brain water content were significantly increased,and were significantly different from those of groups C, E, and A(P<0.05),there were no significant differentence between group B and D(P>0.05). (3) Observing the gestalt form. of the brain: in B and D groups,the right cerebral hemisphere swelled,the gyri extended ,the sulci become shallow;the changes of C and E groups were slighter;in A group the bilateral hemispheres were approximately symmetric.The hematom,which was irregularly spheroid or oval,could been viewed at the area of basal nucleus in the coronal slice. HE staining and observing by Light-microscope:in the rats of B group,the red cells were integrity, the brain edema and neural injury surrouding the hematoma could been observed,inflammatory cells transmigrated, the nervous tissues were loose, nerve cells and colloidal cells swelled, and in cell space there were vacuoles of different sizes and the cell space increased,the cell ballooning degeneration and necrosis could been observed.In B group,the brain tissues swelled and were loose around the injected area, inflammatory cells transmigrated,the changes of C and E groups were slighter. There were not obviously pathological changes in A group.Conclusions:(1) After cutting off the rat's tail,the autologous whole blood was injected stereotaxically into the right caudate nucleus of the rat,the way of establishing the model of intracerebral hemorrhage was simple,duplicate, reliable, and operative during the experiment.(2) Brain edema formation following thrombin ~ infusion confirmed the neurotoxicity of thrombin.(3) The same brain edema formation, after the autologous whole blood was injected into the rat brain,confirmed that the early edema following intracerebral hemorrhage was related to the neurotoxicity of thrombin.(4) Argatroban diminished the brain water content in the rats after an infusion of thrombin into the brain, it suggested that argatroban could relieved the the destruction of the brain.by inhibited the activity of the thrombin.(5) Argatroban diminished cerebral edema in the rats after an infusion of autologous whole blood into the brain,it suggested that the treatment of intracerebral hemorrhage with argatroban was effective,it also confirmed argatroban treat cerebral edema by inhibited the activity of the thrombin. |
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