Carbachol increases locus coeruleus activation by targeting noradrenergic neurons, inhibitory interneurons and inhibitory synaptic transmission.

The locus coeruleus (LC) consists of noradrenergic (NA) neurons and plays an important role in controlling behaviours. Although much of the knowledge regarding LC functions comes from studying behavioural outcomes upon administration of muscarinic acetylcholine receptor (mAChR) agonists into the nucleus, the exact mechanisms remain unclear. Here, we report that the application of carbachol (CCh), an mAChR agonist, increased the spontaneous action potentials (sAPs) of both LC-NA neurons and local inhibitory interneurons (LC I-INs) in acute brain slices by activating M1/M3 mAChRs (m1/3 AChRs). Optogenetic activation of LC I-INs evoked inhibitory postsynaptic currents (IPSCs) in LC-NA neurons that were mediated by γ-aminobutyric acid type A (GABAA ) and glycine receptors, and CCh application decreased the IPSC amplitude through a presynaptic mechanism by activating M4 mAChRs (m4 AChRs). LC-NA neurons also exhibited spontaneous phasic-like activity (sPLA); CCh application increased the incidence of this activity. This effect of CCh application was not observed with blockade of GABAA and glycine receptors, suggesting that the sPLA enhancement occurred likely because of the decreased synaptic transmission of LC I-INs onto LC-NA neurons by the m4 AChR activation and/or increased spiking rate of LC I-INs by the m1/3 AChR activation, which could lead to fatigue of the synaptic transmission. In conclusion, we report that CCh application, while inhibiting their synaptic transmission, increases sAP rates of LC-NA neurons and LC I-INs. Collectively, these effects provide insight into the cellular mechanisms underlying the behaviour modulations following the administration of muscarinic receptor agonists into the LC reported by the previous studies.

Type of mandibular asymmetry affects changes and outcomes of bimaxillary surgery for class III asymmetry.

OBJECTIVES: Various methods have been used to classify class III asymmetry. There is little information on the use of an asymmetry index to examine soft tissue changes and outcomes for patients with class III asymmetry. This study aimed to (1) evaluate soft tissue changes and outcomes for three types of mandibular asymmetry and (2) determine if measures are associated with type of asymmetry. MATERIALS AND METHODS: Adults who consecutively underwent bimaxillary surgery using surgery-first approach for correction of class III asymmetry were divided into three groups based on type of mandibular asymmetry. This previously reported classification system is simple and mutually independent, categorizing mandibular asymmetry according to the amount and direction of ramus asymmetry relative to menton deviation: patients with a larger transverse ramus distance on the menton deviation side were divided into group 1 and group 2; group 1 (n = 45) exhibited a menton deviation larger than ramus discrepancy; group 2 (n = 11) exhibited a menton deviation less than ramus discrepancy; group 3 (n = 22) had larger transverse ramus distance contralateral to the side of the menton deviation. Soft tissue facial asymmetry indices, calculated from cone beam computed tomography images, assessed midline and contour asymmetry presurgery, changes postsurgery, and outcomes. RESULTS: Compared with groups 1 and 2, the presurgery index for contour and midline asymmetry was smallest for group 3. All the three groups had significant improvement in midline asymmetry postsurgery, and outcome measures were good; there were no differences between groups. However, contour asymmetry only improved significantly for groups 1 and 2. The outcome for contour asymmetry was fair for groups 1 and 3 and poor for group 2. CONCLUSIONS: Bimaxillary surgery significantly improved facial midline asymmetry. The type of mandibular asymmetry was associated with postsurgical changes and outcomes for contour asymmetry. CLINICAL RELEVANCE: Understanding the types of mandibular asymmetry could help clinicians to develop treatment plans and predict treatment changes and outcomes.

Inhibitory interneurons regulate phasic activity of noradrenergic neurons in the mouse locus coeruleus and functional implications.

