Release of Lipids Stored in the Intestine by Glucagon-Like Peptide-2 Involves a Gut-Brain Neural Pathway.

BACKGROUND: The gut hormone GLP-2 (glucagon-like peptide-2) plays important roles in lipid handling in the intestine. During postabsorptive stage, it releases preformed chylomicrons stored in the intestine, the underlying mechanisms of which are not well understood. Previous studies implicate the involvement of neural pathways in GLP-2's actions on lipid absorption in the intestine, but the role of such mechanisms in releasing postabsorptive lipid storage has not been established. METHODS: Here, in mesenteric lymph duct cannulated rats, we directly tested whether gut-brain neural communication mediates GLP-2's effects on postabsorptive lipid mobilization in the intestine. We performed total subdiaphragmatic vagotomy to disrupt the gut-brain neural communication and analyzed lipid output 5 hours after a lipid load in response to intraperitoneal GLP-2 or saline. RESULTS: Peripheral GLP-2 administration led to increased lymph lipid output and activation of proopiomelanocortin neurons in the arcuate nucleus of hypothalamus. Disruption of gut-brain neural communication via vagotomy blunted GLP-2's effects on promoting lipid release in the intestine. CONCLUSIONS: These results, for the first time, demonstrate a novel mechanism in which postabsorptive mobilization of intestinal lipid storage by GLP-2 enlists a gut-brain neural pathway.

Electroacupuncture alleviates myocardial ischemia-reperfusion injury by inhibiting hypothalamic paraventricular nucleus neurons projecting to the rostral ventrolateral medulla.

Accumulating evidence suggests that electroacupuncture (EA) has obvious therapeutic effects and unique advantages in alleviating myocardial ischemia-reperfusion injury (MIRI), while the underlying neuromolecular mechanisms of EA intervention for MIRI have not been fully elucidated. The aim of the study is to investigate the role of the neural pathway of hypothalamic paraventricular nucleus (PVN) neurons projecting to the rostral ventrolateral medulla (RVLM) in the alleviation of MIRI rats by EA preconditioning. MIRI models were established by ligating the left anterior descending coronary artery for 30 min followed by reperfusion for 2 h. Electrocardiogram recording, chemogenetics, enzyme-linked immunosorbent assay, multichannel physiology recording and haematoxylin-eosin and immunofluorescence staining methods were conducted to demonstrate that the firing frequencies of neurons in the PVN and the expression of c-Fos decreased by EA pretreatment. Meanwhile, EA preconditioning significantly reduced the levels of creatine kinase isoenzymes (CK-MB), cardiac troponin I (cTnI) and lactic dehydrogenase (LDH). Virus tracing showed a projection connection between PVN and RVLM. The inhibition of the PVN-RVLM neural pathway could replicate the protective effect of EA pretreatment on MIRI rats. However, the activation of the pathway weakened the effect of EA preconditioning. EA pretreatment alleviated MIRI by regulating PVN neurons projecting to RVLM. This work provides novel evidence of EA pretreatment for alleviating MIRI.

Helical Nanofiber Photoelectric Synaptic Devices for an Artificial Vision Nervous System.

Inspired by the helical structure and the resultant exquisite functions of biomolecules, helical polymers have received increasing attention. Here, a series of poly(3-hexylthiophene)-block-poly(phenyl isocyanide) (P3HT-b-PPI) copolymers were prepared using a simple one-pot living polymerization method. Interestingly, the P3HT80-b-PPI30 films were found to have a helical nanofiber structure. The corresponding device has superior optoelectronic properties, such as a broadened spectral response range from the visible band to the deep ultraviolet (DUV) and an approximately 5-fold longer carrier decay time after DUV light stimulation. An energy consumption of 1.44 fJ per synaptic event was obtained, which is the lowest energy consumption achieved so far with DUV light stimulation. The encryption and decryption of images are implemented using an array of devices. Finally, a photoreceptor neural pathway was constructed to achieve early warning for the recognition of the display of harmful light. This research provides an effective strategy for the development of a novel optoelectronic synaptic device.

