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Lundberg Y.W.,Boys Town National Research Hospital | Xu Y.,Boys Town National Research Hospital | Xu Y.,Shanghai Research Center for Acupuncture and Meridians | Thiessen K.D.,Creighton University | Kramer K.L.,Creighton University
Developmental Dynamics | Year: 2015

Otoconia are bio-crystals that couple mechanic forces to the sensory hair cells in the utricle and saccule, a process essential for us to sense linear acceleration and gravity for the purpose of maintaining bodily balance. In fish, structurally similar bio-crystals called otoliths mediate both balance and hearing. Otoconia abnormalities are common and can cause vertigo and imbalance in humans. However, the molecular etiology of these illnesses is unknown, as investigators have only begun to identify genes important for otoconia formation in recent years. Results: To date, in-depth studies of selected mouse otoconial proteins have been performed, and about 75 zebrafish genes have been identified to be important for otolith development. Conclusions: This review will summarize recent findings as well as compare otoconia and otolith development. It will provide an updated brief review of otoconial proteins along with an overview of the cells and cellular processes involved. While continued efforts are needed to thoroughly understand the molecular mechanisms underlying otoconia and otolith development, it is clear that the process involves a series of temporally and spatially specific events that are tightly coordinated by numerous proteins. Such knowledge will serve as the foundation to uncover the molecular causes of human otoconia-related disorders. © 2014 Wiley Periodicals, Inc.


Gu Q.,Shanghai Research Center for Acupuncture and Meridians | Gu Q.,Shanghai University of Traditional Chinese Medicine | Wang L.,Shanghai Research Center for Acupuncture and Meridians | Huang F.,Fudan University | And 2 more authors.
Evidence-based Complementary and Alternative Medicine | Year: 2012

Low-level laser irradiation of visible light had been introduced as a medical treatment already more than 40 years ago, but its medical application still remains controversial. Laser stimulation of acupuncture points has also been introduced, and mast-cells degranulation has been suggested. Activation of TRPV ion channels may be involved in the degranulation. Here, we investigated whether TRPV1 could serve as candidate for laser-induced mast cell activation. Activation of TRPV1 by capsaicin resulted in degranulation. To investigate the effect of laser irradiation on TRPV1, we used the Xenopus oocyte as expression and model system. We show that TRPV1 can functionally be expressed in the oocyte by (a) activation by capsaicin (K1/2 = 1.1 M), (b) activation by temperatures exceeding 42°C, (c) activation by reduced pH (from 7.4 to 6.2), and (d) inhibition by ruthenium red. Red (637 nm) as well as blue (406 nm) light neither affected membrane currents in oocytes nor did it modulate capsaicin-induced current. In contrast, green laser light (532 nm) produced power-dependent activation of TRPV1. In conclusion, we could show that green light is effective at the cellular level to activate TRPV1. To which extend green light is of medical relevance needs further investigation. © 2012 Quanbao Gu et al.


Zhou F.,Shanghai Research Center for Acupuncture and Meridians | Zhou F.,Gongli Hospital | Guo J.,Fudan University | Cheng J.,Fudan University | And 4 more authors.
Evidence-based Complementary and Alternative Medicine | Year: 2013

Electroacupuncture (EA) has been shown to increase cerebral blood flow (CBF) and reduce ischemic infarction in the rat model of cerebral ischemia (middle cerebral artery occlusion, MCAO). Since multiple acupoints are recommended to treat cerebral ischemia, we performed this study to investigate if there is any variation in EA protection against cerebral ischemia with the stimulation of certain "acupoints" in rats. One hour of right MCAO with an 85% reduction of blood flow induced an extensive infarction (32.9% ± 3.8% of the brain), serious neurological deficits (scale = 6.0 ± 0.5, on a scale of 0-7), and a 17% (10 out of 60) mortality. EA, with a sparse-dense wave (5 Hz/20 Hz) at 1.0 mA for 30 minutes, at Du 20 and Du 26 greatly reduced the infarction to 4.5% ± 1.5% (P<0.01), significantly improved neurological deficit (scale = 1.0 ± 0.5, P<0.01), and decreased the death rate to 7% (2 out of 30, P<0.01). Similarly, EA at left LI 11 & PC 6 reduced the infarct volume to 8.6% ± 3.8% (P<0.01), improved the neurological deficit (scale = 2.0 ± 1.0, P<0.01), and decreased the death rate to 8% (2 out of 24, P<0.01). In sharp contrast, EA at right LI 11 & PC 6 did not lead to any significant changes in the infarct volume (33.4% ± 6.3%), neurological deficit (scale = 6.5 ± 0.5), and the death rate (20%, 5 out of 24). EA at left GB 34 & SP 6, also had an inconspicuous effect on the ischemic injury. EA at Du 20 & Du 26 or at left LI 11 & PC 6 instantaneously induced a significant increase in cerebral blood flow. Neither EA at right LI 11 & PC 6 nor at GB 34 & SP 6 increased cerebral blood flow. These results revealed that the EA protection against cerebral ischemia is relatively acupoint specific. © 2013 Fei Zhou et al.