KEY POINTS: The locus coeruleus (LC) contains noradrenergic (NA) neurons that respond to novel stimuli in the environment with phasic activation to initiate an orienting response; phasic LC activation is also triggered by stimuli, representing the outcome of task-related decision processes, to facilitate ensuing behaviours and help optimize task performance. Here, we report that LC-NA neurons exhibit bursts of action potentials in vitro resembling phasic LC activation in vivo, and the activity is gated by inhibitory interneurons (I-INs) located in the peri-LC. We also observe that inhibition of peri-LC I-INs enhances prepulse inhibition and axons from cortical areas that play important roles in evaluating the cost/reward of a stimulus synapse on both peri-LC I-INs and LC-NA neurons. The results help us understand the cellular mechanisms underlying the generation and regulation of phasic LC activation with a focus on the role of peri-LC I-INs. ABSTRACT: Noradrenergic (NA) neurons in the locus coeruleus (LC) have global axonal projection to the brain. These neurons discharge action potentials phasically in response to either novel stimuli in the environment to initiate an orienting behaviour or stimuli representing the outcome of task-related decision processes to facilitate ensuing behaviours and help optimize task performance. Nevertheless, the cellular mechanisms underlying the generation and regulation of phasic LC activation remain unknown. We report here that LC-NA neurons recorded in brain slices exhibit bursts of action potentials that resembled the phasic activation-pause profile observed in animals. The activity was referred to as phasic-like activity (PLA) and was suppressed and enhanced by blocking excitatory and inhibitory synaptic transmissions, respectively. These results suggest the existence of a local circuit to drive PLA, and the activity could be regulated by the excitatory-inhibitory balance of the circuit. In support of this notion, we located a population of inhibitory interneurons (I-INs) in the medial part of the peri-LC that exerted feedforward inhibition of LC-NA neurons through GABAergic and glycinergic transmissions. Selective inhibition of peri-LC I-INs with chemogenetic methods could enhance PLA in brain slices and increase prepulse inhibition in animals. Moreover, axons from the orbitofrontal and prelimbic cortices, which play important roles in evaluating the cost/reward of a stimulus, synapse on both peri-LC I-INs and LC-NA neurons. These observations demonstrate functional roles of peri-LC I-INs in integrating inputs of the frontal cortex onto LC-NA neurons and gating the phasic LC output.

GABAB receptor-mediated tonic inhibition regulates the spontaneous firing of locus coeruleus neurons in developing rats and in citalopram-treated rats.

KEY POINTS: Noradrenaline (NA)-releasing neurons in the locus coeruleus (LC) provide NA to the forebrain and play important roles in regulating many brain functions. LC neurons are subject to tonic inhibition mediated by GABAB receptors (GABAB Rs) and that the extent of the effect varies with ambient GABA levels. GABAB R-mediated tonic inhibition can effectively tune the spontaneous firing rate (SFR) of LC neurons; it is developmentally regulated and is responsible for maintaining a constant SFR of LC neurons during development. In male, but not female rats, chronic perinatal treatment with citalopram, a selective serotonin reuptake inhibitor, results in downregulation of GABAB R-mediated tonic inhibition of LC neurons that partially accounts for increased SFR in male, but not female, rats receiving such treatment. Our results show that GABAB R-mediated tonic inhibition could be an important player in the development of normal and abnormal behaviours/brain functions associated with the LC-NA system. Noradrenaline (NA)-releasing neurons in the locus coeruleus (LC) provide NA to the forebrain. Their activity is believed to be a key factor regulating the wakefulness/arousal level of the brain. In this study, we found that the activity of NA-releasing neurons in the LC (LC neurons) was subject to γ-aminobutyric acid (GABA) tonic inhibition through GABAB receptors (GABAB Rs), but not GABAA receptors. The intensity of GABAB R tonic inhibition was found to depend on ambient GABA levels, as it was dramatically increased by blockade of GABA reuptake. It also varied with the function of GABAB Rs. The GABAB R activity on LC neurons was found to increase with postnatal age up to postnatal days 8-10, resulting in increased tonic inhibition. Interestingly, there was no significant difference in the spontaneous activity of LC neurons at different postnatal ages unless GABAB R tonic inhibition was blocked. These results show that, during postnatal development, there is a continuous increase in GABAB R tonic inhibition that maintains the activity of LC neurons at a proper level. In male, but not female, rats, chronic perinatal treatment with citalopram, a selective serotonin reuptake inhibitor, reduced GABAB R activity and tonic inhibition, which might result in the significantly higher spontaneous activity of LC neurons seen in these animals. In conclusion, our results show that GABAB R-mediated tonic inhibition has a direct impact on the spontaneous activity of LC neurons and that the extent of the effect varies with ambient GABA levels and functionality of GABAB R signalling.