Ascending Visual Pathways to the Telencephalon in Teleosts with Special Focus on Forebrain Visual Centers, Associated Neural Circuitries, and Evolution.

Visual pathways to the telencephalon in teleost fishes have been studied in detail only in a few species, and their evolutionary history remained unclear. On the basis of our recent studies we propose that there were two visual pathways in the common ancestor of teleosts, while one of them became lost in acanthopterygian fishes that emerged relatively recently. Our in-depth analyses on the connections of visual centers also revealed that there are connections shared with those of mammals, and retinotopic organization of the ascending connections is maintained at least to the level of the diencephalon in the yellowfin goby. The major visual telencephalic center, or the lateral part of the dorsal telencephalon (Dl), shows considerable species differences in the number of regions and cytoarchitecture. In particular, four highly specialized compartments are noted in the Dl of gobies, and we analyzed about 100 species of teleosts to investigate the evolution of the compartments in the Dl, which indicated that four compartments emerged only in Gobiiformes, while there are fewer specialized compartments in some other percomorph lineages. We also discuss the connections of forebrain visual centers with the cerebellum and other lower brain centers and infer possible functions of the circuitries.

Study of the influence of NGF-ß gene overexpression in human mesenchymal stem cells on the expression level of SOX1 and neural pathway genes.

BACKGROUND: Nerve growth factor (NGF) is a protein exhibiting an influence on the neural development and also, its' impact on the stem cells remains a great potential treatment strategy. The influence of its overexpression on the neural pathway differentiation on Wharton's Jelly derived MSC (WJ-MSC) has not been studied so far, but considering the fact that these cells are relatively easy to obtain, using them may indicate an innovative change in stem cell therapies. The aim of this study was to evaluate the effect of NGF overexpression in human mesenchymal stem cells (MSC) on SOX1 and genes related to the neural pathway. METHODS AND RESULTS: The lentiviral transduction was performed in order to obtain the NGF overexpression, as well as RT-PCR to evaluate the expression level SOX1, SOX2, NES, NGF under influence of overexpressed NGF protein in WJ-MSC. During the study we have observed a decrease in SOX1 expression as the marker of neural stem cells. Other than that an increase of SOX2, NES and NGF was noticed, as they all are markers of early-neural as well as already differentiated neural cells. The results show a great potential of using those examined genes' expression as a form of a new stem cell therapy. CONCLUSIONS: The achieved overexpression of NGF in this study, led the modified MSC onto the neural pathway as well as caused a decrease of SOX1 expression and an increase of expression of genes related to neural differentiated cells.

Neurotoxicity of nanoparticles entering the brain via sensory nerve-to-brain pathways: injuries and mechanisms.

Nanoparticles induce neurotoxicity following inhalation, oral administration, intravenous administration, or injection. Different pathways have various corresponding characteristics. Among them, the sensory nerve-to-brain pathways, which are direct neural pathways, bypass barriers such as the blood-brain barrier, which prevents the entry of the majority of nanoparticles into the brain. Subsequently, nanoparticles exert effects on sensory neuroreceptors and sensory nerves, causing central neurotoxicity. However, no studies have summarized sensory nerve-to-brain pathways for transporting nanoparticles. Here, we review recent findings on the potential sensory nerve pathways that promote nanoparticle entry into the brain, the effects of NPs on sensory receptors and sensory nerves, the central neurotoxicity induced by nanoparticles via sensory nerve pathways, and the possible mechanisms underlying these effects. In addition, the limitations of current research and possible trends for future research are also discussed. In summary, we hope that this review will serve as a reference, inspire ideas for further research into the neurotoxicity of nanoparticles, and facilitate the development of protective measures and treatment schemes for nanoparticle-induced neurotoxicity.

DTI study on rehabilitation of the congenital deafness auditory pathway and speech center by cochlear implantation.

