AIM: To study the neural mechanism by which electroacupuncture(EA) at RN12(Zhongwan) and BL21(Weishu) regulates gastric motility.METHODS: One hundred and forty-four adult Sprague Dawley rats were studied in four separ...AIM: To study the neural mechanism by which electroacupuncture(EA) at RN12(Zhongwan) and BL21(Weishu) regulates gastric motility.METHODS: One hundred and forty-four adult Sprague Dawley rats were studied in four separate experiments. Intragastric pressure was measured using custommade rubber balloons, and extracellular neuron firing activity, which is sensitive to gastric distention in the dorsal vagal complex(DVC), was recorded by an electrophysiological technique. The expression levels of c-fos, motilin(MTL) and gastrin(GAS) in the paraventricular hypothalamic nucleus(PVN) were assayed by immunohistochemistry, and the expression levels of motilin receptor(MTL-R) and gastrin receptor(GAS-R) in both the PVN and the gastric antrum were assayed by western blotting.RESULTS: EA at RN12 + BL21(gastric Shu and Mu points), BL21(gastric Back-Shu point), RN12(gastric Front-Mu point), resulted in increased neuron-activating frequency in the DVC(2.08 ± 0.050, 1.17 ± 0.023, 1.55 ± 0.079 vs 0.75 ± 0.046, P < 0.001) compared with a model group. The expression of c-fos(36.24 ± 1.67, 29.41 ± 2.55, 31.79 ± 3.00 vs 5.73 ± 2.18, P < 0.001), MTL(22.48 ± 2.66, 20.76 ± 2.41, 19.17 ± 1.71 vs 11.68 ± 2.52, P < 0.001), GAS(24.99 ± 2.95, 21.69 ± 3.24, 23.03 ± 3.09 vs 12.53 ± 2.15, P < 0.001), MTL-R(1.39 ± 0.05, 1.22 ± 0.05, 1.17 ± 0.12 vs 0.84 ± 0.06, P < 0.001), and GAS-R(1.07 ± 0.07, 0.91 ± 0.06, 0.78 ± 0.05 vs 0.45 ± 0.04, P < 0.001) increased in the PVN after EA compared with the model group. The expression of MTL-R(1.46 ± 0.14, 1.26 ± 0.11, 0.99 ± 0.07 vs 0.65 ± 0.03, P < 0.001), and GAS-R(1.63 ± 0.11, 1.26 ± 0.16, 1.13 ± 0.02 vs 0.80 ± 0.11, P < 0.001) increased in the gastric antrum after EA compared with the model group. Damaging the PVN resulted in reduced intragastric pressure(13.67 ± 3.72 vs 4.27 ± 1.48, P < 0.001). These data demonstrate that the signals induced by EA stimulation of acupoints RN12 and BL21 are detectable in the DVC and the PVN, and increase the levels of gastrointestinal hormones and their receptors in the PVN and gastric antrum to regulate gastric motility. CONCLUSION: EA at RN12 and BL21 regulates gastric motility, which may be achieved through the PVN-DVCvagus-gastric neural pathway.展开更多
Coronary heart disease (CHD) that is due to atherosclerosis is associated with low-grade systemic inflammation. Congestive cardiac failure and arrhythmias that are responsible for mortality in CHD can be suppressed by...Coronary heart disease (CHD) that is due to atherosclerosis is associated with low-grade systemic inflammation. Congestive cardiac failure and arrhythmias that are responsible for mortality in CHD can be suppressed by appropriate vagal stimulation that is anti-inflammatory in nature. Acetylcholine, the principal vagal neurotransmitter, is a potent anti-inflammatory molecule. Polyunsaturated fatty acids (PUFAs) augment acetylcholine release, while acetylcholine can enhance the formation of prostacyclin, lipoxins, resolvins, protectins and maresins from PUFAs, which are anti-inflammatory and anti-arrhythmic molecules. Furthermore, plasma and tissue levels of PUFAs are low in those with CHD and atherosclerosis. Hence, vagal nerve stimulation is beneficial in the prevention of CHD and cardiac arrhythmias. Thus, measurement of catecholamines, acetylcholine, various PUFAs, and their products lipoxins, resolvins, protectins and maresins in the plasma and peripheral leukocytes, and vagal tone by heart rate variation could be useful in the prediction, prevention and management of CHD and cardiac arrhythmias.展开更多