Knockdown of zebrafish blood vessel epicardial substance results in incomplete retinal lamination.

Cell polarity during eye development determines the normal retinal lamination and differentiation of photoreceptor cells in the retina. In vertebrates, blood vessel epicardial substance (Bves) is known to play an important role in the formation and maintenance of the tight junctions essential for epithelial cell polarity. In the current study, we generated a transgenic zebrafish Bves (zbves) promoter-EGFP zebrafish line to investigate the expression pattern of Bves in the retina and to study the role of zbves in retinal lamination. Immunostaining with different specific antibodies from retinal cells and transmission electron microscopy were used to identify the morphological defects in normal and Bves knockdown zebrafish. In normal zebrafish, Bves is located at the apical junctions of embryonic retinal neuroepithelia during retinogenesis; later, it is strongly expressed around inner plexiform layer (IPL) and retinal pigment epithelium (RPE). In contrast, a loss of normal retinal lamination and cellular polarity was found with undifferentiated photoreceptor cells in Bves knockdown zebrafish. Herein, our results indicated that disruption of Bves will result in a loss of normal retinal lamination.

Blood vessel epicardial substance (Bves) regulates epidermal tight junction integrity through atypical protein kinase C.

Bves is widely observed in the cell junction of the skin, epicardium, intestine, and cornea of both developmental embryos and mature adults. However, it is not clear how Bves confers its role in intercellular adhesion. Here, we identified the zebrafish bves (zBves) and found that the epidermal barrier function could be disrupted after knockdown of Bves, and these zBves morphants were sensitive to osmotic stress. A loss of zBves would affect the partitioning defective protein (PAR) junctional complex identified by the rescue experiment with tjp-2/ZO-2 or the PAR complex (par-3, par-6, and prkci/atypical (a)PKC) mRNAs, in which the survival rate of embryos increased 11, 24, 25, and 28%, respectively, after injection with junctional components; the tjp-2 and aPKC mRNA-rescued embryos also had 24 and 45% decreases in the defective rate. Immunofluorescent studies demonstrated that the aggregation of aPKC around the cell junctions had disintegrated in zBves morphants. However, the expression and assembly of zBves were not influenced by aPKC-MO. These results indicate that a loss of zBves affects the proteins involved in the pathway of the PAR junctional complex, especially aPKC, and both aPKC and Bves are indispensable to claudin expression.

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.

Protective effect of caffeic acid on paclitaxel induced anti-proliferation and apoptosis of lung cancer cells involves NF-κB pathway.

Caffeic acid (CA), a natural phenolic compound, is abundant in medicinal plants. CA possesses multiple biological effects such as anti-bacterial and anti-cancer growth. CA was also reported to induce fore stomach and kidney tumors in a mouse model. Here we used two human lung cancer cell lines, A549 and H1299, to clarify the role of CA in cancer cell proliferation. The growth assay showed that CA moderately promoted the proliferation of the lung cancer cells. Furthermore, pre-treatment of CA rescues the proliferation inhibition induced by a sub-IC(50) dose of paclitaxel (PTX), an anticancer drug. Western blot showed that CA up-regulated the pro-survival proteins survivin and Bcl-2, the down-stream targets of NF-κB. This is consistent with the observation that CA induced nuclear translocation of NF-κB p65. Our study suggested that the pro-survival effect of CA on PTX-treated lung cancer cells is mediated through a NF-κB signaling pathway. This may provide mechanistic insights into the chemoresistance of cancer calls.

