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BACKGROUND: It has been confirmed that c-fos expression increased markedly in hypothalamic paraventricular nucleus (PVN) during asthmatic attack in rats, and PVN has extensive physiological functions, involving in the regulation of respiratory system, etc. OBJECTIVE: To observe the alteration of electroencephalogram (EEG) and power spectra in PVN during the asthmatic attack, and the alteration of lung function and diaphragmatic muscle discharge after bilateral PVN lesion in asthmatic rats. DESIGN: A randomized control study. SETTING: Laboratory of Physiology and Pharmacology, School of Basic Medical Sciences, Southeast University. MATERIALS: Forty-eight male adult SD rats of 260-300 g were used. The rats were randomly divided into 6 groups(n =8): control group, asthma group, electrolytic lesion of PVN group, KA-induced lesion of PVN group, sham electrolytic lesion of PVN group and sham kainic acid (KA)-induced lesion of PVN group. KA, chicken ovalbumin and aluminum hydroxide were purchased from American Sigma Company. Bordetella pertussis vaccine (Institute of Biological Products of Shanghai); stereotaxic apparatus (Jiangwan Ⅱ, China); lesion-producing device (YC-2 programmable stimulato, Chengdu Instrument Company); MD2000 signal processing system (Nanjing Medical School); data acquisition system (RM6240B, Chengdu Instrument Company). METHODs: The experiments were carried out in the Laboratory of Physiology and Pharmacology, School of Basic Medical Sciences, Southeast University from January to August in 2006. ① Rats except for control group were sensitized with an intraperitoneal injection of 100 mg chicken ovalbumin and 100 mg aluminum hydroxide and Bordetella pertussis vaccine containing 5×109 heat-killed in 1 mL of sterile saline. From the fifteenth to seventeenth days rats received three times aerosolized ovalbumin challenge. In rats of the control group and asthma group three steel electrodes were placed into the left PVN (AP -1.8 mm, LR 0.4 mm, OH -7.9 mm), parietal cortex and subcutaneous tissue in lower limb. Lung function tests were carried out simultaneously. Small holes were drilled in the skull to introduce a concentric bipolar electrode in the direction of the PVN in order to perform electrolytic lesion. The electrodes were connected to a lesion-producing device and a current of 1.0 -1.5 mA was passed over a period of 10-15 s on each side of the PVN. The rats received 0.5 μg/0.5 μL of KA in phosphate buffer (0.1 mol/L, pH 7.4), and the speed of infusion was 0.1 μL per minute in order to perform KA-induced lesion of PVN. ② Three days after operation of lesion, lung function tests were carried out. All the electrode and transducer were connected with data acquisition system. This technique yielded airway resistance (Raw), dynamic compliance (Cdyn), the expiratory time (Te)/the inspiratory time (Ti), minute ventilation volume (MVV), EMGdi frequency and EMGdi integral. ③The differences of the measurement data were compared using the t test. MAIN OUTCOME MEASURES: ① The alteration of EEG and power spectrum of PVN during asthmatic attack in sensitized rats; ② The effects of electrolytic lesion or KA-induced lesion of PVN on lung function in asthmatic rats. RESULTS: All the 48 rats were involved in the analysis of results. ① Alteration of EEG and power spectrum: Five minutes after injection of ovalbumin into caudal vena, the breathing rate of the rat was obviously speeded up and the total power spectrum was increased [(18 476.71±2 140.94), (13 838.75±2 983.26) mV2, P < 0.01], the percentage of the δ power and θ power decreased significantly (P < 0.01), while the percentage of α power and β1 power were enhanced (P < 0.05, 0.01). Ten minutes after injection, the EEG power spectrum of PVN further shifted rightward, the total power gradually increased (P < 0.01) which suggesting that the intensive hypersynchrony activities of PVN neurons. The percentage of δ power was decreased significantly (P < 0.01), but the α, β1 and β2 were increased (P < 0.01). Twenty-five minutes later, the breathing movements became steady, and the EEG power spectrum of PVN returned to the control level step by step. ② The alteration of lung function was detected during asthmatic attack after electrolytic lesion or KA-induced lesions of PVN respectively. It was found that EMGdi frequency, Te/Ti and RL were all decreased (P < 0.01), EMGdi integral, MVV and Cdyn were all enhanced (P < 0.01), while there were no significant changes in the sham surgery group (P > 0.05). CONCLUSION: The excitability of PVN is increased during the asthmatic attack. PVN plays a key role in the regulation of asthma. Both electrolytic and KA lesions of PVN can significantly relieve the asthmatic symptoms of rats, and improve their lung function.