Friedemann T.,Shanghai Research Center for Acupuncture and Meridians | Friedemann T.,Goethe University Frankfurt | Shen X.,Shanghai University of Traditional Chinese Medicine | Bereiter-Hahn J.,Goethe University Frankfurt | Schwarz W.,Shanghai Research Center for Acupuncture and Meridians
Lasers in Medical Science | Year: 2012

Physical stimulation of body surface points is known to affect various organ functions. In traditional Chinese medicine, so-called acupoints were defined. These points can be physically stimulated to effectively treat various diseases. Here we describe for the first time the effect of CO2 laser stimulation at the acupoints Neiguan (PC-6), Quchi (LI-11), Zusanli (ST-36), and Taichong (LR-3) on heart rate and mean arterial blood pressure in anesthetized rats. CO2 laser stimulation increased the skin surface temperature to 54°C. Our results revealed that the laser stimulation at the left or right PC-6 and LR-3 increased heart rate and mean arterial pressure. There was no response of heart rate and mean arterial pressure during and after stimulation of the left LI-11, but laser stimulation at the right LI-11 slightly increased heart rate and mean arterial pressure. On the other hand, laser stimulation at the left and right ST-36 decreased heart rate and mean arterial pressure. The effects on mean arterial pressure were more pronounced than those on heart rate. After full spinal cord transection, all heart-rate and mean-arterial-pressure responses were attenuated or completely abolished. These results suggest that CO2 laser stimulation at either the left or right PC-6, ST-36, and LR-3, as well as at the right LI-11 can modulate the cardiovascular functions in anesthetized rats, and its modulatory site might be supraspinal. © 2011 Springer-Verlag London Ltd.


Chao D.,University of Houston | Chao D.,Yale University | Chao D.,Shanghai Research Center for Acupuncture and Meridians | Shen X.,Shanghai Research Center for Acupuncture and Meridians | And 3 more authors.
Evidence-based Complementary and Alternative Medicine | Year: 2013

Epilepsy is one of the most common neurological disorders affecting about 1% of population. Although the precise mechanism of its pathophysiological changes in the brain is unknown, epilepsy has been recognized as a disorder of brain excitability characterized by recurrent unprovoked seizures that result from the abnormal, excessive, and synchronous activity of clusters of nerve cells in the brain. Currently available therapies, including medical, surgical, and other strategies, such as ketogenic diet and vagus nerve stimulation, are symptomatic with their own limitations and complications. Seeking new strategies to cure this serious disorder still poses a big challenge to the field of medicine. Our recent studies suggest that acupuncture may exert its antiepileptic effects by normalizing the disrupted neuronal and network excitability through several mechanisms, including lowering the overexcited neuronal activity, enhancing the inhibitory system, and attenuating the excitatory system in the brain via regulation of the interaction between δ-opioid receptors (DOR) and Na+ channels. This paper reviews the progress in this field and summarizes new knowledge based on our work and those of others. © 2013 Dongman Chao et al.


Tian X.,Fudan University | Tian X.,University of Houston | Guo J.,Fudan University | Guo J.,Shanghai Research Center for Acupuncture and Meridians | And 4 more authors.
PLoS ONE | Year: 2013