PURPOSE: To explore the correlation between hearing and speech recovery levels after cochlear implantation and examined the preoperative microstructure of auditory pathways and speech centre using DTI. METHODS: (1) Fifty-two SNHL children between 0 and 6 years and 19 age and gender matched normal hearing subjects had received 3.0 T-MRI examination of the brain.FA, axial diffusion coefficient (λ‖), radial diffusion coefficient (λ⊥), and MD values in the lateral lemniscus, inferior colliculus, medial geniculate bodies, auditory radiations, Brodmann areas 41, 42, 22, 44, 45, and 39 were all measured bilaterally. (2) CAP and SIR scores were assessed in fourty-six cochlear implantation children at 6 months post-implant. Correlations among deaf children ages, FA value of bilateral inferior colliculus FA values, BA22, BA44, and postoperative CAP, and SIR scores were analyzed using multiple linear regression. RESULTS: The preoperative standard partial regression age coefficient of deaf children (|bi'| = 0.404) was slightly greater than that of the inferior colliculus (|bi'| = 0.377) FA value. CONCLUSION: Preoperative children ages and inferior colliculus FA values were important factors influencing postoperative CAP score. Inferior colliculus FA value is a vital influencing factor in rehabilitation after cochlear implantation.

Role of the serotonergic system in urethral continence reflexes during sneezing in rats.

To clarify the role of serotonin (5-HT) in the prevention of stress urinary incontinence (SUI) during sneezing, we investigated the effect of intraperitoneal application of p-chlorophenylalanine (PCPA; a serotonin synthesis inhibitor) and intravenous application of CP-809101 (a 5-HT2C agonist) or LP44 (a 5-HT7 agonist) using female rats, in which the neurally evoked continence reflex during sneezing was examined. Amplitudes of urethral pressure response during sneezing (A-URS), urethral baseline pressure (UBP) at the middle urethra, and sneeze-induced leak point pressure (S-LPP) were measured in normal female adult rats with or without drug administration. PCPA decreased A-URS by 35.1 cmH2O and UBP by 13.3 cmH2O compared with normal rats. In PCPA-administrated rats, CP-809101 increased A-URS by 24.1 cmH2O and UBP by 15.1 cmH2O, and LP44 also increased A-URS by 20.6 cmH2O and UBP by 11.4 cmH2O compared with rats treated with PCPA alone. SUI was observed with S-LPP of 40.1 cmH2O in PCPA-administrated rats, in which CP-809101 and LP44 increased S-LPP by 28.0 and 15.2 cmH2O, respectively, compared with rats treated with PCPA alone. The effects of CP-809101 and LP44 were antagonized by SB-242084 (a selective 5-HT2C antagonist) and SB-269970 (a selective 5-HT7 antagonist), respectively. These results indicate that activation of 5-HT receptors enhances the active urethral closure reflex during sneezing, at least in part via 5-HT2C and 5-HT7 receptors.

Lateral hypothalamic Orexin-A-ergic projections to the arcuate nucleus modulate gastric function in vivo.

It has been well-known that hypothalamic orexigenic neuropeptides, orexin-A, and melanin-concentrating hormone (MCH), play important roles in regulation of gastric function. However, what neural pathway mediated by the two neuropeptides affects the gastric function remains unknown. In this study, by way of nucleic stimulation and extracellular recording of single unit electrophysiological properties, we found that electrically stimulating the lateral hypothalamic area (LH) or microinjection of orexin-A into the arcuate nucleus (ARC) excited most gastric distension-responsive neurons in the nuclei and enhanced the gastric function including motility, emptying, and acid secretion of conscious rats. The results indicated that LH-ARC orexin-A-ergic projections may exist and the orexin-A in the ARC affected afferent and efferent signal transmission between ARC and stomach. As expected, combination of retrograde tracing and immunohistochemistry showed that some orexin-A-ergic neurons projected from the LH to the ARC. In addition, microinjection of MCH and its receptor antagonist PMC-3881-PI into the ARC affected the role of orexin-A in the ARC, indicating a possible involvement of the MCH pathway in the orexin-A role. Our findings suggest that there was an orexin-A-ergic pathway between LH and ARC which participated in transmitting information between the central nuclei and the gastrointestinal tract and in regulating the gastric function of rats.

GLP-2 regulation of intestinal lipid handling.

