That herbs with the"hot"property used to treat"cold"syndromes is a guiding principle of clinical prescription and medication in traditional Chinese medicine(TCM).However,this theory of TCM is still...That herbs with the"hot"property used to treat"cold"syndromes is a guiding principle of clinical prescription and medication in traditional Chinese medicine(TCM).However,this theory of TCM is still in the‘black box'stage,and few in-depth studies have examined the biological mechanisms underpinning the hot properties of herbs.展开更多
BACKGROUND Visceral hypersensitivity is the core pathogenesis of irritable bowel syndrome(IBS)and is often accompanied by negative emotions such as anxiety or depression.Paraventricular hypothalamic nucleus(PVN)cortic...BACKGROUND Visceral hypersensitivity is the core pathogenesis of irritable bowel syndrome(IBS)and is often accompanied by negative emotions such as anxiety or depression.Paraventricular hypothalamic nucleus(PVN)corticotropin-releasing factor(CRF)is involved in the stress-related gastrointestinal dysfunction.Electroacupuncture(EA)has unique advantages for the treatment of visceral hypersensitivity and negative emotions in IBS patients.However,the underlying mechanisms remain unclear.AIM To investigate the pathological mechanisms visceral hypersensitivity and negative emotions in IBS,as well as the effect mechanism of EA.METHODS A model of diarrhoeal IBS(IBS-D)with negative emotions was prepared by chronic restraint combined with glacial acetic acid enema.The effect of EA was verified by abdominal withdrawal reflex and open-field test.PVN CRFcolonic mast cell(MC)/transient potential receptor vanilloid type 1(TRPV1)pathway was detected by immunofluorescence,Western blot,ELISA,and toluidine blue staining.Moreover,PVN CRFergic neurons were activated or inhibited by chemogenetical technique to observe the changes of effect indicator.RESULTS In the model group,IBS-D symptoms and negative emotions were successfully induced.Notably,the combination of Baihui(GV20)with Tianshu(ST25)and Dachangshu(BL25)acupoints showed the greatest efficacy in improving the negative emotions and visceral hypersensitivity in model mice.Furthermore,we found that EA inhibited overactivated PVN CRFergic neurons and the overexpression of serum CRF,colonic CRF,CRF-receptor 1(CRFR1),mast cell tryptase(MCT),protease-activated receptor 2 and TRPV1 in model mice.Moreover,we found that activating PVN CRFergic neurons induced negative emotions and visceral hypersensitivity in normal mice;however,inhibiting PVN CRFergic neurons alleviated negative emotions and intestinal symptoms in model mice and decreased the expression of colonic CRF-R1,MCT,and TRPV1.CONCLUSION This research highlights the key role of PVN CRF-MC CRF-R1 and the downstream MC/TRPV1 pathway in the pathological process of IBS-D and the mechanism of the effect of EA.展开更多
BACKGROUND Type 2 diabetes mellitus(T2DM)is often accompanied by impaired glucose utilization in the brain,leading to oxidative stress,neuronal cell injury and inflammation.Previous studies have shown that duodenal je...BACKGROUND Type 2 diabetes mellitus(T2DM)is often accompanied by impaired glucose utilization in the brain,leading to oxidative stress,neuronal cell injury and inflammation.Previous studies have shown that duodenal jejunal bypass(DJB)surgery significantly improves brain glucose metabolism in T2DM rats,the role and the metabolism of DJB in improving brain oxidative stress and inflammation condition in T2DM rats remain unclear.AIM To investigate the role and metabolism of DJB in improving hypothalamic oxidative stress and inflammation condition in T2DM rats.METHODS A T2DM rat model was induced via a high-glucose and high-fat diet,combined with a low-dose streptozotocin injection.T2DM rats were divided into DJB operation and Sham operation groups.DJB surgical intervention was carried out on T2DM rats.The differential expression of hypothalamic proteins was analyzed using quantitative proteomics analysis.Proteins related to oxidative stress,inflammation,and neuronal injury in the hypothalamus of T2DM rats were analyzed by flow cytometry,quantitative real-time PCR,Western blotting,and immunofluorescence.RESULTS Quantitative proteomics analysis showed significant differences in proteins related to oxidative stress,inflammation,and neuronal injury in the hypothalamus of rats with T2DM-DJB after DJB surgery,compared to the T2DM-Sham groups of rats.Oxidative stress-related proteins(glucagon-like peptide 1 receptor,Nrf2,and HO-1)were significantly increased(P<0.05)in the hypothalamus of rats with T2DM after DJB surgery.DJB surgery significantly reduced(P<0.05)hypothalamic inflammation in T2DM rats by inhibiting the activation of NF-κB and decreasing the expression of interleukin(IL)-1βand IL-6.DJB surgery significantly reduced(P<0.05)the expression of factors related to neuronal injury(glial fibrillary acidic protein and Caspase-3)in the hypothalamus of T2DM rats and upregulated(P<0.05)the expression of neuroprotective factors(C-fos,Ki67,Bcl-2,and BDNF),thereby reducing hypothalamic injury in T2DM rats.CONCLUSION DJB surgery improve oxidative stress and inflammation in the hypothalamus of T2DM rats and reduce neuronal cell injury by activating the glucagon-like peptide 1 receptor-mediated Nrf2/HO-1 signaling pathway.展开更多
Objective:This study investigates the sleep-modulating effects of ginsenoside Rg1(Rg1,C_(42)H_(72)O_(14)),a key bioactive component of ginseng,and elucidates its underlying mechanisms.Methods:C57BL/6J mice were intrap...Objective:This study investigates the sleep-modulating effects of ginsenoside Rg1(Rg1,C_(42)H_(72)O_(14)),a key bioactive component of ginseng,and elucidates its underlying mechanisms.Methods:C57BL/6J mice were intraperitoneally administered doses of Rg1 ranging from 12.5 to100 mg/kg.Sleep parameters were assessed to determine the average duration of each sleep stage by monitoring the electrical activity of the brain and muscles.Further,orexin neurons in the lateral hypothalamus(LH)and corticotropin-releasing hormone(CRH)neurons in the paraventricular hypothalamic nucleus(PVH)were ablated using viral vector surgery and electrode embedding.The excitability of LH^(orexin)and PVH^(CRH)neurons was evaluated through the measurement of cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog(c-Fos)expression.Results:Rg1(12.5–100 mg/kg)augmented the duration of non-rapid eye movement(NREM)sleep phases,while reducing the duration of wakefulness,in a dose dependent manner.The reduced latency from wakefulness to NREM sleep indicates an accelerated sleep initiation time.We found that these sleep-promoting effects were weakened in the LH^(orexin)and PVH^(CRH)neuron ablation groups,and disappeared in the orexin and CRH double-ablation group.Decreased c-Fos protein expression in the LH and PVH confirmed that Rg1 promoted NREM sleep by inhibiting orexin and CRH neurons.Conclusion:Rg1 increases the duration of NREM sleep,underscoring the essential roles of LH^(orexin)and PVH^(CRH)neurons in facilitating the sleep-promoting effects of Rg1.Please cite this article as:Wang YY,Wu Y,Yu KW,Xie HY,Gui Y,Chen CR,Wang NH.Ginsenoside Rg1 promotes non-rapid eye movement sleep via inhibition of orexin neurons of the lateral hypothalamus and corticotropin-releasing hormone neurons of the paraventricular hypothalamic nucleus.J Integr Med.2024;22(6):719–728.展开更多
