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Thioperamide treats neonatal hypoxic-ischemic encephalopathy by postsynaptic H1 receptors

Neural Regeneration Research 2013年第19期8卷 1814-1822页

作者： Feiyong Jia Lin Du Yunpeng Hao Shicheng Liu Ning Li Huiyi Jiang Division of Pediatric Neurorehabilitation Department of Pediatrics Second Part of First Hospital of Jilin University

Thioperamide, a selective histamine H3 receptor antagonist, can increase histamine content in the brain, improve brain edema, and exert a neuroprotective effect. This study aimed to examine the mechanism of action of thioperamide during brain edema in a rat model of neonatal hypoxic ischemic encephalopathy. Our results showed that thioperamide significantly decreased brain water content and malondialdehyde levels, while significantly increased histamine levels and superoxide dismutase activity in the hippocampus. This evidence demonstrates that thioperamide could pre vent oxidative damage and attenuate brain edema following neonatal hypoxicischemic encepha Iopathy. We further observed that changes in the above indexes occurred after combined treatment of thioperamide with the H1 receptor antagonist, pyrilamine, and the H2 receptor antagonist, ci metidine. Experimental findings indicated that pyrilamine reversed the effects of thioperamide; however, cimetidine had no significant influence on the effects of thioperamide. Our present findings suggest that thioperamide can increase brain histamine content and attenuate brain edema and oxidative damage by acting in combination with postsynaptic H1 receptors in a rat model of neo natal hypoxicischemic encephalopathy.

关键词： neural regeneration thioperamide histamine histamine receptor antagonist cimetidine pyrilamineneonatal hypoxic-ischemic encephalopathy brain edema hippocampus malondialdehyde super-oxide dismutase grants-supported paper neuroregeneration

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histaminergic systems and sleep-wake regulation

Histaminergic systems and sleep-wake regulation

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中国药理学会第十次全国学术会议

作者： HONG Zong-yuan (Institute of Quantitative Pharmacology of Wannan Medical College,Wuhu 241002)

In CNS,histaminergic neurons originate from the tuberomammillary nuclei(TMN) of the posterior hypothalamus and project diffusely throughout the *** a neurotransmitter or neuromodulator,histamine exerts and regulates lots of brain functions via histamine receptors(HR),including sleep-wake regulation. Under physiological conditions,the histamine release in the frontal cortex(FrCx) of mice was higher during wake episodes than during sleep episodes,being positively correlated with the time spent in *** of orexin A,a waking neuropeptide,into the TMN of rats promptly increased wakefulness and histamine release from both the medial preoptic area and the FrCx,indicating that the arousal effect of orexin A depends on the activation of histaminergic ***,CGS21680,an adenosine A2A receptor agonist,may significantly induced sleep and inhibited histamine release from the FrCx,and the histamine release was negatively correlated with the amount of non-rapid eye movement sleep,suggesting that inhibition of histaminergic neurotransmission induces ***,the data from H R gene-knocked out mice indicate that H R was involved in the regulation of behavioral state transitions from non-rapid eye movement sleep to wakefulness and that the arousal effect of the HR antagonist completely depended on the activation of histaminergic systems through HR. These findings suggest that activation of the histaminergic system promotes wakefulness,and that inhibition of it induces sleep.

关键词： histamine histamine receptor sleep-wake regulation wakefulness

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Role of neuropeptide S in sleep-wake regulation

Role of neuropeptide S in sleep-wake regulation

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中国神经科学学会第十届全国学术会议

作者： Yi-Ping HOU Peng ZHAO Yu-Feng SHAO Xiang-Pan KONG Department of Neuroscience AnatomyHistology and EmbryologyKey Laboratory of Preclinical Study for New Drugs of Gansu ProvinceSchool of Basic Medical SciencesLanzhou University

Objective Neuropeptide S（NPS） is a newly identified neuromodulator located in the *** selectively binds with high affinity to its receptor（NPSR）,involving in the regulation of multiple central *** NPS-NPSR system is proposed as a new arousal ***,the effects of NPS on the architectures of sleep-waking states and the mechanisms involved remain *** study is to explore the effects and mechanisms of NPS-NPSR system on sleep-wake *** Firstly,the sleep-waking states and related EEG power spectra were defined by the electroencephalogram（EEG） and electromyogram（EMG） signal recordings during light-phrase（8:00-20:00 h） in freely moving rats following intracerebroventricular（i.c.v.） injection of NPS,and ex-vivo Fos immunohistochemistry was made to identify the potential neuronal targets for NPS in the brain involved in ***,according to primary results,the distribution of NPSR mRNA was revealed by quantitative real-time PCR（RT-PCR） and dual-immunofluorescences *** sleep-waking profiles following bilateral microinjections of NPS into the tuberomammillary nucleus（TMN） were studied for comprehensive understanding NPS-NPSR system in regulating sleep-wake ***,the neuropharmacology assays were made to identify whether the antagonists of NPSR,H1R and H2R receptors block the arousal effect of ***（1） Central administration of NPS（0.1-1 nmol）increased significantly wakefulness（W） during the first 2 h,accompanied by an increase in EEG high frequency activities（14.5-60 Hz）.In the meanwhile,slow wave sleep（SWS） and paradoxical sleep（PS） decreased significantly,and accompanied by a suppression in EEG delta（0.5-4 Hz） and theta（4.5-8.5 Hz） *** W-increasing effect was because of a significant increase in the mean duration of wake episode.（2） Fos immunohistochemistry in the posterior hypothalamus revealed that,as compared with saline-treated rats,NPS enhanced c-Fos expression in histaminergic n

关键词： neuropeptide S neuropeptide S receptor sleep-wake states tuberomammillary nucleus histaminergic neurons orexinergic neurons histamine receptor antagonist

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