Lipid handling in the intestine is important for maintaining energy homeostasis and overall health. Mishandling of lipids in the intestine contributes to dyslipidemia and atherosclerotic cardiovascular diseases. Despite advances in this field over the past few decades, significant gaps remain. The gut hormone glucagon-like peptide-2 (GLP-2) has been shown to play pleotropic roles in the regulation of lipid handling in the intestine. Of note, GLP-2 exhibits unique actions on post-prandial lipid absorption and post-absorptive release of intestinally stored lipids. This review aims to summarize current knowledge in how GLP-2 regulates lipid processing in the intestine. Elucidating the mechanisms of GLP-2 regulation of intestinal lipid handling not only improves our understanding of GLP-2 biology, but also provides insights into how lipids are processed in the intestine, which offers opportunities for developing novel strategies towards prevention and treatment of dyslipidemia and atherosclerotic cardiovascular diseases.

Mapping the 5-HTergic neural pathways in perimenopausal mice and elucidating the role of oestrogen receptors in 5-HT neurotransmission.

Perimenopausal syndrome (PMS) encompasses neuropsychiatric symptoms, such as hot flashes and depression, which are associated with alterations in the 5-HTergic neural pathway in the brain. However, the specific changes and mechanisms underlying these alterations remain unclear. In this study, ovariectomized mice were used to successfully establish a perimenopause model, and the changes in the expression of 5-HT and its receptors (5-HT1AR and 5-HT2AR) across 72 brain regions in these ovariectomized mice were assessed by immunohistochemistry. Although both 5-HT and 5-HT1AR were widely expressed throughout the brain, only a limited number of regions expressed 5-HT2AR. Notably, decreased expression of 5-HT was observed across almost all brain regions in the ovariectomy (OVX) group compared with the Sham group. Altered expression of both receptors was found within areas related to hot flashes (the preoptic area) or mood disorders (the amygdala). Additionally, reduced oestrogen receptor (ER)α/ß expression was detected in cells in the raphe nucleus (RN), an area known to regulate body temperature. Results showed that ERα/ß positively regulate the transcriptional activity of the enzymes TPH2/MAOA, which are involved in serotonin metabolism during perimenopause. This study revealed the changes in 5-HT neuropathways (5-HT, 5-HT1AR and 5-HT2AR) in perimenopausal mice, mainly in brain regions related to regulation of the body temperature, mood, sleep and memory. This study clarified that the expression of oestrogen receptor decreased in perimenopause, which regulated the transcription levels of TPH2 and MAOA, and ultimately led to the reduction of 5-HT content, providing a new target for clinical diagnosis and treatment of perimenopausal diseases.

The role of the basal forebrain in general anesthesia.

The basal forebrain is a group of nerve nuclei on the ventral side of the ventral ganglion, composed of γ-aminobutyric acid neurons, glutamatergic neurons, cholinergic neurons, and orexigenic neurons. Previous studies have focused on the involvement of the basal forebrain in regulating reward, learning, movement, sleep-awakening, and other neurobiological behaviors, but its role in the regulation of general anesthesia has not been systematically elucidated. Therefore, the different neuronal subtypes in the basal forebrain and projection pathways in general anesthesia will be discussed in this paper. In this paper, we aim to determine and elaborate on the role of the basal forebrain in general anesthesia and the development of theoretical research and provide a new theory.

Dopamine D1-receptor-expressing pathway from the nucleus accumbens to ventral pallidum-mediated sevoflurane anesthesia in mice.