The adaptability of the central nervous system has been revealed in several model systems.Of particular interest to central nervous system-injured individuals is the ability for neural components to be modified for re...The adaptability of the central nervous system has been revealed in several model systems.Of particular interest to central nervous system-injured individuals is the ability for neural components to be modified for regain of function.In both types of neurotrauma,traumatic brain injury and spinal cord injury,the primary parasympathetic control to the gastrointestinal tract,the vagus nerve,remains anatomically intact.However,individuals with traumatic brain injury or spinal cord injury are highly susceptible to gastrointestinal dysfunctions.Such gastrointestinal dysfunctions attribute to higher morbidity and mortality following traumatic brain injury and spinal cord injury.While the vagal efferent output remains capable of eliciting motor responses following injury,evidence suggests impairment of the vagal afferents.Since sensory input drives motor output,this review will discuss the normal and altered anatomy and physiology of the gastrointestinal vagal afferents to better understand the contributions of vagal afferent plasticity following neurotrauma.展开更多
AIM: To conduct the first systematic test of the hypothesis that modulation of cardiac vagal tone is impaired in Lyme disease.METHODS: The response of cardiac vagal tone to respiratory modulation was measured in 18 se...AIM: To conduct the first systematic test of the hypothesis that modulation of cardiac vagal tone is impaired in Lyme disease.METHODS: The response of cardiac vagal tone to respiratory modulation was measured in 18 serologically positive Lyme disease patients and in 18 controls.RESULTS: The two groups were matched in respect of age,sex,body mass,mean arterial blood pressure,mean resting heart rate and mean resting cardiac vagal tone. The mean maximum cardiac vagal tone during deep breathing in the Lyme disease patients [11.2(standard error 1.3)] was lower than in the matched controls [16.5(standard error 1.7); P = 0.02].CONCLUSION: Respiratory modulation of cardiac vagal tone is impaired in Lyme disease,which suggests that Lyme disease may directly affect the vagus nerve or the brainstem.展开更多
Chronic experiments were made on eighteen dogs with Thomas pancreatic fistula andgastric fistula. Both in chronic and acute experiments the degenerated right cervical vagusnerve was stimulated by electrical shock and ...Chronic experiments were made on eighteen dogs with Thomas pancreatic fistula andgastric fistula. Both in chronic and acute experiments the degenerated right cervical vagusnerve was stimulated by electrical shock and the endogenous secretin and CCK was releasedby means of duodenal acidification (D. A.). The exogenous secretin, atropine and lidocainewere infused to analyse the interrelationship of neurohormones in the pancreatic exocrinesecretion. The results were as follows. In chronic experiments the pancreatic secretory la-tency was shorter and volume larger than that in acute experiments induced by D. A. Thedifference is very significant (P【0.001). Both vagotomy and atropine significantly inhibitedpancreatic secretion induced by D. A. (P【0.01). Lidocaine infused into duodenum inhibitedpancreatic secretion induced by D. A. as well. When vagal stimulation was combined withD. A., either simultaneously or successively, the pancreatic secretion was increased morethan the additive sum obtained by展开更多
Baroreflex plays a significant role in modulating blood pressure for the human body.It is known that activation of the vagal nerve related to baroreflex can lead to reductions of blood pressure.However,how the vagal a...Baroreflex plays a significant role in modulating blood pressure for the human body.It is known that activation of the vagal nerve related to baroreflex can lead to reductions of blood pressure.However,how the vagal activities quantitatively relate with blood pressure can hardly be achieved.Here fine carbon nanotube yarn(CNTy)electrodes were adopted for recording intrafascicular vagal activities,synchronized with measurement of arterial blood pressure in a rat.Together with a novel algorithm,the results preliminarily quantified that there were six clusters of neural spikes within recorded vagal activities,and the number of individual vagal spikes correspondingly varied with blood pressure.Especially for Cluster 2,the neural activations decreased with arterial blood pressure increasing.This study can shed lights on the quantified neural mechanism underlying the control of vagal activities on blood pressure,and guide the vagal-nerve neuromodulation for treating hypertension.展开更多