Objectives:δ-opioid receptor (DOR) activation reduced brain ischemic infarction and attenuated neurological deficits, while DOR inhibition aggravated the ischemic damage. The underlying mechanisms are, however, not well understood yet. In this work, we asked if DOR activation protects the brain against ischemic injury through a brain-derived neurotrophic factor (BDNF) -TrkB pathway.Methods:We exposed adult male Sprague-Dawley rats to focal cerebral ischemia, which was induced by middle cerebral artery occlusion (MCAO). DOR agonist TAN-67 (60 nmol), antagonist Naltrindole (100 nmol) or artificial cerebral spinal fluid was injected into the lateral cerebroventricle 30 min before MCAO. Besides the detection of ischemic injury, the expression of BDNF, full-length and truncated TrkB, total CREB, p-CREB, p-ATF and CD11b was detected by Western blot and fluorescence immunostaining.Results:DOR activation with TAN-67 significantly reduced the ischemic volume and largely reversed the decrease in full-length TrkB protein expression in the ischemic cortex and striatum without any appreciable change in cerebral blood flow, while the DOR antagonist Naltrindole aggregated the ischemic injury. However, the level of BDNF remained unchanged in the cortex, striatum and hippocampus at 24 hours after MCAO and did not change in response to DOR activation or inhibition. MCAO decreased both total CREB and pCREB in the striatum, but not in the cortex, while DOR inhibition promoted a further decrease in total and phosphorylated CREB in the striatum and decreased pATF-1 expression in the cortex. In addition, MCAO increased C11b expression in the cortex, striatum and hippocampus, and DOR activation specifically attenuated the ischemic increase in the cortex but not in the striatum and hippocampus.Conclusions:DOR activation rescues TrkB signaling by reversing ischemia/reperfusion induced decrease in the full-length TrkB receptor and reduces brain injury in ischemia/reperfusion. © 2013 Tian et al.


Zhou F.,Shanghai Research Center for Acupuncture and Meridians | Zhou F.,Gongli Hospital | Guo J.,Fudan University | Cheng J.,Fudan University | And 3 more authors.
Evidence-based Complementary and Alternative Medicine | Year: 2013

We explored the optimal duration of electroacupuncture (EA) stimulation for protecting the brain against ischemic injury. The experiments were carried out in rats exposed to right middle cerebral artery occlusion (MCAO) for 60 min followed by 24-hr reperfusion. EA was delivered to "Shuigou" (Du 26) and "Baihui" (Du 20) acupoints with sparse-dense wave (5/20 Hz) at 1.0 mA for 5, 15, 30, and 45 min, respectively. The results showed that 30 min EA, starting at 5 minutes after the onset of MCAO (EA during MCAO) or 5 minutes after reperfusion (EA after MCAO), significantly reduced ischemic infarct volume, attenuated neurological deficits, and decreased death rate with a larger reduction of the ischemic infarction in the former group. Also in the group of EA during MCAO, this protective benefit was positively proportional to the increase in the period of stimulation, that is, increased protection in response to EA from 5- to 30-min stimulation. In all groups, EA induced a significant increase in cerebral blood flow and promoted blood flow recovery after reperfusion, and both blood flow volume and blood cell velocity returned to the preischemia level in a short period of time. Surprisingly, EA for 45 min did not show reduction in the neurological deficits or the infarct volume and instead demonstrated an increase in death rate in this group. Although EA for 45 min still increased the blood flow during MCAO, it led to a worsening of perfusion after reperfusion compared to the group subjected only to ischemia. The neuroprotection induced by an "optimal" period (30 min) of EA was completely blocked by Naltrindole, a δ-opioid receptor (DOR) antagonist (10 mg/kg, i.v.). These findings suggest that earlier EA stimulation leads to better outcomes, and that EA-induced neuroprotection against ischemia depends on an optimal EA-duration via multiple pathways including DOR signaling, while "over-length" stimulation exacerbates the ischemic injury. © 2013 Fei Zhou et al.


Kang X.,Shanghai Research Center for Acupuncture and Meridians | Kang X.,Shanghai University of Traditional Chinese Medicine | Shen X.,Shanghai Research Center for Acupuncture and Meridians | Shen X.,Shanghai University of Traditional Chinese Medicine | And 2 more authors.
Evidence-based Complementary and Alternative Medicine | Year: 2013