BACKGROUND: General anesthesia has long been used in clinical practice, but its precise pharmacological effects on neural circuits are not fully understood. Recent investigations suggest that the sleep-wake system may play a role in the reversible loss of consciousness induced by general anesthetics. Studies in mice have shown that microinjection of dopamine receptor 1 (D1R) agonists into the nucleus accumbens (NAc) promotes recovery from isoflurane anesthesia, while microinjection of D1R antagonists has the opposite effect. Furthermore, during the induction and maintenance of sevoflurane anesthesia, there is a significant decrease in extracellular dopamine levels in the NAc, which subsequently increases during the recovery period. These findings suggest the involvement of the NAc in the regulation of general anesthesia. However, the specific role of D1R-expressing neurons in the NAc during general anesthesia and the downstream effect pathways are still not well understood. METHODS: In order to analyze the impact of sevoflurane anesthesia on NAcD1R neurons and the NAcD1R -VP pathway, this study employed calcium fiber photometry to investigate alterations in the fluorescence intensity of calcium signals in dopamine D1-receptor-expressing neurons located in the nucleus accumbens (NAcD1R neurons) and the NAcD1R -VP pathway during sevoflurane anesthesia. Subsequently, optogenetic techniques were utilized to activate or inhibit NAcD1R neurons and their synaptic terminals in the ventral pallidum (VP), aiming to elucidate the role of NAcD1R neurons and the NAcD1R -VP pathway in sevoflurane anesthesia. These experiments were supplemented with electroencephalogram (EEG) recordings and behavioral tests. Lastly, a genetically-encoded fluorescent sensor was employed to observe changes in extracellular GABA neurotransmitters in the VP during sevoflurane anesthesia. RESULTS: Our findings revealed that sevoflurane administration led to the inhibition of NAcD1R neuron population activity, as well as their connections within the ventral pallidum (VP). We also observed a reversible reduction in extracellular GABA levels in the VP during both the induction and emergence phases of sevoflurane anesthesia. Additionally, the optogenetic activation of NAcD1R neurons and their synaptic terminals in the VP resulted in a promotion of wakefulness during sevoflurane anesthesia, accompanied by a decrease in EEG slow wave activity and burst suppression rate. Conversely, the optogenetic inhibition of the NAcD1R -VP pathway exerted opposite effects. CONCLUSION: The NAcD1R -VP pathway serves as a crucial downstream pathway of NAcD1R neurons, playing a significant role in regulating arousal during sevoflurane anesthesia. Importantly, this pathway appears to be associated with the release of GABA neurotransmitters from VP cells.

Dopamine D2-receptor neurons in nucleus accumbens regulate sevoflurane anesthesia in mice.

Introduction: The mechanism of general anesthesia remains elusive. In recent years, numerous investigations have indicated that its mode of action is closely associated with the sleep-wake pathway. As a result, this study aimed to explore the involvement of dopamine D2 receptor (D2R) expressing neurons located in the nucleus accumbens (NAc), a critical nucleus governing sleep-wake regulation, in sevoflurane anesthesia. Methods: This exploration was carried out using calcium fiber photometry and optogenetics technology, while utilizing cortical electroencephalogram (EEG), loss of righting reflex (LORR), and recovery of righting reflex (RORR) as experimental indicators. Results: The findings from calcium fiber photometry revealed a decrease in the activity of NAcD2R neurons during the induction phase of sevoflurane anesthesia, with subsequent recovery observed during the anesthesia's emergence phase. Moreover, the activation of NAcD2R neurons through optogenetics technology led to a reduction in the anesthesia induction process and an extension of the arousal process in mice. Conversely, the inhibition of these neurons resulted in the opposite effect. Furthermore, the activation of NAcD2R neurons projecting into the ventral pallidum (VP) via optogenetics demonstrated a shortened induction time for mice under sevoflurane anesthesia. Discussion: In conclusion, our research outcomes suggest that NAcD2R neurons play a promotive role in the sevoflurane general anesthesia process in mice, and their activation can reduce the induction time of anesthesia via the ventral pallidum (VP).

Effects of Pregabalin as a Neural Pathway Inhibitor for the Treatment of Resistant Subacute and Chronic Cough: A Pilot Clinical Trials Study.

BACKGROUND: Cough hypersensitivity syndrome is one of the causes of chronic cough. Small clinical trials have suggested the effects of pregabalin as a neural pathway inhibitor in treating subacute and chronic cough resistance. METHODS: This study is an 8-week, pilot study randomized, double-blind clinical trial on 30 patients' resistant to treatment of the underlying cause who were referred to an ultra-specialized lung clinic, Shahid Beheshti Hospital, between 2021-2022. The samples were randomly divided into control (dextromethorphan and placebo) and intervention (dextromethorphan and pregabalin). Patients were evaluated at the beginning, during, and after eight weeks of treatment, using the modified standard Leicester Cough Questionnaire (LCQ) regarding the changes and the rate of recovery compared to before Participation in the study. FINDINGS: The quality of life score of patients eight weeks after treatment had a significant difference and was higher in the intervention group (In the pregabalin group) than in the control group (p =0.006). The recovery rate of cough in 26% of patients was equal to 70%, but others were reported up to 50%. CONCLUSION: Pregabalin increases the quality of life in patients with subacute and chronic cough resistant to standard treatment and increases the rate of recovery in these patients.

