Effects of ligustrazine on somatosensory evoked potential in normal rabbits and rabbits with cerebral ischemia-reperfusion injury

BACKGROUND： Somatosensory evoked potential （SEP） has become a method with higher sensitivity and specificity than electroencephalogram in detecting the brain function and the region, range and degree of ischemia. However, the effects of ligustrazine on SEP is still not clear. OBJECTIVE ： To study the protective effects of ligustrazini injection on cerebral ischemia-reperfusion injury.DESIGN： Auto-control study, random grouping.SETTING： Qilu Hospital of Shandong University.MATERIALS： The experiment was completed in the Cerebral Functional Room of Qilu Hospital Affiliated to Shandong University from March 2002 to June 2004. A totally of 24 healthy Harbin rabbits were randomly divided into blank control group （n=8）, model control group （n=8） and ligustrazine treatment group （n=8）. Hydrochloric ligustrazine injection, 40 mg/2 mL each ampoule, was provided by the Third Pharmaceutical Factory of Beijing （certification： 93035236273）. The main component was hydrochloric ligustrazine and the chemical name was 2, 3, 5, 6-tetramethyl pyrazine hydrochloride. METHODS：① Modeling method： The bilateral common carotid artery ligation was adopted to make the model. ② Index of cerebral functional lesion evaluated with SEP during ischemia-reperfusion： DISA 2000C neuromyoeletrometer provided by Dantec Electronics Ltd, Denmark was used to detect SEP. ③ Interventional process： Blank control group： The latencies and amplitudes of SEP were measured before injection with 1.5 mg/kg ligustrazine and at the points of 15 minutes, 20 minutes, 30 minutes, 60 minutes, 90 minutes and 120 minutes after injection. Ligustrazine treatment group： Rabbits were injected with 1.5 mg/kg ligustrazine, and those of model control group were injected the same volume of saline. Thirty minutes later, the bilateral common carotid artery of the rabbits all had been ligated for 30 minutes, and then reperfused for 120 minutes. The latencies and amplitudes of SEP were measured before injection, before ligation, at the points of 1 minute, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes and 30 minutes after ligation, and at the points of 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 60 minutes, 90 minutes and 120 minutes after reperfusion.④ Evaluating criteria： Normal values of P-wave latencies and amplitudes were （19.34±3.18） ms and （4.55±1.43）μV. Average value before injection in blank control group and average values before injection, after injection and before ligation in ischemiareperfusion group were regarded as control criteria to evaluate changes of P-wave latencies and amplitudes after experiment. MAIN OUTCOME MEASURES： P-wave latencies and amplitudes of SEP in the three groups.RESULTS ： A total of 24 rabbits were involved in the final analysis without any loss.① Blank control group： The P-wave latencies delayed markedly at each time point after injection. Compared with that before injection, there was a significant difference （P 〈 0.05-0.01）. The P-wave amplitudes did not fluctuate noticeably all the time after injection, but significantly decreased when compared with those before injection （P 〈 0.05-0.01）. ② Ischemia-reperfusion group： The P-wave latencies delayed and amplitudes decreased in the rabbits with cerebral ischemia-reperfusion at all points of time during cerebral ischemia-reperfusion, and there was significant difference when compared with the levels before ischemia （P 〈 0.05）. When ligustrazine was injected, the latencies and amplitudes changed less, and as compared with the levels before ischemia, the difference was not significant （P〉 0.05）.CONCLUSION：① Ligustrazine can inhibit P-wave latencies and amplitudes of SEP of normal rabbits.②Ligustrazine can improve P-wave latencies and amplitudes of SEP of rabbits with cerebral ischemia-reperfusion injury.

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.