| Human serum albumin (HSA) is widely used in patients of head injury as a drug of dehydration. But whether albumin has direct neuroprotective, it is an important task at present. In many recent published of other countries, HSA, when administered in a high dose (2g/kg), has been proved to be markedly neuroprotective in models of both cerebral ischemia and traumatic brain injury (TBI)[1]. The purpose of this study is to determine whether treatment with high dose HAS would protect in a rat model of TBI. Objective:To investigate the effect of dose-response of albumin on severe fluid-percussion brain injury in rats and find out the effective dose of albumin. Methods:The studies were performed using fasted male Sprague-Dawley rats weighing between 250 g and 350 g. Anesthesia was induced by 2% pentobarbital (54mg/kg), and rat was positioned in a stereotaxic frame. A 4.8-mm craniotomy was made over the left parietal cortex (3.8-mm posterior to bregma and 2.5-mm lateral to midline). Next, a plastic injury tube was positioned over the exposed dura mater and bonded to surrounding structures by using dental acrylic. The animal was returned to its cage and allowed to recover overnight.The following day, rats were reanesthetized with ether. A fluid percussion device was connected to the injury tube of the rat's skull. Injury was induced by the descent of a pendulum, conveying a pressure transient of 2.0-2.1 atm to the left dorsolateral parietalcortex.The study consisted of four treatment groups. Within thirty minutes after trauma, rats in group 1, 2. 3, 4. respectively received 20% human serum albumin 2g/kg, 1.2g/kg, 0.8g/kg, 0.4g/kg, which were administered intravenously.Behavioral function was evaluated in 48 rats before and after TBI (1-7 day). Behavioral testing consisted of three tests: beam walking test, beam balance test, memory test.Tissue water content was measured by the dry-wet method 48 hours after injury. The tissue samples of 48 rats were weighed on a chemical balance to obtain the wet weight (W). The tissue samples were dried in a dessicating oven at 100℃ for 24 hours and weighed again to obtain the dry wet (D). The water content, expressed in liters per kilogram wet tissue weight, were calculated as (W-D)/W×100%.2 rats were sacrificed to take out hippocampus for pathological slice and electronic microscope to observe the neurons change in each group at 48 hours and 15days after injury.Side-effects were observed, including skin eruption, lesions of heart, lung, liver, kidney 30 days after injury. Results:Since the third day after trauma, the result of beam walking test of group 1 was better than the other groups' (P<0.01, figure 1). Since the second day after trauma, the result of beam balance test of group 1 was better than the other groups' (P<0.01, figure 2). Since the fourth day after trauma, the result of memory test of group 1 was better thanthe other groups' (P<0.01, figure 3).The tissue water content was respectively 78.09±0.42% (group 1),79.01±0.66% (group 2),78.89±0.45%(group 3), and79.03±0.35%( group 4).There was significant difference between group 1 and the other groups (P<0.01 figure 4).Pathological changes: in group 2, group 3 and group 4, part of hippocampus had unreversible changes. Acidophilus neurons had decreased size, nissl body disappeared, mitochondrion vacuolated, chromatin dissolved in nucleus. In group 1, organell had less swelling, endoplasmic reticulum, ribosome mitochondrial cristae, chromatin remained. Conclusion:The present results taken together with the previous evidence of neuroprotection indicate that human albumin may represent a highly desirable modality for treating acute TBI. In future studies, we shall define the therapeutic window of this treatment effect and explore the precise mechanisms of albumin-associated cytoprotection. |
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