Transcranial Direct Current Stimulation (tDCS) Ameliorates Stress-Induced Sleep Disruption via Activating Infralimbic-Ventrolateral Preoptic Projections.

Transcranial direct current stimulation (tDCS) is acknowledged for its non-invasive modulation of neuronal activity in psychiatric disorders. However, its application in insomnia research yields varied outcomes depending on different tDCS types and patient conditions. Our primary objective is to elucidate its efficiency and uncover the underlying mechanisms in insomnia treatment. We hypothesized that anodal prefrontal cortex stimulation activates glutamatergic projections from the infralimbic cortex (IL) to the ventrolateral preoptic area (VLPO) to promote sleep. After administering 0.06 mA of electrical currents for 8 min, our results indicate significant non-rapid eye movement (NREM) enhancement in naïve mice within the initial 3 h post-stimulation, persisting up to 16-24 h. In the insomnia group, tDCS enhanced NREM sleep bout numbers during acute stress response and improved NREM and REM sleep duration in subsequent acute insomnia. Sleep quality, assessed through NREM delta powers, remains unaffected. Interference of the IL-VLPO pathway, utilizing designer receptors exclusively activated by designer drugs (DREADDs) with the cre-DIO system, partially blocked tDCS's sleep improvement in stress-induced insomnia. This study elucidated that the activation of the IL-VLPO pathway mediates tDCS's effect on stress-induced insomnia. These findings support the understanding of tDCS effects on sleep disturbances, providing valuable insights for future research and clinical applications in sleep therapy.

A prolonged stress rat model recapitulates some PTSD-like changes in sleep and neuronal connectivity.

Chronic post-traumatic stress disorder (PTSD) exhibits psychological abnormalities during fear memory processing in rodent models. To simulate long-term impaired fear extinction in PTSD patients, we constructed a seven-day model with multiple prolonged stress (MPS) by modifying manipulation repetitions, intensity, and unpredictability of stressors. Behavioral and neural changes following MPS conveyed longitudinal PTSD-like effects in rats for 6 weeks. Extended fear memory was estimated through fear retrieval induced-freezing behavior and increased long-term serum corticosterone concentrations after MPS manipulation. Additionally, memory retrieval and behavioral anxiety tasks continued enhancing theta oscillation activity in the prefrontal cortex-basal lateral amygdala-ventral hippocampus pathway for an extended period. Moreover, MPS and remote fear retrieval stimuli disrupted sleep-wake activities to consolidate fear memory. Our prolonged fear memory, neuronal connectivity, anxiety, and sleep alteration results demonstrated integrated chronic PTSD symptoms in an MPS-induced rodent model.

Hypocretin role in posttraumatic stress disorder-like behaviors induced by a novel stress protocol in mice.

Introduction: Posttraumatic stress disorder (PTSD) is a psychiatric disorder developed in individuals who expose to traumatic events. These patients may experience symptoms, such as recurrent unwanted memory of the traumatic event, avoidance of reminders of the trauma, increased arousal, and cognitive difficulty. The hypocretinergic system originates from the lateral hypothalamic area (LHA) and projects diffusely to the whole brain, and hypocretin may be involved in the features of stress-related disorder, PTSD. Methods: Our study aimed to investigate the role of basolateral amygdala (BLA) hypocretin signals in the pathophysiology of PTSD-like symptoms induced by the modified multiple-prolonged stress (MPS) protocol. The BLA, a brain region involved in fear-related behaviors, receives the hypocretin projections. In this study, TCS1102, a dual hypocretin receptor antagonist, was used to block the hypocretin signal in BLA. Results: Our data indicated that the MPS protocol is a potential PTSD-like paradigm in mice. Meanwhile, the blockade of hypocretin signaling in the BLA relieved the MPS-induced fear response, and partially reduced PTSD-like anxiety behaviors performed by the open field test (OFT) and elevated plus maze (EPM) task. Discussion: Our findings suggest that the hypocretinergic system is a potential therapeutic approach for PTSD treatment. With further research, the hypocretin-based medication can be a candidate for human PTSD treatment.