BACKGROUND: It has been confirmed that c-fos expression increased markedly in hypothalamic paraventricular nucleus (PVN) during asthmatic attack in rats, and PVN has extensive physiological functions, involving in the regulation of respiratory system, etc. OBJECTIVE: To observe the alteration of electroencephalogram (EEG) and power spectra in PVN during the asthmatic attack, and the alteration of lung function and diaphragmatic muscle discharge after bilateral PVN lesion in asthmatic rats. Medical Sciences, Southeast University. MATERIALS: Forty-eight male adult SD rats of 260-300 g were used. The rats were randomly divided into 6 groups (n = 8): control group, asthma group, electrolytic lesion of PVN group, KA -induced lesion of PVN group, sham electrolytic lesion of PVN group and sham kainic acid (KA) -induced lesion of PVN group. KA, chicken ovalbumin and aluminum hydroxide were purch ased from American Sigma Company. Bordetella pertussis vaccine (Institute of Biological Products of Shanghai); stereotaxic apparatus (Jiangwan II, China); lesion- producing device (YC-2 programmable stimulato, Chengdu Instrument Company); MD2000 signal processing system Methods: The experiments were carried out in the Laboratory of Physiology and Pharmacology, School of Basic Medical Sciences, Southeast University from January to August in 2006. ① Rats except for control group (RM6240B, Chengdu Instrument Company) were sensitized with an intraperitoneal injection of 100 mg chicken ovalbumin and 100 mg aluminum hydroxide and Bordetella pertussis vaccine containing 5 x 109 heat-killed in 1 mL of sterile saline. From the fifteenth to seventeenth days mice received three times aerosolized ovalbumin challenge. of the control group and asthma group three steel electrodes were placed into the left PVN (AP -1.8 mm, LR 0.4 mm, OH -7.9 mm),Small holes were drilled in the skull to introduce a concentric bipolar electrode in the direction of the PVN in order to perform electrolytic lesion. The electrodes were connected to a lesion -producing device and a current of 1.0 -1.5 mA was passed over a period of 10-15 s on each side of the PVN. The rats received 0.5 μg / 0.5 μL of KA in phosphate buffer (0.1 mol / L, pH 7.4) , and the speed of infusion was 0.1 μL per minute in order to perform KA-induced lesion of PVN. ② Three days after operation of lesion, lung function tests were carried out. All the electrode and transducer were connected with data acquisition system. The differential of the measurement data were compared using (CdV), dynamic compliance (Cdyn), the expiratory time (Te) / the inspiratory time (Ti), minute ventilation volume the t test. MAIN OUTCOME MEASURES: ① The alteration of EEG and power spectrum of PVN during asthmatic attack in sensitized rats; ② The effects of electrolytic lesion or KA-induced lesion of PVN on lung function in asthmatic rats. RESULTS: All the 48 rats were involved in the analysis of results. ① Alteration of EEG and power spectrum: Five minutes after injection of ovalbumin into caudal vena, the breathing rate of the rat was obviously speeded up and the total power spectrum was increased [(18 476.71 ± 2 P <0.01], the percentage of the δ power and θ power decreased significantly (P <0.01), while the percentage of α power and β1 power were enhanced (P <0.05, 0.01) .This suggests that the intensive hypersynchrony activities of PVN neurons. The percentage of δ power was decreased significantly (P <0.01) .Those minutes after injection, the EEG power spectrum of PVN further shifted rightward, the total power gradually increased 0.01), but the α, β1 and β2 were increased (P <0.01). Twenty-five minutes later, the breathing movement was steady, and the EEG power spectrum of PVN returned to the control level step by step. ② The alteration of lung function was detected during asthmatic attack after electrolysis It was found that EMGdi frequency, Te / Ti and RL were all decreased (P <0.01), EMGdi integral, MVV and Cdyn were all enhanced (P <0.01), while there were no Significant changes in the sham surgery group (P> 0.05). CONCLUSION: The excitability of PVN is increased during the asthmatic attack. PVN plays a key role in the regulation of asthma. Both electrolytic and KA lesions of PVN can significantly relieve the asthmatic symptoms of rats, and improve their lung function.