Kynurenic acid attenuates multiorgan dysfunction in rats after heatstroke.

AIM: To assess whether systemic delivery of kynurenic acid improves the outcomes of heatstroke in rats. METHODS: Anesthetized rats were divided into 2 major groups and given vehicle solution (isotonic saline 0.3 mL/kg rat weight) or kynurenic acid (30-100 mg in 0.3 mL saline/kg) 4 h before the start of thermal experiments. They were exposed to an ambient temperature of 43 °C for 68 min to induce heatstroke. Another group of rats were exposed to room temperature (26 °C) and used as normothermic controls. Their core temperatures, mean arterial pressures, serum levels of systemic inflammatory response molecules, hypothalamic values of apoptotic cells and neuronal damage scores, and spleen, liver, kidney and lung values of apoptotic cells were determined. RESULTS: The survival time values during heatstroke for vehicle-treated rats were decreased from the control values of 475-485 min to new values of 83-95 min. Treatment with KYNA (30-100 mg/kg, iv) 4 h before the start of heat stress significantly and dose-dependently decreased the survival time to new values of 152-356 min (P<0.05). Vehicle-treated heatstroke rats displayed hypotension, hypothalamic neuronal degeneration and apoptosis, increased serum levels of tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and interleukin-10 (IL-10), and spleen, liver, kidney, and lung apoptosis. KYNA preconditioning protected against hypotension but not hyperthermia and attenuated hypothalamic neuronal degeneration and apoptosis during heatstroke. KYNA preconditioning attenuated spleen, kidney, liver, and lung apoptosis and up-regulated serum IL-10 levels but down-regulated serum TNF-α and ICAM-1 levels during heatstroke. CONCLUSION: Our results suggest that systemic delivery of kynurenic acid may attenuate multiorgan dysfunction in rats after heatstroke.

Mediation of vagal cardioinhibitory responses by glutamatergic receptors in the caudal medulla of turtles.

Our previous studies showed that electrical stimulation of the nuclei ambiguous (NA) or dorsomotor nuclei of the vagus (DMV) complex in the brain stem of spontaneously breathing pond turtles (Cyclemys fiavomarginata), anesthetized with chloralose (4 mg/100 g) and urethane (40 mg/100 g), produced a marked slowing or even cessation of the heart rate, and resulted in an immediate fall of blood pressure. Results of the present study further demonstrated that the cardioinhibitory responses could also be elicited by microinjection of monosodium glutamate (0.2-20 nl, 50 mM) into the NA/DMV complex in turtles. A two-barrel glass micropipette held in a manipulator was connected to a pneumatic pressure pump for microinjection. The glutamate-induced cardioinhibitory responses could be significantly reduced in a dose-dependent manner by pretreatment with AP-5 (a NMDA receptor antagonist, at 1-8 nmole) or CNQX (a non-NMDA receptor antagonist; at 0.1-0.8 nmole) 20 min before glutamate administration. Histochemical verification by injecting horseradish peroxidase into the cervical vagus nerves revealed that retrogradely labeled glutamatergic neurons in the NA/DMV complex were observed. These results suggest that glutamatergic receptors in the caudal medulla may mediate vagal cardioinhibitory responses in the turtle.

Smartphone-Based Artificial Intelligence-Assisted Prediction for Eyelid Measurements: Algorithm Development and Observational Validation Study.