Hypocretin in locus coeruleus and dorsal raphe nucleus mediates inescapable footshock stimulation (IFS)-induced REM sleep alteration.

Hypocretin (hcrt) is a stress-reacting neuropeptide mediating arousal and energy homeostasis. An inescapable footshock stimulation (IFS) could initiate the hcrt release from the lateral hypothalamus (LHA) and suppresses rapid eye movement (REM) sleep in rodents. However, the effects of the IFS-induced hcrts on REM-off nuclei, the locus coeruleus (LC) and dorsal raphe nucleus (DRN), remained unclear. We hypothesized that the hcrt projections from the LHA to LC or DRN mediate IFS-induced sleep disruption. Our results demonstrated that the IFS increased hcrt expression and the neuronal activities in the LHA, hypothalamus, brainstem, thalamus, and amygdala. Suppressions of REM sleep and slow wave activity during non-REM (NREM) sleep caused by the high expression of hcrts were blocked when a nonspecific and dual hcrt receptor antagonist was administered into the LC or DRN. Furthermore, the IFS also caused an elevated innate anxiety, but was limitedly influenced by the hcrt antagonist. This result suggests that the increased hcrt concentrations in the LC and DRN mediate stress-induced sleep disruptions and might partially involve IFS-induced anxiety.

Hericium erinaceus mycelium ameliorate anxiety induced by continuous sleep disturbance in vivo.

BACKGROUND: Sleep disruption is a major public health issue and may increase the risk of mortality by ten-folds if an individual is sleeping less than 6 h per night. Sleep has changed dramatically during to the COVID-19 pandemic because COVID symptoms can lead to psychological distress including anxiety. Hericium erinaceus mycelium has been widely investigated in both the in vivo studies and clinical trials for its neuroprotective functions because the mycelium contains hericenones and erinacines, which synthesize the nerve growth factor and brain-derived neurotrophic factor (BDNF). Recent in vivo reports have shown showed that erinacine A-enriched Hericium erinaceus mycelium can modulate BDNF/TrkB/PI3K/Akt/GSK-3ß pathways to induce an antidepressant-like effect. A large body of evidence indicates that erinacine can pass the blood-brain barrier and suggests its neuroprotective function in both peripheral and central nervous systems. Thus, Hericium erinaceus mycelium may be a dual-function supplement for sleep disruption improvement while sustaining anxiolytic effects. METHOD: To simulate the condition of sleep disruption, the mice were subjected to the tail suspension test (TST) for 15 min every day during the same period for nine consecutive days. Two different doses (75 and 150 mg/kg) of Hericium erinaceus mycelium were administered orally 20 min prior to the TSTs before entering the light period of 12:12 h L:D cycle. All sleep-wake recording was recorded for 24 h using electroencephalogram and electromyogram. The elevated-plus-maze and open-field tests were conducted to record the behavior activities. RESULTS: Consecutive TSTs prior to the light period could cause significant sleep disturbance and anxiety behavior in the elevated-plus-maze experiments. Results showed that administration with Hericium erinaceus mycelium at 150 mg/kg ameliorated the rodent anxiety (p < 0.05) and reversed the TST-induced NREM sleep disturbance in the dark period. CONCLUSION: This is the first in vivo study suggesting that Hericium erinaceus mycelium has a dual potential role for anxiety relief through improving sleep disruptions.

Disrupted Sleep Homeostasis and Altered Expressions of Clock Genes in Rats with Chronic Lead Exposure.

Sleep disturbance is one of the neurobehavioral complications of lead neurotoxicity. The present study evaluated the impacts of chronic lead exposure on alteration of the sleep-wake cycle in association with changes of clock gene expression in the hypothalamus. Sprague-Dawley rats with chronic lead exposure consumed drinking water that contained 250 ppm of lead acetate for five weeks. Electroencephalography and electromyography were recorded for scoring the architecture of the sleep-wake cycle in animals. At six Zeitgeber time (ZT) points (ZT2, ZT6, ZT10, ZT14, ZT18, and ZT22), three clock genes, including rPer1, rPer2, and rBmal1b, were analyzed. The rats with chronic lead exposure showed decreased slow wave sleep and increased wakefulness in the whole light period (ZT1 to ZT12) and the early dark period (ZT13 to ZT15) that was followed with a rebound of rapid-eye-movement sleep at the end of the dark period (ZT22 to ZT24). The disturbance of the sleep-wake cycle was associated with changes in clock gene expression that was characterized by the upregulation of rPer1 and rPer2 and the feedback repression of rBmal1b. We concluded that chronic lead exposure has a negative impact on the sleep-wake cycle in rats that predominantly disrupts sleep homeostasis. The disruption of sleep homeostasis was associated with a toxic effect of lead on the clock gene expression in the hypothalamus.