Objective To study the central role of ginkgolide B （BN52021） in regulating cardiovascular function of nerve center by examining the effects of ginkgolide B on the electrical activity of rat paraventricular nucleus ...Objective To study the central role of ginkgolide B （BN52021） in regulating cardiovascular function of nerve center by examining the effects of ginkgolide B on the electrical activity of rat paraventricular nucleus （PVN） neurons in hypothalamic slice preparation and to elucidate the mechanism involved. Methods Extracellular single-unit discharge recording technique. Results （1） In response to the application of ginkgolide t3 （0.1, 1, 10 μmol/L; n = 27） into the perfusate for 2 rain, the spontaneous discharge rates （SDR） of 26 （26/27, 96.30%） neurons were significantly decreased in a dose-dependent manner. （2） Pretreatment with L-glutamate （L-Glu, 0.2 mmol/L） led to a marked increase in the SDR of all 8 （100%） neurons in an epileptiform pattern. The increased discharges were suppressed significantly after ginkgolide B （1 μmol/L） was applied into the perfusate for 2 min. （3） In 8 neurons, perfusion of the selective L-type calcium channel agonist, Bay K 8644 （0.1 μmol/L）, induced a significant increase in the discharge rates of 8 （8/8, 100%） neurons, while ginkgolide B （1μmol/L） applied into the perfusate, could inhibit the discharges of 8 （100%） neurons. （4） In 8 neurons, the broad potassium channels blocker, tetraethylammonium （TEA, 1 mmol/L） completely blocked the inhibitory effect of ginkgolide B （1 μmol/L）. Conclusion These results suggest that ginkgolide B can inhibit the electrical activity of paraventricular neurons. The inhibitory effect may be related to the blockade of L-type voltage-activated calcium channel and potentially concerned with delayed rectifier potassium channel （KDR）.展开更多
The lateral hypothalamic area(LHA)plays a pivotal role in regulating consciousness transition,in which orexinergic neurons,GABAergic neurons,and melanin-concentrating hormone neurons are involved.Glutamatergic neurons...The lateral hypothalamic area(LHA)plays a pivotal role in regulating consciousness transition,in which orexinergic neurons,GABAergic neurons,and melanin-concentrating hormone neurons are involved.Glutamatergic neurons have a large population in the LHA,but their anesthesia-related effect has not been explored.Here,we found that genetic ablation of LHA glutamatergic neurons shortened the induction time and prolonged the recovery time of isoflurane anesthesia in mice.In contrast,chemogenetic activation of LHA glutamatergic neurons increased the time to anesthesia and decreased the time to recovery.Optogenetic activation of LHA glutamatergic neurons during the maintenance of anesthesia reduced the burst suppression pattern of the electroencephalogram(EEG)and shifted EEG features to an arousal pattern.Photostimulation of LHA glutamatergic projections to the lateral habenula(LHb)also facilitated the emergence from anesthesia and the transition of anesthesia depth to a lighter level.Collectively,LHA glutamatergic neurons and their projections to the LHb regulate anesthetic potency and EEG features.展开更多
AIM： To investigate the effects of electrical stimulation of hypothalamic paraventricular nuclei （PVN） on gastric mucosal cellular apoptosis and proliferation induced by gastric ischemia/reperfusion （I/R） injury....AIM： To investigate the effects of electrical stimulation of hypothalamic paraventricular nuclei （PVN） on gastric mucosal cellular apoptosis and proliferation induced by gastric ischemia/reperfusion （I/R） injury. METHODS： For different experimental purposes, stimulating electrode plantation or electrolytic destruction of the PVN was applied, then the animals＇ GI/R injury model was established by clamping the celiac artery for 30 min and allowing reperfusing the artery for 30 rain, 1 h, 3 h or 6 h respectively. Then histological, immunohistochemistry methods were used to assess the gastric mucosal damage index, the gastric mucosal cellular apoptosis and proliferation at different times. RESULTS： The electrical stimulation of PVN significantly attenuated the GI/R injury at 30 min, i h and 3 h after reperfusion. The electrical stimulation of PVN decreased gastric mucosal apoptosis and increased gastric mucosal proliferation. The electrolytic destruction of the PVN could eliminate the protective effects of electrical stimulation of PVN on GI/R injury. These results indicated that the PVN participated in the regulation of GI/R injury as a specific area in the brain, exerting protective effects against the GI/R injury, and the protection was associated with the inhibition of cellular apoptosis and the promotion of gastric mucosal proliferation. CONCLUSION： Stimulating PVN significantly inhibits the gastric mucosal cellular apoptosis and promots gastric mucosal cellular proliferation. This may explain the protective mechanisms of electrical stimulation of PVN against GI/R injury.展开更多
OBJECTIVE:To explore whether the paraventricular nucleus(PVN)participates in regulation of the antimyocardial ischemia-reperfusion injury(MIRI)effect of electroacupuncture(EA)and whether this is achieved through the P...OBJECTIVE:To explore whether the paraventricular nucleus(PVN)participates in regulation of the antimyocardial ischemia-reperfusion injury(MIRI)effect of electroacupuncture(EA)and whether this is achieved through the PVN-interposed nucleus(IN)neural pathway.METHODS:The modeling method of myocardial ischemia reperfusion injury was achieved by ligating the left anterior descending coronary artery in SpragueDawley rats.We used the Powerlab multi-channel physiological recorder system to record electrocardiograms and analyze the changes in ST segment displacement;2,3,5-Triphenyltetrazolium chloride staining was used to observe the percentage of myocardial infarction areas.Detecting cardiac troponin I(cTnI),lactate dehydrogenase(LDH)in serum was done with an enzyme-linked immunosorbent assay kit.Morphological changes in the myocardium were detected in each group with hematoxylin-eosin staining of paraffin sections.Detection of c-fos protein expression in the PVN of the hypothalamus was done with the immuneofluorescence method.The Plexon multi-channel acquisition system recorded PVN neuron discharges and local field potentials in each group of rats.Offline Sorter software was used for cluster analysis.Neuro Explorer software was used to perform autocorrelation,raster and frequency characteristics and spectral energy analysis of neuron signals in each group.RESULTS:Compared with the MIRI model group,the areas of myocardial infarction in the EA group were significantly reduced;the expression of cTnI,LDH in serum was decreased significantly.The firing frequency of pyramidal cells in the PVN was significantly increased and the spectrum energy map showed energy was reduced,c-fos expression in PVN was reduced,this indicated that neuronal activity in the PVN participates in the effect of EA improving myocardial injury.In addition,we used the kainic acid method to lesion the IN and observed that the effect of EA was weakened.For example,the area of myocardial infarction of lesion IN+EA group in rats was significantly increased compared with that resulting from EA group,the expression of cTnI,LDH in serum was significantly increased,the firing frequency of pyramidal cells in the PVN was significantly reduced.A spectral energy diagram shows that the energy after damage was higher than that of EA group.At the same time,the expression of c-fos in the PVN increased again.CONCLUSION:Our results indicated that the PVN-IN nerve pathway may participate as an effective pathway of EA to improve the effect of myocardial injury.展开更多
AIM: To determine the expression levels of gastrointestinal nesfatin-1 in ventromedial hypothalamic nucleus (VMH)-lesioned (obese) and ventrolateral hypothalamic nucleus (VLH)-lesioned (lean) rats that exhibit an imba...AIM: To determine the expression levels of gastrointestinal nesfatin-1 in ventromedial hypothalamic nucleus (VMH)-lesioned (obese) and ventrolateral hypothalamic nucleus (VLH)-lesioned (lean) rats that exhibit an imbalance in their energy metabolism and gastric mobility.展开更多