Electrical nerve stimulation for sensory-neural pathway reconstruction in upper-limb amputees.

Introduction: The loss of the neural sensory function pathways between the stump limbs and the brain greatly impacts the rehabilitation of limb function and the daily lives of amputees. Non-invasive physical stressors, such as mechanical pressure and transcutaneous electrical nerve stimulation (TENS), could be potential solutions for recovering somatic sensations in amputees. Previous studies have shown that stimulating the residual or regenerated nerves in the stumps of some amputees can produce phantom hand sensations. However, the results are inconclusive due to unstable physiological responses caused by inaccurate stimulus parameters and positions. Methods: In this study, we developed an optimal TENS strategy by mapping the distribution of the nerves in the stump skin that elicitsphantom sensations known as a "phantom hand map." We evaluated the effectiveness and stability of the confirmed stimulus configuration in a long-term experiment using single- and multi-stimulus paradigms. Additionally, we evaluated the evoked sensations by recording electroencephalograms (EEG) and analyzing brain activities. Results: The results demonstrated that various types of intuitive sensations for amputees could be stably induced by adjusting TENS frequencies, particularly at 5 and 50 Hz. At these frequencies, 100% stability of sensory types was achieved when the stimuli were applied to two specific locations on the stump skin. Furthermore, at these locations, the stability of sensory positions was 100% across different days. Moreover, the evoked sensations were objectively supported by specific patterns of event-related potentials in brain responses. Discussion: This study provides an effective method for developing and evaluating physical stressor stimulus strategies, which could play an important role in the somatosensory rehabilitation of amputees and other patients suffering from somatomotor sensory dysfunction. The paradigm developed in this study can provide effective guidelines for stimulus parameters in physical and electrical nerve stimulation treatments for a variety of symptoms related to neurological disorders.

Neural control of cerebral blood flow: scientific basis of scalp acupuncture in treating brain diseases.

Scalp acupuncture (SA), as a modern acupuncture therapy in the treatment of brain diseases, especially for acute ischemic strokes, has accumulated a wealth of experience and tons of success cases, but the current hypothesized mechanisms of SA therapy still seem to lack significant scientific validity, which may not be conducive to its ultimate integration into mainstream medicine. This review explores a novel perspective about the mechanisms of SA in treating brain diseases based on its effects on cerebral blood flow (CBF). To date, abundant evidence has shown that CBF is significantly increased by stimulating specific SA points, areas or nerves innervating the scalp, which parallels the instant or long-term improvement of symptoms of brain diseases. Over time, the neural pathways that improve CBF by stimulating the trigeminal, the facial, and the cervical nerves have also been gradually revealed. In addition, the presence of the core SA points or areas frequently used for brain diseases can be rationally explained by the characteristics of nerve distribution, including nerve overlap or convergence in certain parts of the scalp. But such characteristics also suggest that the role of these SA points or areas is relatively specific and not due to a direct correspondence between the current hypothesized SA points, areas and the functional zones of the cerebral cortex. The above evidence chain indicates that the efficacy of SA in treating brain diseases, especially ischemic strokes, is mostly achieved by stimulating the scalp nerves, especially the trigeminal nerve to improve CBF. Of course, the mechanisms of SA in treating various brain diseases might be multifaceted. However, the authors believe that understanding the neural regulation of SA on CBF not only captures the main aspects of the mechanisms of SA therapy, but also facilitates the elucidation of other mechanisms, which may be of greater significance to further its clinical applications.

Magnetic Resonance Imaging in Diplopia: Neural Pathway, Imaging, and Clinical Correlation.