Perampanel Reduces Hyperthermia-Induced Seizures in Dravet Syndrome Mouse Model.

Treatment options for Dravet syndrome are limited. The aim of this study was to evaluate the antiepileptic effect of the AMPA receptor antagonist perampanel (PER) on a mouse model of Dravet syndrome (Scn1a E1099X/+ ). We report here that the PER (2 mg/kg) treatment inhibited the spontaneous recurrent seizures and attenuated epileptic activity in Scn1a E1099X/+ mice. In the hyperthermia-induced seizure experiment, PER clearly increased temperature tolerance and significantly ameliorated seizure frequency and discharge duration. PER also demonstrated antiepileptic effects in a cross-over study and a synergistic effect for attenuating heat-induced seizure when given in combination with stiripentol or valproic acid. The results showed that PER effectively decreased the occurrence of spontaneous recurrent seizures and showed significant therapeutic potential for hyperthermia-induced seizures with regard to both susceptibility and severity in a Dravet syndrome mouse model. Potential therapeutic effects of PER for treatment of Dravet syndrome were demonstrated.

Oral Administration of Armillaria mellea Mycelia Promotes Non-Rapid Eye Movement and Rapid Eye Movement Sleep in Rats.

The present study aimed to explore whether water and ethanol extracts of Armillaria mellea mycelia produce sedative and hypnotic effects in rats. Male Sprague-Dawley rats were surgically implanted with two electroencephalogram electrodes on the skull and an electromyogram electrode on neck muscle to evaluate the alterations in rapid eye movement (REM) and non-REM (NREM) sleep after oral administration of the water and ethanol extracts. Following post-surgical recovery, thirty-six rats were randomly divided into four treatment groups and two control groups. They were treated orally with vehicle, 75 and 150 mg/kg doses of water and ethanolic extracts 15 min prior to the onset of dark (active) period. Electroencephalography results showed that the low dose of A. mellea mycelia water extract increased REM sleep time while the high dose enhanced both REM and NREM sleep times during the subsequent light (rest) period. On the other hand, although the low dose of A. mellea mycelia ethanolic extract did not alter both NREM sleep and REM sleep during the dark and light periods, the high dose increased both REM and NREM sleep during the light periods in naive rats. The HPLC-DAD analyses of both extracts allowed the identification of GABA and seven sesquiterpenoids. Based on these findings, the present study showed for the first time that water and ethanolic extracts of A. mellea mycelia, containing a source of biologically active compounds, could increase both NREM sleep and REM sleep during the rest period and may be useful for the treatment of insomnia.

Pilot Study: Nutritional and Preclinical Safety Investigation of Fermented Hispidin-Enriched Sanghuangporus sanghuang Mycelia: A Promising Functional Food Material to Improve Sleep.

