The zona incerta modulates spontaneous spike-wave discharges in the rat.

The contribution of the zona incerta (ZI) of the thalamus on spike-wave discharges (SWDs) was investigated. Chronic recordings of bilateral cortices, bilateral vibrissa muscle, and unilateral ZI were performed in Long-Evans rats to examine the functional role of SWDs. Rhythmic ZI activity appeared at the beginning of SWD and was accompanied by higher-oscillation frequencies and larger spike magnitudes. Bilateral lidocaine injections into the mystacial pads led to a decreased oscillation frequency of SWDs, but the phenomenon of ZI-related spike magnitude enhancement was preserved. Moreover, 800-Hz ZI microstimulation terminates most of the SWDs and whisker twitching (WT; >80%). In contrast, 200-Hz ZI microstimulation selectively stops WTs but not SWDs. Stimulation of the thalamic ventroposteriomedial nucleus showed no obvious effect on terminating SWDs. A unilateral ZI lesion resulted in a significant reduction of 7- to 12-Hz power of both the ipsilateral cortical and contralateral vibrissae muscle activities during SWDs. Intraincertal microinfusion of muscimol showed a significant inhibition on SWDs. Our present data suggest that the ZI actively modulates the SWD magnitude and WT behavior.

Acupuncture effect on dumping syndrome in esophagus cancer patients with feeding jejunostomy: A study protocol for a single blind randomized control trial.

INTRODUCTION: Esophagus cancer patients are at risk for malnourishment. Feeding jejunostomy is used in advanced esophagus cancer patients in order to support and supplement the patients' nutrition needs. In dumping syndrome, the food is rapidly introduced into the intestine at a rate that is faster than normal, it is associated with both digestive system and vasoactive symptoms. Dumping syndrome has an association with both esophagus cancer patients and feeding jejunostomy. In the mid and long term, dumping syndrome is an important issue that contributes to the risk of malnourishment in advanced esophagus cancer patients. In recent studies, acupuncture was effective in regulating digestive symptoms. Acupuncture is considered to be a safe intervention, that was previously shown to be effective in treating digestive-related symptoms. METHODS: Sixty advanced esophageal cancer patients post-feeding jejunostomy will be divided into 2 equal groups, an intervention group (n = 30) and a control group (n = 30). Patients in the intervention group will receive acupuncture using the following acupoints: ST36 (Zusanli), ST37 (Shangjuxu), ST39 (Xiajuxu), PC6 (Neiguan), LI4 (Hegu), and Liv 3 (Taichung). Patients in the control group will receive shallow acupuncture on 12 non-acupoints (sham points), 1 cm from the above mention points. Patients and assessors will be blind to trial allocation. Both groups will receive acupuncture twice a week for 6 weeks. The main outcome measurements are: body weight, BMI, Sigstad's score, and the Arts' dumping questionnaire. DISCUSSION: There are no previous studies that have examined the use of acupuncture on patients with dumping syndrome. This single-blind randomized control trial will investigate the effect of acupuncture on dumping syndrome in advanced esophagus cancer patients with feeding jejunostomy. The results will determine if verum acupuncture can affect dumping syndrome and prevent weight loss.

Involvement of the Cav3.2 T-type calcium channel in thalamic neuron discharge patterns.

BACKGROUND: Mice that have defects in their low-threshold T-type calcium channel (T-channel) genes show altered pain behaviors. The changes in the ratio of nociceptive neurons and the burst firing property of reticular thalamic (RT) and ventroposterior (VP) neurons in Cav3.2 knockout (KO) mice were studied to test the involvement of thalamic T-channel and burst firing activity in pain function. RESULTS: Under pentobarbital or urethane anesthesia, the patterns of tonic and burst firings were recorded in functionally characterized RT and VPL neurons of Cav3.2 KO mice. Many RT neurons were nociceptive (64% under pentobarbital anesthesia and 50% under urethane anesthesia). Compared to their wild-type (WT) controls, fewer nociceptive RT neurons were found in Cav3.2 KO mice. Both nociceptive and tactile RT neurons showed fewer bursts in Cav3.2 KO mice. Within a burst, RT neurons of Cav3.2 KO mice had a lower spike frequency and less-prominent accelerando-decelerando change. In contrast, VP neurons of Cav3.2 KO mice showed a higher ratio of bursts and a higher discharge rate within a burst than those of the WT control. In addition, the long-lasting tonic firing episodes in RT neurons of the Cav3.2 KO had less stereotypic regularity than their counterparts in WT mice. CONCLUSIONS: RT might be important in nociception of the mouse. In addition, we showed an important role of Cav3.2 subtype of T-channel in RT burst firing pattern. The decreased occurrence and slowing of the bursts in RT neurons might cause the increased VP bursts. These changes would be factors contributing to alternation of pain behavior in the Cav3.2 KO mice.

The protective effect of quercetin on retinal inflammation in mice: the involvement of tumor necrosis factor/nuclear factor-κB signaling pathways.