Extracellular pH (pHe) and intracellular pH (pHi) are important factors for the excitability of chemosensitive central respiratory neurons that play an important role in respiration and obstructive sleep apnea. It has...Extracellular pH (pHe) and intracellular pH (pHi) are important factors for the excitability of chemosensitive central respiratory neurons that play an important role in respiration and obstructive sleep apnea. It has been proposed that inhibition of central Na+/ H+exchanger 3 (NHE-3), a key pH i regulator in the brainstem, decreases the pH i, leading to membrane depolarization for the maintenance of respiration. However, how intracellular pH affects the neuronal excitability of respiratory neurons remains largely unknown. In this study, we showed that NHE-3 mRNA is widely distributed in respiration-related neurons of the rat brainstem, including the dorsal vagal nucleus (DVN). Whole-cell patch clamp recordings from DVN neurons in brain slices revealed that the standing outward current (Iso) through pH-sensitive K+channels was inhibited in the presence of the specific NHE-3 inhibitor AVE0657 that decreased the pH i. Exposure of DVN neurons to an acidified pH e and AVE0657 (5 μmol/L) resulted in a stronger effect on firing rate and I so than acidified pH e alone. Taken together, our results showed that intracellular acidification by blocking NHE-3 results in inhibition of a pHsensitive K+current, leading to synergistic excitation of chemosensitive DVN neurons for the regulation of respiration.展开更多
The glycemia-sensitive neuron in lateral hypothalamic area (LHA) is one of the important central neural events involved in the feeding control. Electrophysio-logical studies have demonstrated that gastrointestinal vag...The glycemia-sensitive neuron in lateral hypothalamic area (LHA) is one of the important central neural events involved in the feeding control. Electrophysio-logical studies have demonstrated that gastrointestinal vagal afferent inputs could convey the meal-related information of gastrointestinal tract to the hypothalamus. In this study, we examined whether the gastric vagal afferent inputs could reach the glycemia-sensitive neurons of the LHA by using in vivo extracellular recording technique in the rat. The results showed that stimulation of gastric vagal nerves elicited two types of the LHA neurons responses: the phasic response (93/116, 80.2%) and the change in cells firing pattern (23/116, 19.8%). Within the 93 cells that responded to the gastric vagal stimulation with a phasic response, 67 (72.0%) showed an inhibition in the cells firing rate, 26 (27.4%) were excited. Of the 23 cells that showed a change in the firing pattern, 13 responded to the gastric vagal stimulation with a long-lasting increase or decrease in firing rate, the remaining 10 cells turned their discrete spiking to the burst discharging. In addition, of 101 LHA neurons including the two types of responsive neurons, 73 (72.3%) were identified to be glyce-mia-sensitive neurons. These results demonstrated that the gastric vagal afferent inputs could reach the LHA and pre-dominantly reach those glycemia-sensitive neurons in the LHA. Presumably, the modulation of glycemia-sensitive neurons of LHA by the gastric vagal afferent inputs may play an important role in the short-term regulation of feed-ing behavior.展开更多
Recognizing the composition and modulation of the microbiome, a viable therapeutic tool for multi-targeted therapy is a new strategy that has recently been explored. Glucosamine (GS) is being studied for its prebiotic...Recognizing the composition and modulation of the microbiome, a viable therapeutic tool for multi-targeted therapy is a new strategy that has recently been explored. Glucosamine (GS) is being studied for its prebiotic potential in addition to being the most abundant and naturally occurring amino monosaccharide. The current study focuses on glucosamine’s prebiotic potential by assessing the stability of various GS concentrations (1% - 5%) in the gastrointestinal tract (GIT) and its ability to be fermented by the gut microbiota. The results showed that GS stimulated the most growth in L. acidophilus even after a longer incubation time than B. bifidum and L. acidophilus growth was concentration-dependent, with maximum growth at 3% with a simultaneous decrease in pH (5.6 - 1.7). The decrease in GS