Sleep disturbances have been the hallmark of the recent coronavirus disease 2019 pandemic. Studies have shown that once sleep is disrupted, it can lead to psychological and physical health issues which can, in turn, disrupt circadian rhythm and induce further sleep disruption. As consumers are trying to establish healthy routines, nutritional and preclinical safety investigation of fermented hispidin-enriched Sanghuangporus sanghuang mycelia (GKSS) as a novel food material for spontaneous sleep in Sprague-Dawley rats is conducted for the first time. Results showed that the nutritional analysis of GKSS including moisture, ash, crude lipid, crude protein, carbohydrate, and energy were found to be 2.4 ± 0.3%, 8.0 ± 2.5%, 1.7 ± 0.3%, 22.9 ± 1.2%, 65.1 ± 3.1%, and 367.1 ± 10.2 kcal/100 g respectively. In the 28-day repeated-dose oral toxicity study, only Sprague-Dawley male rats receiving 5 g/kg showed a slight decrease in feed consumption at week 3, but no associated clinical signs of toxicity or significant weight loss were observed. Although a significant reduction of the platelet count was found in mid- and high-dose GKSS treated male groups, such changes were noted to be within the normal range and were not correlated with relative spleen weight changes. Hence, the no observed adverse effect level (NOAEL) of GKSS was identified to be higher than 5 g/kg in rats. After the safety of GKSS is confirmed, the sleep-promoting effect of GKSS ethanolic extract enriched with hispidin was further assessed. Despite 75 mg/kg of GKSS ethanolic extract does not affect wakefulness, rapid eye movement (REM) sleep and non-REM (NREM) sleep, GKSS ethanolic extract at 150 mg/kg significantly decreased wakefulness and enhanced NREM and REM sleep. Interestingly, such effects seem to be mediated through anti-inflammatory activities via NF-E2-related factor-2 (Nrf2) signaling pathway. Taken together, these findings provide the preliminary evidence to studies support the claims suggesting that GKSS contained useful phytochemical hispidin could be considered as and is safe to use as a functional food agent or nutraceutical for relieving sleep problems mediated by Nrf2 pathway, which the results are useful for future clinical pilot study.

Effects of N6 -(4-hydroxybenzyl) adenine riboside in stress-induced insomnia in rodents.

Adenosine exhibits a somnogenic effect; however, there is no adenosinergic hypnotic because of cardiovascular effects. This study investigated whether N6-(4-hydroxybenzyl) adenine riboside (T1-11), extracted from Gastrodia elata, produces somnogenic effects in rodents. We determined the involvement of adenosine 2A receptors (A2ARs) in GABAergic neurons of the ventrolateral preoptic area (VLPO) and the cardiovascular effects. Change of cage bedding is employed as a stressor to induce insomnia in rodents, and electroencephalograms and electromyograms were used to acquire and analyse sleep-wake activity. We found that intracerebroventricular administration of T1-11 before a dark period increased non-rapid eye movement (NREM) and rapid eye movement (REM) sleep during a dark period, and T1-11-induced sleep increases were blocked by the A2AR antagonist, SCH58261, in naïve rats. Oral administration of T1-11 increased NREM sleep during both dark and light periods. Microinjection of the A2AR antagonist, SCH58261, into the VLPO blocked sleep effects of T1-11. In addition to the somnogenic effect in naïve mice, T1-11 suppressed the stress-induced insomnia and this suppressive effect was blocked by SCH58261. C-fos expression in GABAergic neurons of VLPO was increased after administration of T1-11 in Gad2-Cre::Ai14 mice, suggesting the activation of GABAergic neurons in the VLPO. T1-11 exhibited no effects on heart rate and the low frequency/high frequency ratio of heart rate variability. We concluded that T1-11 elicited somnogenic effects and effectively ameliorated acute stress-induced insomnia. The somnogenic effect is mediated by A2ARs to activate GABAergic neurons in the VLPO. This adenosine analogue could be a potential hypnotic because of no sympathetic and parasympathetic effects on the cardiovascular system.

Connectivity between nidopallium caudolateral and visual pathways in color perception of zebra finches.

Researchers demonstrated an elegant ability for red discrimination in zebra finches. It is interested to understand whether red activates exhibit much stronger response than other colors in neural network levels. To reveal the question, local field potentials (LFPs) was recorded and analyzed in two visual pathways, the thalamofugal and the tectofugal pathways, of zebra finches. Human studies demonstrate visual associated telencephalons communicate with higher order brain areas such as prefrontal cortex. The present study determined whether a comparable transmission occurs in zebra finches. Telencephalic regions of the thalamofugal (the visual Wulst) and the tectofugal pathway (the entopallium) with their higher order telencephalon, nidopallium caudolateral (NCL) were simultaneously recorded. LFPs of relay nuclei (the nucleus rotundus, ROT) of tectofugal pathway were also acquired. We demonstrated that LFP powers in the tectofugal pathway were higher than those in the thalamofugal pathway when illuminating blue lights. In addition, the LFP synchronization was stronger between the entopallium and NCL. LFPs also revealed a higher Granger causality from the direction of entopallium to NCL and from ROT to entopallium. These results suggest that zebra finches' tectofugal pathway predominately processing color information from ROT to NCL, relayed by entopallium, and blue could trigger the strongest response.