BACKGROUND: Margin reflex distance 1 (MRD1), margin reflex distance 2 (MRD2), and levator muscle function (LF) are crucial metrics for ptosis evaluation and management. However, manual measurements of MRD1, MRD2, and LF are time-consuming, subjective, and prone to human error. Smartphone-based artificial intelligence (AI) image processing is a potential solution to overcome these limitations. OBJECTIVE: We propose the first smartphone-based AI-assisted image processing algorithm for MRD1, MRD2, and LF measurements. METHODS: This observational study included 822 eyes of 411 volunteers aged over 18 years from August 1, 2020, to April 30, 2021. Six orbital photographs (bilateral primary gaze, up-gaze, and down-gaze) were taken using a smartphone (iPhone 11 Pro Max). The gold-standard measurements and normalized eye photographs were obtained from these orbital photographs and compiled using AI-assisted software to create MRD1, MRD2, and LF models. RESULTS: The Pearson correlation coefficients between the gold-standard measurements and the predicted values obtained with the MRD1 and MRD2 models were excellent (r=0.91 and 0.88, respectively) and that obtained with the LF model was good (r=0.73). The intraclass correlation coefficient demonstrated excellent agreement between the gold-standard measurements and the values predicted by the MRD1 and MRD2 models (0.90 and 0.84, respectively), and substantial agreement with the LF model (0.69). The mean absolute errors were 0.35 mm, 0.37 mm, and 1.06 mm for the MRD1, MRD2, and LF models, respectively. The 95% limits of agreement were -0.94 to 0.94 mm for the MRD1 model, -0.92 to 1.03 mm for the MRD2 model, and -0.63 to 2.53 mm for the LF model. CONCLUSIONS: We developed the first smartphone-based AI-assisted image processing algorithm for eyelid measurements. MRD1, MRD2, and LF measures can be taken in a quick, objective, and convenient manner. Furthermore, by using a smartphone, the examiner can check these measurements anywhere and at any time, which facilitates data collection.

Striatal volume changes in a rat model of childhood attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common childhood neuropsychiatric disorders. Based on neuroimaging studies, the striatum is reported to be abnormal in size, but it is still not clear how they change during developmental stages. Spontaneously hypertensive rats (SHRs) are the commonly used animal model for ADHD. We investigated volume differences of the striatum at various ages before puberty in SHRs versus a control strain, Wistar-Kyoto rats (WKYs). Volumes of the bilateral striatum were measured using micrographs of Nissl-stained serial sections in both strains of rats at the ages of 4, 5, 6, 7, 8, 9, and 10weeks (n=4, each strain at each age). The results demonstrated that the age of a significant striatal volume difference between SHRs and WKYs was 5weeks; however, there was no significant difference for the corresponding total brain volume at each matched age. It suggested that the timing for striatal abnormalities in ADHD occurs during an early stage of childhood.

Extracellular Signal-Regulated Kinases Mediate an Autoregulation of GABAB-Receptor-Activated Whole-Cell Current in Locus Coeruleus Neurons.

The norepinephrine-releasing neurons in the locus coeruleus (LC) are well known to regulate wakefulness/arousal. They display active firing during wakefulness and a decreased discharge rate during sleep. We have previously reported that LC neurons express large numbers of GABAB receptors (GABABRs) located at peri-/extrasynaptic sites and are subject to tonic inhibition due to the continuous activation of GABABRs by ambient GABA, which is significantly higher during sleep than during wakefulness. In this study, we further showed using western blot analysis that the activation of GABABRs with baclofen could increase the level of phosphorylated extracellular signal-regulated kinase 1 (ERK1) in LC tissue. Recordings from LC neurons in brain slices showed that the inhibition of ERK1/2 with U0126 and FR180204 accelerated the decay of whole-cell membrane current induced by prolonged baclofen application. In addition, the inhibition of ERK1/2 also increased spontaneous firing and reduced tonic inhibition of LC neurons after prolonged exposure to baclofen. These results suggest a new role of GABABRs in mediating ERK1-dependent autoregulation of the stability of GABABR-activated whole-cell current, in addition to its well-known effect on gated potassium channels, to cause a tonic current in LC neurons.

GABAB receptor-mediated tonic inhibition of locus coeruleus neurons plays a role in deep anesthesia induced by isoflurane.