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 regu...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(JiangwanⅡ,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 2006.①Rats 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 5×10^(9) 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 0.5μg/0.5μL of KA in phosphate buffer(0.1 mol/L,pH 7.4),and the speed of infusion was 0.1μL per minute in order to perform KA-induced lesion of PVN.②Three 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:①The alteration of EEG and power spectrum of PVN during asthmatic attack in sensitized rats;②The 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.①Alteration 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[(18476.71±2140.94),(13838.75±2983.26)mV^(2),P<0.01],the percentage of theδpower andθpower decreased significantly(P<0.01),while the percentage ofαpower andβ1 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 ofδpower was decreased significantly(P<0.01),but theα,β1 andβ2 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.②The 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.展开更多
Objective. To explore an effective method of surgical management of craniopharyngioma. Subjects and methods. Fifty patients with craniopharyngioma had total andsubtotal tumor ectomy. There were 29 males and 21 females...Objective. To explore an effective method of surgical management of craniopharyngioma. Subjects and methods. Fifty patients with craniopharyngioma had total andsubtotal tumor ectomy. There were 29 males and 21 females, ranging in age from 15 to 56 years (mean 34.1 years). MR imaging showed that the tumors were locatedin the superior sellar region in 24 cases, in superior sella region and extended into the third ventricular floor in 19 cases, into parasella in 3 cases and down to intrasella in 4 cases. Complete cystic tumors were found in 5 cases, whilethe partial cystic tumor in 24 cases and complete solid tumors in 21 cases. Pterional approach was used in 48 patients and subfrontal approach in 2 patients. Great attention was paid to the preservation of the perforating arteries from thecarotid, posterior and anterior communicating and anterior choroidal arteries to the hypothalamic structures. The clinical outcome was evaluated according to the GOS scale.Results. Of the 50 patients surgically treated, 47 patients obtained total ectomy of the tumor and 3 patients with the secondary surgery had subtotal ectomy of the tumor. The pituitary stalk was preserved in 29(58%) patients, severed in 14 patients and unidentified in 7 patients. Forty-six patients regained a normal life; one patient needed assist in life. Of the 3 deaths, one patient died of diabetes insipidus, one of inhalation asphyxia, and another one of water and sodium disorders. Conclusion. Avoidance of the injury to the neural structures in the thirdventricular floor and preservation of the perforating arteries to hypothalamus are the key to achieve good surgical results in treating craniopharyngioma.展开更多
OBJECTIVES： An animal experiment clarified that insertion of an orthodontic apparatus activated the trigeminal neurons of the medulla oblongata. Orthodontic tooth movement is known to be associated with the sympathet...OBJECTIVES： An animal experiment clarified that insertion of an orthodontic apparatus activated the trigeminal neurons of the medulla oblongata. Orthodontic tooth movement is known to be associated with the sympathetic nervous system and controlled by the nucleus of the hypothalamus. However, the transmission of both has not been demonstrated in humans. The purpose of this study were to examine the activated cerebral areas using brain functional magnetic resonance imaging（MRI）, when orthodontic tooth separators were inserted, and to confirm the possibility of the transmission route from the medulla oblongata to the hypothalamus.METHODS： Two types of alternative orthodontic tooth separators（brass contact gauge and floss） were inserted into the right upper premolars of 10 healthy volunteers. Brain functional T2＊-weighted images and anatomical T1-weighted images were taken.RESULTS： The blood oxygenation level dependent（BOLD） signals following insertion of a brass contact gauge and floss significantly increased in the somatosensory association cortex and hypothalamic area.CONCLUSION： Our findings suggest the possibility of a transmission route from the medulla oblongata to the hypothalamus.展开更多
Objective.. To compare the mechanisms of analgesia induced by four kinds of acupunture therapies at the trypothalamic level in adjuvant arthritic rats. Methods： Forty-eight SD rats were randomized into normal, model,...Objective.. To compare the mechanisms of analgesia induced by four kinds of acupunture therapies at the trypothalamic level in adjuvant arthritic rats. Methods： Forty-eight SD rats were randomized into normal, model, electroacupuncture （EA）, filiform needle （FN）, pricking blood-letting （BL） and point injection （PI） groups, with 8 cases in each. EA （20-100 Hz, 2-4 V and duration of 20 min）, FN, BL PI were respectively applied to “Kunlun” （昆仑 BL 60）. Arthritis model was established by injecting complete Freund＇s adjuvant （0.1 mL） into the rat＇s right foot pad. Behavioral reactions, pain threshold （latancy of tail flick to heat stimulation） and local swelling severity （foot volurne） were detected; the cordents of β-endorphin （β-EP） and α- drenocortiootropin （ACTH） were assayed with radioimmunoassay; and the expression of pro-opi-omelanocortin （POMC） mRNA in hypot were determined with hybridization method. Results： The pain threshold was significantly enhanced by all the four kinds of acupuncture therapies, and the effects of EA and PI were more obvious （P〈0.05, P〈0.01）. The severity of local swelling was markedly alleviated by all the four kinds of acupuncture therapies （ P〈 0.01 ） without significant differences among them （P 〉 0.05）. The content of β-EP in the hypothalamus was obviously elevated by EA and FN （P〈 0.05, P 〈 0.01 ）, and the effect of EA was more obvious, but no marked effect of BL or PI on β-EP was found （ P 〉0.05）. The content of ACTH in hypothalamus was considerably elevated by PI （P〈0.05）, but not by the other three therapies. The expression of PCMCmRNA in hypothalamus was significantly strengthened by EA and FN （P〈0. 01）, but not by the other two therapies. Conclusion：EA, flliform needle, blood-letting and point-injection all can produce analgesic effect in adjuvant arthritis rats, the effect of EA and filiform needie may be related to their resultant increase of hypothalamic β-EP, and that of point-injectiON related to the increase of hypothalamic ACTH level.展开更多
Hypothalamic Corticotropin-releasing factor (CRF) directly activates the hypothalamic pituitary adrenal axis (HPA axis) during the surgical trauma induced stress response. Electroacupuncture (EA) has been demonstrated...Hypothalamic Corticotropin-releasing factor (CRF) directly activates the hypothalamic pituitary adrenal axis (HPA axis) during the surgical trauma induced stress response. Electroacupuncture (EA) has been demonstrated to have stress relieving effects in breast surgery, colorectal surgery, prostatectomy and craniotomy. This study was aimed to investigate the hypothesis that EA could regulate hypothalamic CRF in surgical trauma rats. In experiment one, Sprague-Dawley (SD) male rats were divided into intact, model (10% partial hepatectomy), sham EA and EA group. Rats from the Sham EA and EA group were stimulated at ST36-Zusanli and SP6-Sanyiniiao acupoints twice, 24 hours before the surgery and immediately after the surgery. Expressions of hypothalamic CRF and CRFR, GABA receptors, glutamate decarboxylase (GAD), serum adrenocorticotropic hormone (ACTH) and Corticosterone (CORT) were observed at 2, 4, 8 and 24 h after the surgery by radioimmunoassay (RIA), western blot, real-time PCR and immunohistochemistry. In the experiment two, SD male rats were divided into the intact, model, model + vehicle, model + L-838,417 EA and EA + L838,417 group. It was found that hypothalamus CRF, serum ACTH and CORT levels were increased in model group compared with the intact group, and those in the EA group decreased in comparison with the model group. Compared with the model group, hypothalamus-aminobutyric acid (GABA) receptor Aα3 mRNA and protein expressions of the EA group raised strikingly. In conclusion, EA alleviated surgical stress response by improving the GABA synthesis in hypothalamus, thus enhancing GABA receptors’ inhibitory regulation of the HPA axis dysfunction in rats with acute surgical trauma.展开更多