concentration with time also represented the growth of bacterial species, demonstrating the species’ utilization of GS. Furthermore, at 3%, GS also represented the prebiotic index of 1.9. In addition, the concentration of GS in various simulated GIT fluids was estimated in both fast and fed conditions to examine GS stability at various levels in the gut. The results showed that GS remained unaffected and non-digestible in all of the simulated GIT fluids (salivary, gastric, intestinal, and colonic), but there was a slight decrease in GS concentration (2.8%) in the fasted state of gastric fluid due to low pH levels (1.6). As a result, the findings are conclusive and suggest that GS possesses prebiotic properties.展开更多
基金Supported by The National Nature Science Foundation Council of ChinaNo.81473784+3 种基金the Natural Science Foundation of Anhui ProvinceNo.1408085MH166the Natural Science Foundation of Anhui University of Traditional Chinese MedicineNo.2013qn002
文摘AIM: To study the neural mechanism by which electroacupuncture(EA) at RN12(Zhongwan) and BL21(Weishu) regulates gastric motility.METHODS: One hundred and forty-four adult Sprague Dawley rats were studied in four separate experiments. Intragastric pressure was measured using custommade rubber balloons, and extracellular neuron firing activity, which is sensitive to gastric distention in the dorsal vagal complex(DVC), was recorded by an electrophysiological technique. The expression levels of c-fos, motilin(MTL) and gastrin(GAS) in the paraventricular hypothalamic nucleus(PVN) were assayed by immunohistochemistry, and the expression levels of motilin receptor(MTL-R) and gastrin receptor(GAS-R) in both the PVN and the gastric antrum were assayed by western blotting.RESULTS: EA at RN12 + BL21(gastric Shu and Mu points), BL21(gastric Back-Shu point), RN12(gastric Front-Mu point), resulted in increased neuron-activating frequency in the DVC(2.08 ± 0.050, 1.17 ± 0.023, 1.55 ± 0.079 vs 0.75 ± 0.046, P < 0.001) compared with a model group. The expression of c-fos(36.24 ± 1.67, 29.41 ± 2.55, 31.79 ± 3.00 vs 5.73 ± 2.18, P < 0.001), MTL(22.48 ± 2.66, 20.76 ± 2.41, 19.17 ± 1.71 vs 11.68 ± 2.52, P < 0.001), GAS(24.99 ± 2.95, 21.69 ± 3.24, 23.03 ± 3.09 vs 12.53 ± 2.15, P < 0.001), MTL-R(1.39 ± 0.05, 1.22 ± 0.05, 1.17 ± 0.12 vs 0.84 ± 0.06, P < 0.001), and GAS-R(1.07 ± 0.07, 0.91 ± 0.06, 0.78 ± 0.05 vs 0.45 ± 0.04, P < 0.001) increased in the PVN after EA compared with the model group. The expression of MTL-R(1.46 ± 0.14, 1.26 ± 0.11, 0.99 ± 0.07 vs 0.65 ± 0.03, P < 0.001), and GAS-R(1.63 ± 0.11, 1.26 ± 0.16, 1.13 ± 0.02 vs 0.80 ± 0.11, P < 0.001) increased in the gastric antrum after EA compared with the model group. Damaging the PVN resulted in reduced intragastric pressure(13.67 ± 3.72 vs 4.27 ± 1.48, P < 0.001). These data demonstrate that the signals induced by EA stimulation of acupoints RN12 and BL21 are detectable in the DVC and the PVN, and increase the levels of gastrointestinal hormones and their receptors in the PVN and gastric antrum to regulate gastric motility. CONCLUSION: EA at RN12 and BL21 regulates gastric motility, which may be achieved through the PVN-DVCvagus-gastric neural pathway.
文摘Coronary heart disease (CHD) that is due to atherosclerosis is associated with low-grade systemic inflammation. Congestive cardiac failure and arrhythmias that are responsible for mortality in CHD can be suppressed by appropriate vagal stimulation that is anti-inflammatory in nature. Acetylcholine, the principal vagal neurotransmitter, is a potent anti-inflammatory molecule. Polyunsaturated fatty acids (PUFAs) augment acetylcholine release, while acetylcholine can enhance the formation of prostacyclin, lipoxins, resolvins, protectins and maresins from PUFAs, which are anti-inflammatory and anti-arrhythmic molecules. Furthermore, plasma and tissue levels of PUFAs are low in those with CHD and atherosclerosis. Hence, vagal nerve stimulation is beneficial in the prevention of CHD and cardiac arrhythmias. Thus, measurement of catecholamines, acetylcholine, various PUFAs, and their products lipoxins, resolvins, protectins and maresins in the plasma and peripheral leukocytes, and vagal tone by heart rate variation could be useful in the prediction, prevention and management of CHD and cardiac arrhythmias.