Deep Brain Stimulation Increases Seizure Threshold by Altering REM Sleep and Delta Powers During NREM Sleep.

We previously demonstrated that seizure occurrences at different zeitgeber times alter sleep and circadian rhythm differently. On the other hand, the synchronized delta wave of electroencephalogram (EEG) during non-rapid eye movement (NREM) sleep facilitates seizure, while the desynchronized EEG of rapid eye movement (REM) sleep suppresses it. We also elucidated that unilateral deep brain stimulation (DBS) of the anterior nucleus of thalamus (ANT) suppresses seizure recurrence. In the present study, we intraperitoneally injected pentylenetetrazol (PTZ, 40 mg/kg) for 14 consecutive days (PTZ kindling) to induce spontaneous seizure in rats, and a 30-min (delivered 10 min before each PTZ injection) or a 3-h DBS of unilateral ANT (delivered 1 h before each PTZ injection) was applied to suppress seizure. The frequency of DBS stimulation was 200 Hz and the electrical current consisted of biphasic square pulses with 50-µA intensity, 100-µs pulse width, and 4.1-ms stimulation interval. Our results found that PTZ-induced spontaneous seizure did not cause a significant change in the quantity of NREM sleep but suppressed the amount of REM sleep. Unilateral ANT DBS prolonged the onset latency of ictal seizure, decreased the spontaneous seizure duration, and increased the survival rate but did not change the amplitude of epileptiform EEGs during ictal period. Unilateral ANT DBS did not significantly alter NREM sleep but increased the amount of REM sleep. An analysis of the spectrograms of fast Fourier transform indicated that the intensities of all frequencies were enhanced during the PTZ-induced ictal period and the subsequent spontaneous seizure. Thirty minutes of unilateral ANT DBS suppressed the augmentation of low-frequency (<10 Hz) intensities during the spontaneous seizure induced by PTZ kindling. We further found that consecutive injections of PTZ progressively increased the enhancement of the delta powers during NREM sleep, whereas unilateral ANT DBS inhibited this progressive enhancement. It was also noticed that 30 min of ANT DBS exhibited a better efficacy in epilepsy suppression than 3 h of ANT DBS. These results elucidated that unilateral ANT DBS enhanced the seizure threshold by increasing the amount of REM sleep and decreasing the progressive enhancement of delta power during NREM sleep to suppress spontaneous seizure recurrences in PTZ kindling-induced epileptic rats.

Hypocretin in median raphe nucleus modulates footshock stimuli-induced REM sleep alteration.

Stress is one of major factors that cause sleep problems. Hypocretin represents a stress-related neuropeptide and is well known in maintaining physiological wakefulness. The hypocretinergic neurons originate in the lateral hypothalamic area (LHA) and transmit to several brain regions, including the median raphe nuclei (MRNs). The MRNs modulate both fear responses and sleep-wake activity; however, it remains unclear whether stress alters the levels of hypocretin to regulate MRNs and consequently disrupt sleep. In this paper, we employed the inescapable footshock stimuli (IFS) as a stressor and hypothesized that the IFS-induced sleep disruption is mediated by increased hypocretins in the MRNs. Our results demonstrate that the concentrations of hypocretin in the hypothalamus increased after IFS. Rapid eye movement (REM) sleep was reduced after footshock, and microinjection of non-selective hypocretin receptor antagonist TCS-1102 into the MRNs blocked the IFS-induced decrease of REM sleep. Furthermore, administration of hypocretins into the MRNs mimicked the IFS-induced REM sleep reduction. These results conclude that the increased levels of hypocretins in the MRNs mediate the IFS-induced REM sleep reduction.