<div style="text-align:justify;"> <span style="font-family:Verdana;">The study of interactions between neuroendocrinology and immunology, or immunoendocrinology, is a recent field with ...<div style="text-align:justify;"> <span style="font-family:Verdana;">The study of interactions between neuroendocrinology and immunology, or immunoendocrinology, is a recent field with the majority of its development in the last 30 years that involves communication between the nervous, endocrine, and immune systems. Homeostasis, development, aging, metabolism, infection, and inflammation are all influenced by the cross talk between these systems via hormones, cytokines, and neurotransmitters. The nervous system affects the immune system through either the hypothalamus-pituitary axes (adrenal, gonadal, thyroid, growth-hormone) neuropeptide and hormone signals or autonomic nervous system signals of norepinephrine and acetylcholine. On the other hand, the immune system passes feedback through cytokine type and concentration in the blood. Imbalance of any of these systems leads to increased risk in severity of metabolic, psychiatric, inflammatory or autoimmune diseases. These two systems are complex standalone and even more so in their interaction. Thus, the relationship between the immune system and the hypothalamus-pituitary-thyroid axis is necessary to be reviewed.</span> </div>展开更多
The effects of somatostatin and cysteamine injected into theventromedial nucleus of hypothalamus(VMH)on somatostatin-likeimmunoreactivity(SLI)concentration in the gastric antral mucosa and portal veinplasma,as well as...The effects of somatostatin and cysteamine injected into theventromedial nucleus of hypothalamus(VMH)on somatostatin-likeimmunoreactivity(SLI)concentration in the gastric antral mucosa and portal veinplasma,as well as the gastric acid secretion were studied in anesthetized rats.TheSLI concentration in the gastric antral mucosa and portal vein plasma and thegastric acid output were significantly increased one hour after the injection ofsomatostatin(0.5μg/0.5μ1)into the VMH.Four hours later,the SLI concentrationin the mucosa was still higher than the control level,while the SLI level in theplasma and the acid secretion were close to those of controls.On the contrary,the SLI concentration in the mucosa and plasma and the acid output weremarkedly decreased at four hours after the injection of cysteamine(15μg/0.5μ1)into the VMH.The present results suggest that both exogenous and endogenoussomatostatin in the VMH have a facilitatory action on the gastric somatostatinconcentration and its release as well as on the gastric acid secretion,thus provid-ing evidence for hypothalamic control of gastric somatostatin and acid secretion.展开更多
Extracellular discharges of neurons in the dorsomedial nucleus（DMN）were recordedwith glass microelectrode from rat hypothalamic slices.The firing frequency decreased in 77 andincreased in 48 units during the additio...Extracellular discharges of neurons in the dorsomedial nucleus（DMN）were recordedwith glass microelectrode from rat hypothalamic slices.The firing frequency decreased in 77 andincreased in 48 units during the addition of norepinephrine into the bath(NE,2×10<sup>-5</sup> mol/L)of160 units when the slices were perfused with artificial cerebrospinal fluid （ACSF）.Most of theseresponses could be antagonized by Yohimbine(YOH,2×10<sup>-5</sup>～4×10<sup>-5</sup> mol/L).Nevertheless,when the perfusion fluid was changed,i.e.,with low Ca<sup>2+</sup>-high Mg<sup>2+</sup> ACSF（CM-ACSF）whichcould block the chemical synaptic transmission,26 out of 35 units were inhibited by NE and only1 unit excited.The inhibition could he blocked by YOH. A very significant difference（P【0.01）was seen between the data obtained in ACSF and those in CM-ACSF.Furthermore,all NE-inhibited units in ACSF were also NE-inhibited in CM-ACSF,but the majority of NE-excited u-nits in ACSF changed into NE-inhibited or NE-unresponsive in CM-ACSF.The results suggestedthat NE produced a direct inhibitory effect on neurons in DMN which was mediated by the post-synaptic alpha 2 adrenergic receptors.展开更多
Aging is a slow and progressive natural process that compromises the normal functions of cells,tissues,organs,and systems.The aging of the hypothalamic median eminence(ME),a structural gate linking neural and endocrin...Aging is a slow and progressive natural process that compromises the normal functions of cells,tissues,organs,and systems.The aging of the hypothalamic median eminence(ME),a structural gate linking neural and endocrine systems,may impair hormone release,energy homeostasis,and central sensing of circulating molecules,leading to systemic and reproductive aging.However,the molecular and cellular features of ME aging remain largely unknown.Here,we describe the transcriptional landscape of young and middleaged mouse ME at single-cell resolution,revealing the common and cell type-specific transcriptional changes with age.The transcriptional changes in cell-intrinsic programs,cell-cell crosstalk,and cellextrinsic factors highlight five molecular features of ME aging and also implicate several potentially druggable targets at cellular,signaling,and molecular levels.Importantly,our results suggest that vascular and leptomeningeal cells may lead the asynchronized aging process among diverse cell types and drive local inflammation and cellular senescence via a unique secretome.Together,our study uncovers how intrinsic and extrinsic features of each cell type in the hypothalamic ME are changed by the aging process,which will facilitate our understanding of brain aging and provide clues for efficient anti-aging intervention at the middle-aged stage.展开更多
Objective: To determine whether NMDA receptor activation mediates the expression of c--fos and NOS and study the relationship between the expression of c--fos and NOS in the hypothalamic paraventricularnucleus (PVN) f...Objective: To determine whether NMDA receptor activation mediates the expression of c--fos and NOS and study the relationship between the expression of c--fos and NOS in the hypothalamic paraventricularnucleus (PVN) following acute hypothermia and hypoxia. Methods: Fos immunohistochemistry, NADPH--d histochemistry and Fos/NADH--d double labeling were used. Results: Acute hypothermia and hypoxia induced the overexpression of on fos and NOS in PVN in rats. Pretreatment with ketamine, a NMDA receptor antagonist, resulted in partial inhibition of the expression of c--fos and NOS and that with blocker of NOS resulted in significant inhibition of the expression of c--fos. Conclusion: The activation of NMDA receptor is involved in the expression of c- fos and NOS in PVN in the rats subjected to acute hypothermia and hypoxia.Meanwhile, hypothalamic endogenous NO participates in adaptive reaction to hypothermia and hypoxia,which might be related to the modulation of c- fos expression.展开更多
基金supported by the Chief Scientist of Qi-Huang Project of the National Traditional Chinese Medicine Inheritance and Innovation“One Hundred Million”Talent Project,China(Grant No.:[2021]No.7)the National Famous Old Traditional Chinese Medicine Experts Inheritance Studio Construction Program of National Administration of Traditional Chinese Medicine,China(Grant No.:[2022]No.75)+3 种基金the Seventh Batch of National Famous Old Traditional Chinese Medicine Experts Experience Heritage Construction Program of National Administration of Traditional Chinese Medicine,China(Grant No.:[2022]No.76)Heilongjiang Touyan Innovation Team Program,China(Grant No.:[2019]No.5)the Natural Science Foundation of Zhejiang Province(Grant No.:LQN25H280009)the Research Project of Zhejiang Chinese Medical University,China(Grant No.:2023RCZXZK22).