Quercetin is a natural flavonoid that occurs in fruits and vegetables. Retinal inflammation is an important cause of vision loss. This study was aimed to analyze the effects of oral administration of quercetin on retinal inflammation. Transgenic mice, carrying nuclear factor-κB (NF-κB)-driven luciferase genes, were injected with 1 mg per kg body weight of lipopolysaccharide (LPS). Various amounts (1, 10, and 100 mg per kg body weight) of quercetin were orally given to mice. LPS-induced retinal inflammation was evaluated by bioluminescence imaging and histological examination 4 hours later. RNA-Seq analysis of gene expression profiles was performed to explain the mechanisms of quercetin on eye inflammation. Our data showed that LPS enhanced luminescent signals on ocular tissues, while LPS-induced luminescence intensities were significantly suppressed by quercetin by 73.61 ± 21.74%. LPS significantly increased the thickness of retinal tissues by 1.52 ± 0.37 fold, in comparison with the mock, while quercetin reduced the LPS-induced retinal thickness and decreased the accumulation of infiltrating granulocytes. Biological pathway analysis showed that tumor necrosis factor (TNF), cytokine, and NF-κB signaling pathways were involved in the anti-inflammatory mechanisms of quercetin. Immunohistochemical staining further showed that quercetin reduced the activation of NF-κB, the expression of interleukin-1ß and TNF-α, and the infiltration of granulocytes in retinal tissues. In conclusion, this is the first study reporting the effects and mechanisms of orally administered quercetin against LPS-induced retinal inflammation in mice. Due to its safety, our study suggested that supplementation of quercetin has beneficial effects on the eyes.

Oral Administration of Vanillin Improves Imiquimod-Induced Psoriatic Skin Inflammation in Mice.

Vanillin is one of the most widely used flavoring products worldwide. Psoriasis is a chronic inflammatory skin disorder. The interleukin-23 (IL-23)/interleukin-17 (IL-17) axis plays a critical role in psoriasis. Here, we analyzed the effect of vanillin on imiquimod (IMQ)-induced psoriatic skin inflammation in mice. Mice were treated topically with IMQ on the back skin and orally with various amounts of vanillin for 7 consecutive days. Vanillin significantly improved IMQ-induced histopathological changes of skin in a dose-dependent manner. The thickness and number of cell layers of epidermis were reduced by 29 ± 14.4 and 27.8 ± 11%, respectively, in mice given 100 mg/kg of vanillin. A microarray showed that a total of 9042 IMQ-upregulated genes were downregulated by vanillin, and the biological pathways involved in the immune system and metabolism were significantly altered by vanillin. The upregulated expressions of IL-23, IL-17A, and IL-17F genes were suppressed by vanillin, with fold changes of -3.07 ± 0.08, -2.06 ± 0.21, and -1.62 ± 0.21, respectively. Moreover, vanillin significantly decreased both the amounts of IL-17A and IL-23 and the infiltration of immune cells in the skin tissues of IMQ-treated mice. In conclusion, our findings suggested that vanillin was an effective bioactive compound against psoriatic skin inflammation. Moreover, the downregulation of IL-23 and IL-17 expression suggested that vanillin was a novel regulator of the IL-23/IL-17 axis.

A simple method for fabricating microwire tetrode with sufficient rigidity and integrity without a heat-fusing process.

Heat-fusing is a common process for fabricating microwire tetrodes. However, it is time-consuming, and the high-temperature treatment can easily cause the insulation of the microwire to overheat leading to short circuits. We herein provide a simple, fast method to fabricate microwire tetrodes without the heat-fusion process. By increasing the twisting density, we were able to fabricate tetrodes with good rigidity and integrity. This kind of tetrode showed good recording quality, penetrated the brain surface easily, and remained intact after chronic implantation. This method requires only general laboratory tools and is relatively simple even for inexperienced workers.

Relation between activities of the cortex and vibrissae muscles during high-voltage rhythmic spike discharges in rats.

Paroxysmal 5- to 12-Hz high-voltage rhythmic spike (HVRS) activities, which are accompanied by whisker twitching (WT), are found in Long Evans rats, but the function of these HVRS activities is still debated. In four major functional hypotheses of HVRS discharges, i.e., alpha tremor, attention/mu rhythm, idling/mu rhythm, and absence seizure, the first two hypotheses emphasize WT behavior in HVRS bouts. Whisker movement is primarily determined by activation of intrinsic and extrinsic muscles. To clarify the role of WT in HVRS activities, simultaneous recording of the activities from the cortex and intrinsic/extrinsic and neck muscles were performed. Most HVRS bouts (68.8%) revealed no time-locked WT behavior in a 2-h recording session. In addition, WT primarily arose from active protraction due to activation of intrinsic muscles followed by passive retraction. A small portion of WT resulted from activation of both vibrissae muscles with dynamic frequency-dependent phase shifts. Onset of the rhythmic vibrissae EMG significantly lagged behind HVRS onset, and the mean duration of vibrissae muscle activity was one-third to a one-half of a HVRS bout. Moreover, a greater number of HVRS bouts were associated with a longer HVRS duration and higher oscillation frequency. Oscillation frequencies of HVRS activities without WT behavior were significantly lower than those with WT. Under peripheral sensory/motor blockade by xylocaine injection, oscillation frequencies of HVRS bouts significantly decreased, but no remarkable changes in the number or duration of HVRS bouts were observed. Compared with vibrissa muscle activity during WT and exploratory whisking, the duration of muscular activity in each cycle was apparently longer during whisking bouts. Based on these results, overemphasis of the role of WT on HVRS activities might not be appropriate. Instead, HVRS discharges may be associated with absence seizure or idling state. In addition, peripheral inputs, including WT, may elevate the oscillation frequency of HVRS bouts. Moreover, different muscular controls may exist between WT and whisking.