Pulsed radiofrequency stimulation suppresses palmar hyperhidrosis in an animal study.

Objectives: Palmar hyperhidrosis (PH) exhibits excessive and unpredictable sweating. The most effective treatment for permanent cure is the ablation of thoracic sympathetic ganglia innervating hands. However, sympathectomy of T2 sympathetic ganglion by clipping or cauterization causes irreversible nerve damage, and results in a compensatory hyperhidrosis (CH). We herein used the pulsed radiofrequency (PRF) stimulation to reversibly block sympathetic ganglion to treat PH and avoid CH. Material and Methods: A bipolar electrode was implanted into the right T2 sympathetic trunk by endoscopic surgery and PRF was delivered through the electrode. The humidity (%) of right palm was measured to indicate sweating level. Results: Six out of 13 rats (46.2%) that received a 5-min PRF stimulation on the T2 sympathetic trunk showed a decrease in the right palm humidity during the surgery. PRF stimulation significantly reduced humidity from 69.17% ± 0.72% obtained from baseline condition to 66.93% ± 0.69%. The humidity reduction was also observed at 10 min after the PRF stimulation. We further evaluated the effect of PRF stimulation 1 week after surgery and found that the PRF stimuli reduced right hand humidity in 5 out of 8 rats (62.5%). PRF stimulation significantly reduced humidity from 66.11% ± 0.81% obtained from sham operation control to 63.62% ± 0.82%. The percentage of right hand humidity obtained 10 min after PRF stimulation was also reduced to 63.38% ± 0.80%. Anesthetics have no effect on humidity. Conclusions: These results indicate that PRF stimulation of T2 sympathetic trunk reduces palm sweating in rats.

Interleukin-1 receptor (IL-1R) mediates epilepsy-induced sleep disruption.

BACKGROUND: Sleep disruptions are common in epilepsy patients. Our previous study demonstrates that homeostatic factors and circadian rhythm may mediate epilepsy-induced sleep disturbances when epilepsy occurs at different zeitgeber hours. The proinflammatory cytokine, interleukin-1 (IL-1), is a somnogenic cytokine and may also be involved in epileptogenesis; however, few studies emphasize the effect of IL-1 in epilepsy-induced sleep disruption. We herein hypothesized that IL-1 receptor type 1 (IL-1R1) mediates the pathogenesis of epilepsy and epilepsy-induced sleep disturbances. We determined the role of IL-1R1 by using IL-1R1 knockout (IL-1R1 -/- KO) mice. RESULTS: Our results elucidated the decrease of non-rapid eye movement (NREM) sleep during the light period in IL-1R -/- mice and confirmed the somnogenic role of IL-1R1. Rapid electrical amygdala kindling was performed to induce epilepsy at the particular zeitgeber time (ZT) point, ZT13. Our results demonstrated that seizure thresholds induced by kindling stimuli, such as the after-discharge threshold and successful kindling rates, were not altered in IL-1R -/- mice when compared to those obtained from the wildtype mice (IL-1R +/+ mice). This result suggests that IL-1R1 is not involved in kindling-induced epileptogenesis. During sleep, ZT13 kindling stimulation significantly enhanced NREM sleep during the subsequent 6 h (ZT13-18) in wildtype mice, and sleep returned to the baseline the following day. However, the kindling-induced sleep alteration was absent in the IL-1R -/- KO mice. CONCLUSIONS: These results indicate that the IL-1 signal mediates epilepsy-induced sleep disturbance, but dose not participate in kindling-induced epileptogenesis.

Manipulation of Epileptiform Electrocorticograms (ECoGs) and Sleep in Rats and Mice by Acupuncture.