文摘That herbs with the"hot"property used to treat"cold"syndromes is a guiding principle of clinical prescription and medication in traditional Chinese medicine(TCM).However,this theory of TCM is still in the‘black box'stage,and few in-depth studies have examined the biological mechanisms underpinning the hot properties of herbs.
基金Supported by the Excellent Youth Project of Anhui Universities,No.2022AH030065National Natural Science Foundation of China,No.82474224 and No.82405244+3 种基金Anhui Provincial Natural Science Foundation,No.2408085MH223Open Projects of Anhui Province Key Laboratory of Meridian Viscera Correlationship,No.2024AHMVC04Research Project of Xin’an Medical and Chinese Medicine Modernization Research Institute,No.2023CXMMTCM016the Anhui Province Scientific Research Planning Project,No.2022AH050438.
文摘BACKGROUND Visceral hypersensitivity is the core pathogenesis of irritable bowel syndrome(IBS)and is often accompanied by negative emotions such as anxiety or depression.Paraventricular hypothalamic nucleus(PVN)corticotropin-releasing factor(CRF)is involved in the stress-related gastrointestinal dysfunction.Electroacupuncture(EA)has unique advantages for the treatment of visceral hypersensitivity and negative emotions in IBS patients.However,the underlying mechanisms remain unclear.AIM To investigate the pathological mechanisms visceral hypersensitivity and negative emotions in IBS,as well as the effect mechanism of EA.METHODS A model of diarrhoeal IBS(IBS-D)with negative emotions was prepared by chronic restraint combined with glacial acetic acid enema.The effect of EA was verified by abdominal withdrawal reflex and open-field test.PVN CRFcolonic mast cell(MC)/transient potential receptor vanilloid type 1(TRPV1)pathway was detected by immunofluorescence,Western blot,ELISA,and toluidine blue staining.Moreover,PVN CRFergic neurons were activated or inhibited by chemogenetical technique to observe the changes of effect indicator.RESULTS In the model group,IBS-D symptoms and negative emotions were successfully induced.Notably,the combination of Baihui(GV20)with Tianshu(ST25)and Dachangshu(BL25)acupoints showed the greatest efficacy in improving the negative emotions and visceral hypersensitivity in model mice.Furthermore,we found that EA inhibited overactivated PVN CRFergic neurons and the overexpression of serum CRF,colonic CRF,CRF-receptor 1(CRFR1),mast cell tryptase(MCT),protease-activated receptor 2 and TRPV1 in model mice.Moreover,we found that activating PVN CRFergic neurons induced negative emotions and visceral hypersensitivity in normal mice;however,inhibiting PVN CRFergic neurons alleviated negative emotions and intestinal symptoms in model mice and decreased the expression of colonic CRF-R1,MCT,and TRPV1.CONCLUSION This research highlights the key role of PVN CRF-MC CRF-R1 and the downstream MC/TRPV1 pathway in the pathological process of IBS-D and the mechanism of the effect of EA.
基金Supported by the Natural Science Foundation of China,No.82070856the Science and Technology Development Plan of Shandong Medical and Health Science,No.202102040075+1 种基金Scientific Research Plan of Weifang Health Commission,No.WFWSJK-2022-010 and No.WFWSJK-2022-008Weifang Science and Technology Development Plan,No.2021YX071 and No.2021YX070.
文摘BACKGROUND Type 2 diabetes mellitus(T2DM)is often accompanied by impaired glucose utilization in the brain,leading to oxidative stress,neuronal cell injury and inflammation.Previous studies have shown that duodenal jejunal bypass(DJB)surgery significantly improves brain glucose metabolism in T2DM rats,the role and the metabolism of DJB in improving brain oxidative stress and inflammation condition in T2DM rats remain unclear.AIM To investigate the role and metabolism of DJB in improving hypothalamic oxidative stress and inflammation condition in T2DM rats.METHODS A T2DM rat model was induced via a high-glucose and high-fat diet,combined with a low-dose streptozotocin injection.T2DM rats were divided into DJB operation and Sham operation groups.DJB surgical intervention was carried out on T2DM rats.The differential expression of hypothalamic proteins was analyzed using quantitative proteomics analysis.Proteins related to oxidative stress,inflammation,and neuronal injury in the hypothalamus of T2DM rats were analyzed by flow cytometry,quantitative real-time PCR,Western blotting,and immunofluorescence.RESULTS Quantitative proteomics analysis showed significant differences in proteins related to oxidative stress,inflammation,and neuronal injury in the hypothalamus of rats with T2DM-DJB after DJB surgery,compared to the T2DM-Sham groups of rats.Oxidative stress-related proteins(glucagon-like peptide 1 receptor,Nrf2,and HO-1)were significantly increased(P<0.05)in the hypothalamus of rats with T2DM after DJB surgery.DJB surgery significantly reduced(P<0.05)hypothalamic inflammation in T2DM rats by inhibiting the activation of NF-κB and decreasing the expression of interleukin(IL)-1βand IL-6.DJB surgery significantly reduced(P<0.05)the expression of factors related to neuronal injury(glial fibrillary acidic protein and Caspase-3)in the hypothalamus of T2DM rats and upregulated(P<0.05)the expression of neuroprotective factors(C-fos,Ki67,Bcl-2,and BDNF),thereby reducing hypothalamic injury in T2DM rats.CONCLUSION DJB surgery improve oxidative stress and inflammation in the hypothalamus of T2DM rats and reduce neuronal cell injury by activating the glucagon-like peptide 1 receptor-mediated Nrf2/HO-1 signaling pathway.
基金supported by grants from the National Natural Science Foundation of China(No.82174496,No.82374574)Shanghai Key Discipline of Traditional Chinese Medicine Construction Project(No.shzyyzdxk–2024113)。
文摘Objective:This study investigates the sleep-modulating effects of ginsenoside Rg1(Rg1,C_(42)H_(72)O_(14)),a key bioactive component of ginseng,and elucidates its underlying mechanisms.Methods:C57BL/6J mice were intraperitoneally administered doses of Rg1 ranging from 12.5 to100 mg/kg.Sleep parameters were assessed to determine the average duration of each sleep stage by monitoring the electrical activity of the brain and muscles.Further,orexin neurons in the lateral hypothalamus(LH)and corticotropin-releasing hormone(CRH)neurons in the paraventricular hypothalamic nucleus(PVH)were ablated using viral vector surgery and electrode embedding.The excitability of LH^(orexin)and PVH^(CRH)neurons was evaluated through the measurement of cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog(c-Fos)expression.Results:Rg1(12.5–100 mg/kg)augmented the duration of non-rapid eye movement(NREM)sleep phases,while reducing the duration of wakefulness,in a dose dependent manner.The reduced latency from wakefulness to NREM sleep indicates an accelerated sleep initiation time.We found that these sleep-promoting effects were weakened in the LH^(orexin)and PVH^(CRH)neuron ablation groups,and disappeared in the orexin and CRH double-ablation group.Decreased c-Fos protein expression in the LH and PVH confirmed that Rg1 promoted NREM sleep by inhibiting orexin and CRH neurons.Conclusion:Rg1 increases the duration of NREM sleep,underscoring the essential roles of LH^(orexin)and PVH^(CRH)neurons in facilitating the sleep-promoting effects of Rg1.Please cite this article as:Wang YY,Wu Y,Yu KW,Xie HY,Gui Y,Chen CR,Wang NH.Ginsenoside Rg1 promotes non-rapid eye movement sleep via inhibition of orexin neurons of the lateral hypothalamus and corticotropin-releasing hormone neurons of the paraventricular hypothalamic nucleus.J Integr Med.2024;22(6):719–728.
