RESUMO
BACKGROUND: In recent years, there are many studies designed to explain the protective effect of lidocaine on brain, but few about the therapeutic effect on traumatic cerebral edema. The content of aquaporin-4(AQP-4) in brain tissue is the highest and it has been proved that AQP-4participants in the formation of cerebral edema induced by cerebral trauma, cerebral infarction, eerebrai tumor and other reasons.OBJECTIVE: To observe the effect of lidocaine on the expression of AQP-4 of experimental rats following brain injury and analyze the therapeutic effect of lidocaine on brain edema.DESIGN: A randomized and control animal experiment.SETTING: Department of Anesthesiology, Affiliated Hospital of Medical College of Qingdao University.MATERIALS: The experiment was carried out in the Institute of Brain Disease, the Medical School Hospital of Qingdao University between January and July 2004. Totally 65 three-month-old healthy male Wistar rats,were enrolled in the experiment and randomly divided into 3 groups: normal control group (n=5), model group (n=30) and treatment group (n=30). Thirty rats in the model group and treatment group were respectively assigned into 6 subgroups according to 6 different time points: 1,4,6,12,24 and 48 hours following brain injury, with 5 rats at each time point.METHODS: Animal models of brain injury at right parietal lobe were created according to the method from Feeney et al. As for the rats of normal control group, they only underwent operation to be injured at the corresponding part. Rats recovered the access to food and water 2 to 8 hours after operation. For the rats in the treatment group, they were intraperitoneally injected of lidocaine at the 1st, 4th,6th, 12th, 24th, and 48th hours following injury, 5 rats at each time point. The initial dosage was 30 mg/kg, then 15 mg/kg was maintained . Administration was conducted every 6 hours in 3 days; For the rats in the model group, they were intraperitoneally injected of 30 mg/kg normal saline and rats in the normal control group were given no special treatments. Water content of brain was calculated 5 days following brain injury with dry and wet weight method:water content of brain=[brain mass (wet)-brain mass (dry)]/brain mass(wet)×100%. Expression of AQP-4 of brain tissue of rats was detected with immunohistochemical method and cytomorphological change of brain tissue was observed under optical microscope.MAIN OUTCOME MEASURES: ① Water content of brain of rats in each group. ② Expression of AQP-4 of brain tissue of rats in each group.③ Pathological results of brain tissue of rats in each group.RESULTS: No rats died accidentally or for other factors in the process of experiment, finally, all the 65 rats entered the stage of result analysis. ①Compared with model group, administration of lidocaine within 6 hours following brain injury could significantly decrease the water content of brain tissue [1 hour after brain injury: (81.09±0.29)%, (83.04±0.25)% ,P ＜ 0.05];[4 hours after brain injury: (81.34±0.35)%, (83.31±0.48)%,P ＜ 0.05] ;[6 hours after brain injury: (82.01±0.21)%, (83.25±0.37)% ,P ＜ 0.05]. Compared with model group, administration of lidocaine could significantly decrease the expression of AQP-4 [1 hour after brain injury:(0.19±0.02), (0.24±0.03),P ＜ 0.05]; [4 hours after brain injury: (0.21±0.05 ), (0.25±0.05) ,P ＜ 0.05]; [6 hours after brain injury: (0.21±0.03 ),(0.24±0.02) ,P ＜ 0.05]. There were no significant differences of AQP-4expression and water content of brain tissue when administration was conducted at the 12th, 24th and 48th hours following brain injury (P ＞ 0.05). ②Under the microscope, AQP-4 positive cells presented vacuolus, they mainly lay in the edema area of peripheral part of trauma, cortex of traumatic side and around the blood vessel as well as astrocyte of white substance, choroid plexus and ependymal layer. ③ Necrosis was found in most cells in the central area of trauma and apoptosis in most cells in the peripheral area. Compared with model group, necrotic and apoptotic cells were significantly less within 6 hours following trauma, but not at the 12th,24th and 48th hours following trauma in the treatment group.CONCLUSION: High dosage of lidocaine can decrease the expression of AQP-4 and lighten cerebral edema following brain injury, but administration should be given as early as possible.