The role of magnetic resonance imaging (MRI) in diplopia is to diagnose various diseases that occur along the neural pathway governing eye movement. However, the lesions are frequently small and subtle and are therefore difficult to detect on MRI. This article presents representative cases of diseases that cause diplopia. The purpose of this article was to 1) describe the anatomy of the neural pathway governing eye movement, 2) recommend optimal MRI targets and protocols for the diagnosis of diseases causing diplopia, 3) correlate MRI findings with misalignment of the eyes (i.e., strabismus), and 4) help familiarize the reader with the imaging diagnosis of diplopia.

[Effects of Angelicae Sinensis Radix on cAMP/Epac signaling pathway in the treatment of chronically infected cough mice with Yin deficiency syndrome].

OBJECTIVE: To investigate the effects of Angelicae Sinensis Radix (ASR) on cyclic adenosine monophosphate (cAMP) /exchange protein activated by cAMP (Epac) signaling pathway in the treatment of chronically infected cough mice with Yin deficiency syndrome. METHODS: Mice were randomly divided into blank control group, model control group, positive control group and ASR group (n=8). The chronic cough mouse model of hyperreactive and infected airway with Yin deficiency syndrome was established with fumigation (once a day, 30 days in total), lipopolysaccharide nasal drip (every 3 days 10 µl, 10 times in total), intragastric administration of thyroid gland (120 mg/kg, once a day, a total of 15 days) and inhalation of ammonia (3 min / time × 10 times). On the basis of observing eating and drinking water, body weight and autonomic activities, the effects of ASR on metabolic level, autonomous activities, antitussive effect, cell factor in bronchoalveolar lavage fluid (BALF) brain tissue 5-HT and lung tissue related active factors(SP, PGP9.5, cAMP, Epac1) were detected. RESULTS: ASR could significantly restrain cough, alleviate the pathological changes of bronchioles, reduce the contents of IL-4, IL-13, TNF-α in BALF and the levels of SP, PGP9.5, cAMP and Epac1 in lung tissues, increase the content of 5-HT in brain tissue (P＜0.05, 0.01). CONCLUSION: ASR has some effects on restraining cough and one of its mechanisms is to down-regulate cAMP/Epac signaling pathway, to alleviate airway neurogenic inflammation and reduce sensitivity of cough neural pathway.

[Effects of ARC-hippocampus obestatin neural pathway on gastric motility and gastric emptying in diabetic rats].

Objective: To investigate the obestatin neural projections from arcuate nucleus (ARC) to hippocampus in diabetic rats, and its effects on gastric motility and gastric emptying of rats. Methods: Diabetic model was established by fructose intake combined with streptozotocin injected intraperitoneally in healthy male Wistar rats. Diabetic rats were randomly divided into five groups: control group (NS group), 0.1, 1 and 10 pmol obestatin group, and obestatin + NBI27914 group, with 7 rats in each group. 0.5 µl saline (NS), obestatin (0.1 pmol, 1 pmol, 10 pmol) or the mixture (10 pmol obestatin + 60 pmol NBI27914) was injected into the hippocampus respectively, the gastric motility was recorded immediately after administration, and the gastric emptying was studied 15 min later. ARC-hippocampus obestatin neural pathway and ARC obestatin mRNA expression were compared between normal and diabetic rats with fluorogold (FG) retrograde tracing and immunofluorescence histochemical staining. Results: Compared with normal rats, the number of ARC FG/obestatin double labeled neurons and the expression level of ARC obestatin mRNA were decreased significantly in diabetic rats (P＜0.05); Obestatin could inhibit gastric motility and gastric emptying in a dose-dependent manner (P＜0.05~0.01) and the effects of obestatin could be partially blocked by NBI27914, an antagonist of corticotropin releasing factor receptor 1 (CRFR1) (P＜0.05). Compared with normal rats, the inhibitory effects of obestatin on gastric motility and gastric emptying were significantly decreased in diabetic rats (P＜0.05). Conclusion: There is an obestatin neural pathway between ARC and hippocampus, which participates in the regulation of gastric motility and gastric emptying in diabetic rats, and CRFR1 signal pathway is involved in this process. The damage of this neural pathway may participate in gastric motility dysfunction in early stage of diabetes.