文摘Objective To study the central role of ginkgolide B （BN52021） in regulating cardiovascular function of nerve center by examining the effects of ginkgolide B on the electrical activity of rat paraventricular nucleus （PVN） neurons in hypothalamic slice preparation and to elucidate the mechanism involved. Methods Extracellular single-unit discharge recording technique. Results （1） In response to the application of ginkgolide t3 （0.1, 1, 10 μmol/L; n = 27） into the perfusate for 2 rain, the spontaneous discharge rates （SDR） of 26 （26/27, 96.30%） neurons were significantly decreased in a dose-dependent manner. （2） Pretreatment with L-glutamate （L-Glu, 0.2 mmol/L） led to a marked increase in the SDR of all 8 （100%） neurons in an epileptiform pattern. The increased discharges were suppressed significantly after ginkgolide B （1 μmol/L） was applied into the perfusate for 2 min. （3） In 8 neurons, perfusion of the selective L-type calcium channel agonist, Bay K 8644 （0.1 μmol/L）, induced a significant increase in the discharge rates of 8 （8/8, 100%） neurons, while ginkgolide B （1μmol/L） applied into the perfusate, could inhibit the discharges of 8 （100%） neurons. （4） In 8 neurons, the broad potassium channels blocker, tetraethylammonium （TEA, 1 mmol/L） completely blocked the inhibitory effect of ginkgolide B （1 μmol/L）. Conclusion These results suggest that ginkgolide B can inhibit the electrical activity of paraventricular neurons. The inhibitory effect may be related to the blockade of L-type voltage-activated calcium channel and potentially concerned with delayed rectifier potassium channel （KDR）.
基金the National Natural Science Foundation of China(81571351,81620108012,81671373,and 81771427)a Discipline Promotion Project of Xijing Hospital(XJZT18MJ33).
文摘The lateral hypothalamic area(LHA)plays a pivotal role in regulating consciousness transition,in which orexinergic neurons,GABAergic neurons,and melanin-concentrating hormone neurons are involved.Glutamatergic neurons have a large population in the LHA,but their anesthesia-related effect has not been explored.Here,we found that genetic ablation of LHA glutamatergic neurons shortened the induction time and prolonged the recovery time of isoflurane anesthesia in mice.In contrast,chemogenetic activation of LHA glutamatergic neurons increased the time to anesthesia and decreased the time to recovery.Optogenetic activation of LHA glutamatergic neurons during the maintenance of anesthesia reduced the burst suppression pattern of the electroencephalogram(EEG)and shifted EEG features to an arousal pattern.Photostimulation of LHA glutamatergic projections to the lateral habenula(LHb)also facilitated the emergence from anesthesia and the transition of anesthesia depth to a lighter level.Collectively,LHA glutamatergic neurons and their projections to the LHb regulate anesthetic potency and EEG features.
基金grants from the National Natural Science Foundation of China, No. 30370533, 30570671the Educational Department Science Research Foundation of Jiangsu Province, No. 99KJB310005,05KJB310134
文摘AIM： To investigate the effects of electrical stimulation of hypothalamic paraventricular nuclei （PVN） on gastric mucosal cellular apoptosis and proliferation induced by gastric ischemia/reperfusion （I/R） injury. METHODS： For different experimental purposes, stimulating electrode plantation or electrolytic destruction of the PVN was applied, then the animals＇ GI/R injury model was established by clamping the celiac artery for 30 min and allowing reperfusing the artery for 30 rain, 1 h, 3 h or 6 h respectively. Then histological, immunohistochemistry methods were used to assess the gastric mucosal damage index, the gastric mucosal cellular apoptosis and proliferation at different times. RESULTS： The electrical stimulation of PVN significantly attenuated the GI/R injury at 30 min, i h and 3 h after reperfusion. The electrical stimulation of PVN decreased gastric mucosal apoptosis and increased gastric mucosal proliferation. The electrolytic destruction of the PVN could eliminate the protective effects of electrical stimulation of PVN on GI/R injury. These results indicated that the PVN participated in the regulation of GI/R injury as a specific area in the brain, exerting protective effects against the GI/R injury, and the protection was associated with the inhibition of cellular apoptosis and the promotion of gastric mucosal proliferation. CONCLUSION： Stimulating PVN significantly inhibits the gastric mucosal cellular apoptosis and promots gastric mucosal cellular proliferation. This may explain the protective mechanisms of electrical stimulation of PVN against GI/R injury.
基金Supported by National Natural Science Foundation of China:Mechanism of GABA/Glu Neural Circuit in Lateral HypothalamusParietal Nucleus in Alleviating Myocardial Ischemia-Reperfusion Injury by Acupuncture Preconditioning(82074536)Study on the Protective Effect of Acupuncture Pretreatment on Myocardial Ischemia-Reperfusion Injury Based on Hypothalamic-Cerebellar Neural Circuit(81774414)+2 种基金Mechanism of GABA Neural Circuit in the Paraventricular Nucleus of Hypothalamus and Ventrolateral Region of Medulla Oblongata in Alleviating Myocardial Ischemia-Reperfusion Injury Induced by Acupuncture Pretreatment(82104999)Natural Science Foundation of Anhui Province the Central Regulatory Mechanism of Acupuncture Regulating Cardiac Function(2108085Y30)Anhui Province University Outstanding Top Talent Cultivation Funding Project(gxgwfx2019025)
文摘OBJECTIVE:To explore whether the paraventricular nucleus(PVN)participates in regulation of the antimyocardial ischemia-reperfusion injury(MIRI)effect of electroacupuncture(EA)and whether this is achieved through the PVN-interposed nucleus(IN)neural pathway.METHODS:The modeling method of myocardial ischemia reperfusion injury was achieved by ligating the left anterior descending coronary artery in SpragueDawley rats.We used the Powerlab multi-channel physiological recorder system to record electrocardiograms and analyze the changes in ST segment displacement;2,3,5-Triphenyltetrazolium chloride staining was used to observe the percentage of myocardial infarction areas.Detecting cardiac troponin I(cTnI),lactate dehydrogenase(LDH)in serum was done with an enzyme-linked immunosorbent assay kit.Morphological changes in the myocardium were detected in each group with hematoxylin-eosin staining of paraffin sections.Detection of c-fos protein expression in the PVN of the hypothalamus was done with the immuneofluorescence method.The Plexon multi-channel acquisition system recorded PVN neuron discharges and local field potentials in each group of rats.Offline Sorter software was used for cluster analysis.Neuro Explorer software was used to perform autocorrelation,raster and frequency characteristics and spectral energy analysis of neuron signals in each group.RESULTS:Compared with the MIRI model group,the areas of myocardial infarction in the EA group were significantly reduced;the expression of cTnI,LDH in serum was decreased significantly.The firing frequency of pyramidal cells in the PVN was significantly increased and the spectrum energy map showed energy was reduced,c-fos expression in PVN was reduced,this indicated that neuronal activity in the PVN participates in the effect of EA improving myocardial injury.In addition,we used the kainic acid method to lesion the IN and observed that the effect of EA was weakened.For example,the area of myocardial infarction of lesion IN+EA group in rats was significantly increased compared with that resulting from EA group,the expression of cTnI,LDH in serum was significantly increased,the firing frequency of pyramidal cells in the PVN was significantly reduced.A spectral energy diagram shows that the energy after damage was higher than that of EA group.At the same time,the expression of c-fos in the PVN increased again.CONCLUSION:Our results indicated that the PVN-IN nerve pathway may participate as an effective pathway of EA to improve the effect of myocardial injury.
