Effect of cerebral lymphatic block on cerebral morphology and cortical evoked potential in rats

BACKGROUND: It has been shown that although brain does not contain lining endothelial lymphatic vessel, it has lymphatic drain. Anterior lymphatic system of lymphatic vessel in brain tissue plays a key role in introducing brain interstitial fluid to lymphatic system; however, the significance of lymphatic drain and the effect on cerebral edema remains unclear. OBJECTIVE: To investigate the effect of cerebral lymphatic block on cerebral morphology and cortical evoked potential in rats. DESIGN: Randomized controlled animal study. SETTING: Institute of Cerebral Microcirculation of Taishan Medical College and Department of Neurology of Affiliated Hospital. MATERIALS: A total of 63 healthy adult male Wistar rats weighing 300-350 g were selected in this study. Forty-seven rats were used for the morphological observation induced by lymphatic drain and randomly divided into three groups: general observation group (n =12), light microscopic observation group (n =21) and electronic microscopic observation group (n =14). The rats in each group were divided into cerebral lymphatic block subgroup and sham-operation control subgroup. Sixteen rats were used for observing the effect of cerebral lymphatic block on cortical evoked potential, in which the animals were randomly divided into sham-operation group (n =6) and cerebral lymphatic block group (n =10). METHODS: The experiment was carried out in the Institute of Cerebral Microcirculation of Taishan Medical College from January to August 2003. Rats in cerebral lymphatic block group were anesthetized and separated bilateral superficial and deep cervical lymph nodes under sterile condition. Superior and inferior boarders of lymph nodes were ligated the inputting and outputting channels, respectively, and then lymph node was removed so as to establish cerebral lymphatic drain disorder models. Rats in sham-operation control group were not ligated the lymphatic vessel and removed lymph nodes, and other operations were as the same as those in cerebral lymphatic block group. Morphological changes of the brain and alterations of latency of cortical evoked potential were detected on the 1st, 2nd, 3rd, 5th, 7th, 10th and 15th days after operation under general, light microscope and electronic microscope observations. MAIN OUTCOME MEASURES: ① Cerebral morphological changes; ② latent changes of cortical evoked potential. RESULTS: A total of 63 rats were involved in the final analysis. ① Cerebral morphological changes: General observation showed that, for cerebral lymphatic block rats, the surface of brain was pale and full, and cerebral gyrus was wide and flattened sulci after cerebral lymphatic block; and cerebral tissue space prolongation, increased interstitial fluid, neuronal degeneration and necrosis, diffused phagocytes and satellitosis were observed under light microscope. Neuronal swell and necrosis, glial cell swell, apparent subcellular changes such as mitochondron were observed under electronic microscope. ② Latent changes of cortical evoked potential: As compared with sham-operation control group, latency of cortical evoked potential in cerebral lymphatic blockage group prolonged on the 5th day and 7th day after cerebral lymphatic block [(6.28±0.23), (6.97±0.35) ms; (6.23±0.22), (7.12±0.20) ms; P < 0.01]. CONCLUSION: ① Cerebral lymphatic block plays an important role in cerebral morphology, and may result in abnormality of sensitive impulse conduction and prolong latency of cortical evoked potential. ② Examination of cortical evoked potential is easy and convenient, so it is regarded as a key index for lymphatic disturbed cerebral injury.