Ancient Chinese literature has documented that acupuncture possesses efficient therapeutic effects on epilepsy and insomnia. There is, however, little research to reveal the possible mechanisms behind these effects. To investigate the effect of acupuncture on epilepsy and sleep, several issues need to be addressed. The first is to identify the acupoints, which correspond between humans, rats, and mice. Furthermore, the depth of insertion of the acupuncture needle, the degree of needle twist in manual needle acupuncture, and the stimulation parameters for electroacupuncture (EA) need to be determined. To evaluate the effects of acupuncture on epilepsy and sleep, a feasible model of epilepsy in rodents is required. We administer pilocarpine into the left central nucleus of the amygdala (CeA) to simulate focal temporal lobe epilepsy (TLE) in rats. Intraperitoneal (IP) injection of pilocarpine induces generalized epilepsy and status epilepticus (SE) in rats. Five IP injections of pentylenetetrazol (PTZ) with a one-day interval between each injection successfully induces spontaneous generalized epilepsy in mice. Recordings of electrocorticograms (ECoGs), electromyograms (EMGs), brain temperature, and locomotor activity are used for sleep analysis in rats, while ECoGs, EMGs, and locomotor activity are employed for sleep analysis in mice. ECoG electrodes are implanted into the frontal, parietal, and contralateral occipital cortices, and a thermistor is implanted above the cerebral cortex by stereotactic surgery. EMG electrodes are implanted into the neck muscles, and an infrared detector determines locomotor activity. The criteria for categorizing vigilance stages, including wakefulness, rapid eye movement (REM) sleep, and non-REM (NREM) sleep are based on information from ECoGs, EMGs, brain temperature, and locomotor activity. Detailed classification criteria are stated in the text.

Retrospective study of the clinical effects of acupuncture on cervical neurological diseases in dogs.

This study was conducted to evaluate new acupuncture protocols for the clinical treatment of cervical spinal cord diseases in 19 dogs. Three treatment options containing Jing-jiaji (cervical jiaji) were developed to treat neck pain, hemiparesis, and tetraparesis depending on the severity. The interval between the neurological disease onset and treatment (duration of signs), time to improvement after treatment, and recovery time were compared in dogs by body weight, age, and dry needle acupuncture (AP) with or without electro-AP (EAP). The duration of signs was longer in dogs weighing greater than 10 kg than in those weighing less than 10 kg (p＜ 0.05). Improvement and recovery times did not vary by body weight. Additionally, improvement and recovery times did not vary by age. The improvement and recovery times were longer in the AP+EAP group than the AP group (p＜ 0.05). Acupuncture with Jing-jiaji was effective in cervical spinal cord diseases in different sized dogs and in middle-aged and senior dogs. This report standardized AP treatment containing Jing-jiaji for canine cervical problems and evaluated its effects. The newly standardized AP methodology offers clinical practitioners an effective way to improve the outcomes of cervical neurological diseases in dogs.

Low-frequency electroacupuncture suppresses focal epilepsy and improves epilepsy-induced sleep disruptions.

BACKGROUND: The positive effects of acupuncture at Feng-Chi acupoints on treating epilepsy and insomnia have been well-documented in ancient Chinese literature. However, there is a lack of scientific evidence to elucidate the underlying mechanisms behind these effects. Our previous study demonstrated that high-frequency (100 Hz) electroacupuncture (EA) at Feng-Chi acupoints deteriorates both pilocarpine-induced focal epilepsy and sleep disruptions. This study investigated the effects of low-frequency (10 Hz) EA on epileptic activities and epilepsy-induced sleep disruptions. RESULTS: In rats, the Feng-Chi acupoint is located 3 mm away from the center of a line between the two ears. Rats received 30 min of 10 Hz EA stimuli per day before each day's dark period for three consecutive days. Our results indicated that administration of pilocarpine into the left CeA at the beginning of the dark period induced focal epilepsy and decreased both rapid eye movement (REM) sleep and non-REM (NREM) sleep during the consequent light period. Low-frequency (10 Hz) EA at Feng-Chi acupoints suppressed pilocarpine-induced epileptiform EEGs, and this effect was in turn blocked by naloxone (a broad-spectrum opioid receptor antagonist), but not by naloxonazine (a µ-receptor antagonist), naltrindole (a δ-receptor antagonist) and nor-binaltorphimine (a κ-receptor antagonist). Ten Hz EA enhanced NREM sleep during the dark period, and this enhancement was blocked by all of the opioid receptor antagonists. On the other hand, 10 Hz EA reversed pilocarpine-induced NREM suppression during the light period, and the EA's effect on the sleep disruption was only blocked by naloxonazine. CONCLUSIONS: These results indicate that low-frequency EA stimulation of Feng-Chi acupoints is beneficial in improving epilepsy and epilepsy-induced sleep disruptions, and that opioid receptors in the CeA mediate EA's therapeutic effects.