基金the National Institutes of Health(NINDS 49177NINDS 105987)+1 种基金Craig H.Neilsen Foundation Senior Research award(295319)to GMHa grant from the National Institutes of Health(NINDS F31 NS 087834)to EMB。
文摘The adaptability of the central nervous system has been revealed in several model systems.Of particular interest to central nervous system-injured individuals is the ability for neural components to be modified for regain of function.In both types of neurotrauma,traumatic brain injury and spinal cord injury,the primary parasympathetic control to the gastrointestinal tract,the vagus nerve,remains anatomically intact.However,individuals with traumatic brain injury or spinal cord injury are highly susceptible to gastrointestinal dysfunctions.Such gastrointestinal dysfunctions attribute to higher morbidity and mortality following traumatic brain injury and spinal cord injury.While the vagal efferent output remains capable of eliciting motor responses following injury,evidence suggests impairment of the vagal afferents.Since sensory input drives motor output,this review will discuss the normal and altered anatomy and physiology of the gastrointestinal vagal afferents to better understand the contributions of vagal afferent plasticity following neurotrauma.
文摘AIM: To conduct the first systematic test of the hypothesis that modulation of cardiac vagal tone is impaired in Lyme disease.METHODS: The response of cardiac vagal tone to respiratory modulation was measured in 18 serologically positive Lyme disease patients and in 18 controls.RESULTS: The two groups were matched in respect of age,sex,body mass,mean arterial blood pressure,mean resting heart rate and mean resting cardiac vagal tone. The mean maximum cardiac vagal tone during deep breathing in the Lyme disease patients [11.2(standard error 1.3)] was lower than in the matched controls [16.5(standard error 1.7); P = 0.02].CONCLUSION: Respiratory modulation of cardiac vagal tone is impaired in Lyme disease,which suggests that Lyme disease may directly affect the vagus nerve or the brainstem.
基金Study supported by the Chinese Academy of Sciences Grant (84) 246.
文摘Chronic experiments were made on eighteen dogs with Thomas pancreatic fistula andgastric fistula. Both in chronic and acute experiments the degenerated right cervical vagusnerve was stimulated by electrical shock and the endogenous secretin and CCK was releasedby means of duodenal acidification (D. A.). The exogenous secretin, atropine and lidocainewere infused to analyse the interrelationship of neurohormones in the pancreatic exocrinesecretion. The results were as follows. In chronic experiments the pancreatic secretory la-tency was shorter and volume larger than that in acute experiments induced by D. A. Thedifference is very significant (P【0.001). Both vagotomy and atropine significantly inhibitedpancreatic secretion induced by D. A. (P【0.01). Lidocaine infused into duodenum inhibitedpancreatic secretion induced by D. A. as well. When vagal stimulation was combined withD. A., either simultaneously or successively, the pancreatic secretion was increased morethan the additive sum obtained by
基金the Innovation Studio from School of Biomedical Engineering,Shanghai Jiao Tong University,and the Medical-Engineering Cross Project of Shanghai Jiao Tong University(No.YG2017MS53)。
文摘Baroreflex plays a significant role in modulating blood pressure for the human body.It is known that activation of the vagal nerve related to baroreflex can lead to reductions of blood pressure.However,how the vagal activities quantitatively relate with blood pressure can hardly be achieved.Here fine carbon nanotube yarn(CNTy)electrodes were adopted for recording intrafascicular vagal activities,synchronized with measurement of arterial blood pressure in a rat.Together with a novel algorithm,the results preliminarily quantified that there were six clusters of neural spikes within recorded vagal activities,and the number of individual vagal spikes correspondingly varied with blood pressure.Especially for Cluster 2,the neural activations decreased with arterial blood pressure increasing.This study can shed lights on the quantified neural mechanism underlying the control of vagal activities on blood pressure,and guide the vagal-nerve neuromodulation for treating hypertension.