基金Supported by Grants from National Natural Science Foundation of China,No.81070305the Natural Science Foundation of Shandong Province,No.zr2010hm066
文摘AIM: To determine the expression levels of gastrointestinal nesfatin-1 in ventromedial hypothalamic nucleus (VMH)-lesioned (obese) and ventrolateral hypothalamic nucleus (VLH)-lesioned (lean) rats that exhibit an imbalance in their energy metabolism and gastric mobility.
基金the Scientific Foundation of the Ministry of Railway,No.6747600045
文摘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(JiangwanⅡ,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 2006.①Rats 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 5×10^(9) 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 0.5μg/0.5μL of KA in phosphate buffer(0.1 mol/L,pH 7.4),and the speed of infusion was 0.1μL per minute in order to perform KA-induced lesion of PVN.②Three 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:①The alteration of EEG and power spectrum of PVN during asthmatic attack in sensitized rats;②The 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.①Alteration 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[(18476.71±2140.94),(13838.75±2983.26)mV^(2),P<0.01],the percentage of theδpower andθpower decreased significantly(P<0.01),while the percentage ofαpower andβ1 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 ofδpower was decreased significantly(P<0.01),but theα,β1 andβ2 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.②The 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.
文摘Objective. To explore an effective method of surgical management of craniopharyngioma. Subjects and methods. Fifty patients with craniopharyngioma had total andsubtotal tumor ectomy. There were 29 males and 21 females, ranging in age from 15 to 56 years (mean 34.1 years). MR imaging showed that the tumors were locatedin the superior sellar region in 24 cases, in superior sella region and extended into the third ventricular floor in 19 cases, into parasella in 3 cases and down to intrasella in 4 cases. Complete cystic tumors were found in 5 cases, whilethe partial cystic tumor in 24 cases and complete solid tumors in 21 cases. Pterional approach was used in 48 patients and subfrontal approach in 2 patients. Great attention was paid to the preservation of the perforating arteries from thecarotid, posterior and anterior communicating and anterior choroidal arteries to the hypothalamic structures. The clinical outcome was evaluated according to the GOS scale.Results. Of the 50 patients surgically treated, 47 patients obtained total ectomy of the tumor and 3 patients with the secondary surgery had subtotal ectomy of the tumor. The pituitary stalk was preserved in 29(58%) patients, severed in 14 patients and unidentified in 7 patients. Forty-six patients regained a normal life; one patient needed assist in life. Of the 3 deaths, one patient died of diabetes insipidus, one of inhalation asphyxia, and another one of water and sodium disorders. Conclusion. Avoidance of the injury to the neural structures in the thirdventricular floor and preservation of the perforating arteries to hypothalamus are the key to achieve good surgical results in treating craniopharyngioma.
基金partially supported by a Grant-in-Aid for Scientific Research(C)(26462862)from the Japan Society for the Promotion of Science
文摘OBJECTIVES： An animal experiment clarified that insertion of an orthodontic apparatus activated the trigeminal neurons of the medulla oblongata. Orthodontic tooth movement is known to be associated with the sympathetic nervous system and controlled by the nucleus of the hypothalamus. However, the transmission of both has not been demonstrated in humans. The purpose of this study were to examine the activated cerebral areas using brain functional magnetic resonance imaging（MRI）, when orthodontic tooth separators were inserted, and to confirm the possibility of the transmission route from the medulla oblongata to the hypothalamus.METHODS： Two types of alternative orthodontic tooth separators（brass contact gauge and floss） were inserted into the right upper premolars of 10 healthy volunteers. Brain functional T2＊-weighted images and anatomical T1-weighted images were taken.RESULTS： The blood oxygenation level dependent（BOLD） signals following insertion of a brass contact gauge and floss significantly increased in the somatosensory association cortex and hypothalamic area.CONCLUSION： Our findings suggest the possibility of a transmission route from the medulla oblongata to the hypothalamus.
文摘Objective.. To compare the mechanisms of analgesia induced by four kinds of acupunture therapies at the trypothalamic level in adjuvant arthritic rats. Methods： Forty-eight SD rats were randomized into normal, model, electroacupuncture （EA）, filiform needle （FN）, pricking blood-letting （BL） and point injection （PI） groups, with 8 cases in each. EA （20-100 Hz, 2-4 V and duration of 20 min）, FN, BL PI were respectively applied to “Kunlun” （昆仑 BL 60）. Arthritis model was established by injecting complete Freund＇s adjuvant （0.1 mL） into the rat＇s right foot pad. Behavioral reactions, pain threshold （latancy of tail flick to heat stimulation） and local swelling severity （foot volurne） were detected; the cordents of β-endorphin （β-EP） and α- drenocortiootropin （ACTH） were assayed with radioimmunoassay; and the expression of pro-opi-omelanocortin （POMC） mRNA in hypot were determined with hybridization method. Results： The pain threshold was significantly enhanced by all the four kinds of acupuncture therapies, and the effects of EA and PI were more obvious （P〈0.05, P〈0.01）. The severity of local swelling was markedly alleviated by all the four kinds of acupuncture therapies （ P〈 0.01 ） without significant differences among them （P 〉 0.05）. The content of β-EP in the hypothalamus was obviously elevated by EA and FN （P〈 0.05, P 〈 0.01 ）, and the effect of EA was more obvious, but no marked effect of BL or PI on β-EP was found （ P 〉0.05）. The content of ACTH in hypothalamus was considerably elevated by PI （P〈0.05）, but not by the other three therapies. The expression of PCMCmRNA in hypothalamus was significantly strengthened by EA and FN （P〈0. 01）, but not by the other two therapies. Conclusion：EA, flliform needle, blood-letting and point-injection all can produce analgesic effect in adjuvant arthritis rats, the effect of EA and filiform needie may be related to their resultant increase of hypothalamic β-EP, and that of point-injectiON related to the increase of hypothalamic ACTH level.