The efficacy of electroacupuncture (EA) on epilepsy remains to be verified because of previous controversies that might be due to the complexity of the effects induced by different acupoints and stimulation approaches adopted. Therefore, we investigated the effects of EA on epilepsy to determine the specific acupoints and optimal stimulation parameters in this work. Experimental epilepsy was induced by injecting kainic acid to the lateral cerebral ventricle of adult male SD rats. EA with a low-frequency (10 Hz/1 mA) or high-frequency (100 Hz/1 mA) current was applied to the epileptic model for 30 minutes starting at 0.5 hour after the injection. Four pairs of acupoints were tested, that is, Shuigou (DU26) + Dazhui (DU14), Jinsuo (DU8) + Yaoqi (EXB9), Neiguan (PC6) + Quchi (LI11), and Fenglong (ST40) + Yongquan (KI1). We found that (1) low- or high-frequency EA at different acupoints reduced epileptic seizures (P<0.05 versus the control) with an exception of low-frequency EA at Neiguan (PC6) and Quchi (LI11); (2) low-frequency EA induced a better effect at Fenglong (ST40) plus Yongquan (KI1) than that of the other acupoints (P<0.05); (3) there is no significant difference in the effects of high-frequency EA at these acupoints; and (4) the high-frequency EA elicited a greater effect than that of low-frequency EA in all groups (P<0.05), with an exception at Jinsuo (DU8) + Yaoqi (EXB9). The EA-induced attenuation appeared 1-1.5 hours after EA with no appreciable effect in the first hour after EA in either the EEG or the behavioral tests. We conclude that EA attenuation of epileptic seizures is dependent on the stimulation parameters and acupoints and that the delay in appearance of the EA effect could be a reflection of the time required by the EA signal to regulate neural function in the central nervous system. © 2013 Xuezhi Kang et al.


Zhou F.,Shanghai Research Center for Acupuncture and Meridians | Guo J.,Fudan University | Cheng J.,Fudan University | Wu G.,Fudan University | And 2 more authors.
Journal of Applied Physiology | Year: 2011

Stroke causes ischemic brain injury and is a leading cause of neurological disability and death. There is, however, no promising therapy to protect the brain from ischemic stress to date. Here we show an exciting finding that optimal electroacupuncture (EA) effectively protects the brain from ischemic injury. The experiments were performed on rats subjected to middle cerebral artery occlusion (MCAO) with continuous monitoring of cerebral blood flow. EA was delivered to acupoints of "Shuigou" (Du 26) and "Baihui" (Du 20) with different intensities and frequencies to optimize the stimulation parameters. The results showed that 1) EA at 1.0-1.2 mA and 5-20 Hz remarkably reduced ischemic infarction, neurological deficit, and death rate; 2) the EA treatment increased the blood flow by>100%, which appeared immediately after the initiation of EA and disappeared after the cessation of EA; 3) the EA treatment promoted the recovery of the blood flow after MCAO; 4) "nonoptimal" parameters of EA (e.g., <0.6 mA or >40 Hz) could not improve the blood flow or reduce ischemic injury; and 5) the same EA treatment with optimal parameters could not increase the blood flow in naive brains. These novel observations suggest that appropriate EA treatment protects the brain from cerebral ischemia by increasing blood flow to the ischemic brain region via a rapid regulation. Our findings have far-reaching impacts on the prevention and treatment of ischemic encephalopathy, and the optimized EA parameters may potentially be a useful clue for the clinical application of EA. Copyright © 2011 the American Physiological Society.


Wang Z.-J.,Fudan University | Li W.-M.,Fudan University | Li W.-M.,Shanghai Research Center for Acupuncture and Meridians
Journal of Chinese Integrative Medicine | Year: 2010

Objective: To investigate the effects of electroacupuncture (EA) on intestinal motility disorder in rats with irritable bowel syndrome (IBS) in order to provide experimental evidence for improving clinical treatment to IBS with EA. Methods: IBS was induced by inserting a balloon into the rectum of male Sprague-Dawley rats from their neonatal age (8th, 21st day after birth) and applying colorectal distention stimulation by inflating air into the balloon. Peristaltic wave (PW) was used to estimate intestinal motility. Rats were divided into 4 groups (n = 6): normal group, untreated group, sham EA group and EA group. Acupoints of Zusanli (ST36) and Shangjuxu (ST37) in the hind limbs bilaterally were chosen for EA and sham EA treatment. Trains of dense-sparse frequencies (100 Hz and 2 Hz alternately) and intensity of 1, 2 and 3 mA (10 min for each) were applied for 30 min with each EA treatment while inserting similar needles without electrical stimulation was done as sham EA treatment. PW recorded for 30 min in normal and untreated groups respectively was taken as control values, while PW recorded after EA or sham EA treatment for 30 min was taken as responsive values. Results: Frequency of PW was significantly increased in the untreated group as compared with that in the normal group (P<0.05), and decreased after 30-min EA treatment ( P < 0.05). There was no significant change in the PW of sham EA group as compared with the control group and before treatment (P>0.05). Conclusion: These results suggest that 1) there is an abnormal increase in intestinal motility indicating an intestinal motility disorder in IBS rats; 2) EA but not sham EA can relieve such intestinal motility disorder.

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