基金supported by the National Natural Science Foundation of China(30900646 and 81241004)
文摘Extracellular pH (pHe) and intracellular pH (pHi) are important factors for the excitability of chemosensitive central respiratory neurons that play an important role in respiration and obstructive sleep apnea. It has been proposed that inhibition of central Na+/ H+exchanger 3 (NHE-3), a key pH i regulator in the brainstem, decreases the pH i, leading to membrane depolarization for the maintenance of respiration. However, how intracellular pH affects the neuronal excitability of respiratory neurons remains largely unknown. In this study, we showed that NHE-3 mRNA is widely distributed in respiration-related neurons of the rat brainstem, including the dorsal vagal nucleus (DVN). Whole-cell patch clamp recordings from DVN neurons in brain slices revealed that the standing outward current (Iso) through pH-sensitive K+channels was inhibited in the presence of the specific NHE-3 inhibitor AVE0657 that decreased the pH i. Exposure of DVN neurons to an acidified pH e and AVE0657 (5 μmol/L) resulted in a stronger effect on firing rate and I so than acidified pH e alone. Taken together, our results showed that intracellular acidification by blocking NHE-3 results in inhibition of a pHsensitive K+current, leading to synergistic excitation of chemosensitive DVN neurons for the regulation of respiration.
文摘The glycemia-sensitive neuron in lateral hypothalamic area (LHA) is one of the important central neural events involved in the feeding control. Electrophysio-logical studies have demonstrated that gastrointestinal vagal afferent inputs could convey the meal-related information of gastrointestinal tract to the hypothalamus. In this study, we examined whether the gastric vagal afferent inputs could reach the glycemia-sensitive neurons of the LHA by using in vivo extracellular recording technique in the rat. The results showed that stimulation of gastric vagal nerves elicited two types of the LHA neurons responses: the phasic response (93/116, 80.2%) and the change in cells firing pattern (23/116, 19.8%). Within the 93 cells that responded to the gastric vagal stimulation with a phasic response, 67 (72.0%) showed an inhibition in the cells firing rate, 26 (27.4%) were excited. Of the 23 cells that showed a change in the firing pattern, 13 responded to the gastric vagal stimulation with a long-lasting increase or decrease in firing rate, the remaining 10 cells turned their discrete spiking to the burst discharging. In addition, of 101 LHA neurons including the two types of responsive neurons, 73 (72.3%) were identified to be glyce-mia-sensitive neurons. These results demonstrated that the gastric vagal afferent inputs could reach the LHA and pre-dominantly reach those glycemia-sensitive neurons in the LHA. Presumably, the modulation of glycemia-sensitive neurons of LHA by the gastric vagal afferent inputs may play an important role in the short-term regulation of feed-ing behavior.
文摘Recognizing the composition and modulation of the microbiome, a viable therapeutic tool for multi-targeted therapy is a new strategy that has recently been explored. Glucosamine (GS) is being studied for its prebiotic potential in addition to being the most abundant and naturally occurring amino monosaccharide. The current study focuses on glucosamine’s prebiotic potential by assessing the stability of various GS concentrations (1% - 5%) in the gastrointestinal tract (GIT) and its ability to be fermented by the gut microbiota. The results showed that GS stimulated the most growth in L. acidophilus even after a longer incubation time than B. bifidum and L. acidophilus growth was concentration-dependent, with maximum growth at 3% with a simultaneous decrease in pH (5.6 - 1.7). The decrease in GS concentration with time also represented the growth of bacterial species, demonstrating the species’ utilization of GS. Furthermore, at 3%, GS also represented the prebiotic index of 1.9. In addition, the concentration of GS in various simulated GIT fluids was estimated in both fast and fed conditions to examine GS stability at various levels in the gut. The results showed that GS remained unaffected and non-digestible in all of the simulated GIT fluids (salivary, gastric, intestinal, and colonic), but there was a slight decrease in GS concentration (2.8%) in the fasted state of gastric fluid due to low pH levels (1.6). As a result, the findings are conclusive and suggest that GS possesses prebiotic properties.