文摘Hypothalamic Corticotropin-releasing factor (CRF) directly activates the hypothalamic pituitary adrenal axis (HPA axis) during the surgical trauma induced stress response. Electroacupuncture (EA) has been demonstrated to have stress relieving effects in breast surgery, colorectal surgery, prostatectomy and craniotomy. This study was aimed to investigate the hypothesis that EA could regulate hypothalamic CRF in surgical trauma rats. In experiment one, Sprague-Dawley (SD) male rats were divided into intact, model (10% partial hepatectomy), sham EA and EA group. Rats from the Sham EA and EA group were stimulated at ST36-Zusanli and SP6-Sanyiniiao acupoints twice, 24 hours before the surgery and immediately after the surgery. Expressions of hypothalamic CRF and CRFR, GABA receptors, glutamate decarboxylase (GAD), serum adrenocorticotropic hormone (ACTH) and Corticosterone (CORT) were observed at 2, 4, 8 and 24 h after the surgery by radioimmunoassay (RIA), western blot, real-time PCR and immunohistochemistry. In the experiment two, SD male rats were divided into the intact, model, model + vehicle, model + L-838,417 EA and EA + L838,417 group. It was found that hypothalamus CRF, serum ACTH and CORT levels were increased in model group compared with the intact group, and those in the EA group decreased in comparison with the model group. Compared with the model group, hypothalamus-aminobutyric acid (GABA) receptor Aα3 mRNA and protein expressions of the EA group raised strikingly. In conclusion, EA alleviated surgical stress response by improving the GABA synthesis in hypothalamus, thus enhancing GABA receptors’ inhibitory regulation of the HPA axis dysfunction in rats with acute surgical trauma.
文摘<div style="text-align:justify;"> <span style="font-family:Verdana;">The study of interactions between neuroendocrinology and immunology, or immunoendocrinology, is a recent field with the majority of its development in the last 30 years that involves communication between the nervous, endocrine, and immune systems. Homeostasis, development, aging, metabolism, infection, and inflammation are all influenced by the cross talk between these systems via hormones, cytokines, and neurotransmitters. The nervous system affects the immune system through either the hypothalamus-pituitary axes (adrenal, gonadal, thyroid, growth-hormone) neuropeptide and hormone signals or autonomic nervous system signals of norepinephrine and acetylcholine. On the other hand, the immune system passes feedback through cytokine type and concentration in the blood. Imbalance of any of these systems leads to increased risk in severity of metabolic, psychiatric, inflammatory or autoimmune diseases. These two systems are complex standalone and even more so in their interaction. Thus, the relationship between the immune system and the hypothalamus-pituitary-thyroid axis is necessary to be reviewed.</span> </div>
文摘The effects of somatostatin and cysteamine injected into theventromedial nucleus of hypothalamus(VMH)on somatostatin-likeimmunoreactivity(SLI)concentration in the gastric antral mucosa and portal veinplasma,as well as the gastric acid secretion were studied in anesthetized rats.TheSLI concentration in the gastric antral mucosa and portal vein plasma and thegastric acid output were significantly increased one hour after the injection ofsomatostatin(0.5μg/0.5μ1)into the VMH.Four hours later,the SLI concentrationin the mucosa was still higher than the control level,while the SLI level in theplasma and the acid secretion were close to those of controls.On the contrary,the SLI concentration in the mucosa and plasma and the acid output weremarkedly decreased at four hours after the injection of cysteamine(15μg/0.5μ1)into the VMH.The present results suggest that both exogenous and endogenoussomatostatin in the VMH have a facilitatory action on the gastric somatostatinconcentration and its release as well as on the gastric acid secretion,thus provid-ing evidence for hypothalamic control of gastric somatostatin and acid secretion.
文摘Extracellular discharges of neurons in the dorsomedial nucleus（DMN）were recordedwith glass microelectrode from rat hypothalamic slices.The firing frequency decreased in 77 andincreased in 48 units during the addition of norepinephrine into the bath(NE,2×10<sup>-5</sup> mol/L)of160 units when the slices were perfused with artificial cerebrospinal fluid （ACSF）.Most of theseresponses could be antagonized by Yohimbine(YOH,2×10<sup>-5</sup>～4×10<sup>-5</sup> mol/L).Nevertheless,when the perfusion fluid was changed,i.e.,with low Ca<sup>2+</sup>-high Mg<sup>2+</sup> ACSF（CM-ACSF）whichcould block the chemical synaptic transmission,26 out of 35 units were inhibited by NE and only1 unit excited.The inhibition could he blocked by YOH. A very significant difference（P【0.01）was seen between the data obtained in ACSF and those in CM-ACSF.Furthermore,all NE-inhibited units in ACSF were also NE-inhibited in CM-ACSF,but the majority of NE-excited u-nits in ACSF changed into NE-inhibited or NE-unresponsive in CM-ACSF.The results suggestedthat NE produced a direct inhibitory effect on neurons in DMN which was mediated by the post-synaptic alpha 2 adrenergic receptors.
基金supported by the National Key R&D Program of China(2019YFA0801900 and 2018YFA0801104)the National Natural Science Foundation of China(31771131,81891002,31921002,and 32070972)+3 种基金the Strategic Priority Research Program of Chinese Academy of Sciences(XDB32020000)the Hundred-Talent Program(Chinese Academy of Sciences)the Beijing Municipal Science&Technology Commission(Z210010 and Z181100001518001)the Baoding Technical Program(2141ZF027)。
文摘Aging is a slow and progressive natural process that compromises the normal functions of cells,tissues,organs,and systems.The aging of the hypothalamic median eminence(ME),a structural gate linking neural and endocrine systems,may impair hormone release,energy homeostasis,and central sensing of circulating molecules,leading to systemic and reproductive aging.However,the molecular and cellular features of ME aging remain largely unknown.Here,we describe the transcriptional landscape of young and middleaged mouse ME at single-cell resolution,revealing the common and cell type-specific transcriptional changes with age.The transcriptional changes in cell-intrinsic programs,cell-cell crosstalk,and cellextrinsic factors highlight five molecular features of ME aging and also implicate several potentially druggable targets at cellular,signaling,and molecular levels.Importantly,our results suggest that vascular and leptomeningeal cells may lead the asynchronized aging process among diverse cell types and drive local inflammation and cellular senescence via a unique secretome.Together,our study uncovers how intrinsic and extrinsic features of each cell type in the hypothalamic ME are changed by the aging process,which will facilitate our understanding of brain aging and provide clues for efficient anti-aging intervention at the middle-aged stage.
文摘Objective: To determine whether NMDA receptor activation mediates the expression of c--fos and NOS and study the relationship between the expression of c--fos and NOS in the hypothalamic paraventricularnucleus (PVN) following acute hypothermia and hypoxia. Methods: Fos immunohistochemistry, NADPH--d histochemistry and Fos/NADH--d double labeling were used. Results: Acute hypothermia and hypoxia induced the overexpression of on fos and NOS in PVN in rats. Pretreatment with ketamine, a NMDA receptor antagonist, resulted in partial inhibition of the expression of c--fos and NOS and that with blocker of NOS resulted in significant inhibition of the expression of c--fos. Conclusion: The activation of NMDA receptor is involved in the expression of c- fos and NOS in PVN in the rats subjected to acute hypothermia and hypoxia.Meanwhile, hypothalamic endogenous NO participates in adaptive reaction to hypothermia and hypoxia,which might be related to the modulation of c- fos expression.