Functional and structural deficits of the dentate gyrus network coincide with emerging spontaneous seizures in an Scn1a mutant Dravet Syndrome model during development.

Dravet syndrome (DS) is characterized by severe infant-onset myoclonic epilepsy along with delayed psychomotor development and heightened premature mortality. A primary monogenic cause is mutation of the SCN1A gene, which encodes the voltage-gated sodium channel subunit Nav1.1. The nature and timing of changes caused by SCN1A mutation in the hippocampal dentate gyrus (DG) network, a core area for gating major excitatory input to hippocampus and a classic epileptogenic zone, are not well known. In particularly, it is still not clear whether the developmental deficit of this epileptogenic neural network temporally matches with the progress of seizure development. Here, we investigated the emerging functional and structural deficits of the DG network in a novel mouse model (Scn1a(E1099X/+)) that mimics the genetic deficit of human DS. Scn1a(E1099X/+) (Het) mice, similarly to human DS patients, exhibited early spontaneous seizures and were more susceptible to hyperthermia-induced seizures starting at postnatal week (PW) 3, with seizures peaking at PW4. During the same period, the Het DG exhibited a greater reduction of Nav1.1-expressing GABAergic neurons compared to other hippocampal areas. Het DG GABAergic neurons showed altered action potential kinetics, reduced excitability, and generated fewer spontaneous inhibitory inputs into DG granule cells. The effect of reduced inhibitory input to DG granule cells was exacerbated by heightened spontaneous excitatory transmission and elevated excitatory release probability in these cells. In addition to electrophysiological deficit, we observed emerging morphological abnormalities of DG granule cells. Het granule cells exhibited progressively reduced dendritic arborization and excessive spines, which coincided with imbalanced network activity and the developmental onset of spontaneous seizures. Taken together, our results establish the existence of significant structural and functional developmental deficits of the DG network and the temporal correlation between emergence of these deficits and the onset of seizures in Het animals. Most importantly, our results uncover the developmental deficits of neural connectivity in Het mice. Such structural abnormalities likely further exacerbate network instability and compromise higher-order cognitive processing later in development, and thus highlight the multifaceted impacts of Scn1a deficiency on neural development.

An Evaluation of Electroacupuncture at the Weizhong Acupoint (BL-40) as a Means of Relieving Pain Induced by Extracorporeal Shock Wave Lithotripsy.

Background. Extracorporeal shock wave lithotripsy (ESWL) is the preferred option for urolithiasis treatment. However, intensities of pain may be induced and the sedative anesthetic or analgesics were usually needed. The aim of this study was to develop an improved acupuncture-assisted anesthesia approach in pain relief. Methods. We conducted a single-blind, randomized controlled study in China Medical University Hospital. Patients treated by ESWL due to upper urolithiasis were randomly divided into control group, sham-EA group, and 100 Hz EA group. The high frequency electroacupuncture (EA) was applied at the Weizhong acupoint (100 Hz EA group) for 20 minutes prior to the ESWL. In the sham-EA group, the same procedures were performed as those of 100 Hz EA group but no electric current was given to stimulate the acupoints. In the control group, no action was taken before operation. The information including the numbers and dosage of analgesic requirements, pain score, vital signs, and the satisfaction of procedure was collected. Results. A total of 74 subjects were recruited and we found that the interval to the first request analgesic, the number/total dosage of additional analgesic, recovery time from anesthesia, and the satisfaction were all better in both the 100 Hz EA and the sham-EA group. The 100 Hz EA also showed better relief of painful sensations by delaying the onset of pain. Conclusions. The 100 Hz EA and the sham-EA can effectively relieve pain due to ESWL as well as reducing the dosage of opium analgesic used.