Noradrenergic neurons in the locus coeruleus referred to as locus coeruleus neurons, provide the major supply of norepinephrine to the forebrain and play important roles in behavior through regulation of wakefulness and arousal. In a previous study using brain slice preparations, we reported that locus coeruleus neurons are subject to tonic inhibition mediated by γ-aminobutyric acid B receptors (GABABRs) and that the extent of tonic inhibition varies with ambient GABA levels. Since ambient GABA in the locus coeruleus was reported to fluctuate during the sleep-wakefulness cycle, here we tested whether GABABR-mediated tonic inhibition of locus coeruleus neurons could be a mechanism underlying changes in brain arousal. We first demonstrated that GABABR-mediated tonic inhibition of locus coeruleus neurons also exists in vivo by showing that local infusion of CGP35348, a GABABR antagonist, into the locus coeruleus increased the firing rate of locus coeruleus neurons in anesthetized rats. We then showed that this manipulation accelerated the behavioral emergence of rats from deep anesthesia induced by isoflurane. Together, these observations show that GABABR-mediated tonic inhibition of locus coeruleus neurons occurs in vivo and support the idea that this effect may be important in regulating the functional state of the brain.

The correlation of mean sympathetic activity with low-frequency blood pressure and sympathetic variability.

The low-frequency (0.2-0.8 Hz) component of blood pressure (BP) variability (LF(BP)) is used as an index of the low-frequency variability of sympathetic nerve activity (SNA) (LF(SNA)) in rats. It is unclear whether the LF(BP) can be used as an index of the mean SNA (mSNA). We investigated the correlation of the LF(BP) with different levels of the mSNA in this study to evaluate if it is a feasible tool for detecting differences in mSNA under physiological conditions. Correlation of the LF(SNA) with different mSNA levels was also investigated. The BP and renal SNA of rats were recorded in a nonanesthetized state. Values of the mSNA obtained from 531 recording epochs in six rats were graded into 30 levels with a bin resolution of 0.05 normalized units. A linear regression analysis showed that the correlation between the mSNA and LF(SNA) was higher than that between the mSNA and LF(BP). The mSNA was well correlated with the LF(SNA) over a wider mSNA range, while it was correlated with the LF(BP) only in a restricted range. These results demonstrated a restricted condition under which measuring the LF(BP) can be a definitive index of the mSNA, and further suggest the possibility of using the weighted LF(BP) as an index of the mSNA via intermediation by the LF(SNA) for a wider mSNA range.

alpha-Phenyl-n-tert-butyl-nitrone attenuates lipopolysaccharide-induced brain injury and improves neurological reflexes and early sensorimotor behavioral performance in juvenile rats.

Our previous study showed that treatment with alpha-phenyl-n-tert-butyl-nitrone (PBN) after exposure to lipopolysaccharide (LPS) reduced LPS-induced white matter injury in the neonatal rat brain. The object of the current study was to further examine whether PBN has long-lasting protective effects and ameliorates LPS-induced neurological dysfunction. Intracerebral (i.c.) injection of LPS (1 mg/kg) was performed in postnatal day (P) 5 Sprague Dawley rat pups and PBN (100 mg/kg) or saline was administered intraperitoneally 5 min after LPS injection. The control rats were injected (i.c.) with sterile saline. Neurobehavioral tests were carried out from P3 to P21, and brain injury was examined after these tests. LPS exposure resulted in severe brain damage, including enlargement of ventricles bilaterally, loss of mature oligodendrocytes, impaired myelination as indicated by the decrease in myelin basic protein immunostaining, and alterations in dendritic processes in the cortical gray matter of the parietal cortex. Electron microscopic examination showed that LPS exposure caused impaired myelination as indicated by the disintegrated myelin sheaths in the juvenile rat brain. LPS administration also significantly affected neurobehavioral functions such as performance in righting reflex, wire hanging maneuver, cliff avoidance, negative geotaxis, vibrissa-elicited forelimb-placing test, beam walking, and gait test. Treatment with PBN, a free radical scavenger and antioxidant, provided protection against LPS-induced brain injury and associated neurological dysfunction in juvenile rats, suggesting that antioxidation might be an effective approach for therapeutic treatment of neonatal brain injury induced by infection/inflammation.

Primary cutaneous anaplastic large cell lymphoma of the face presenting as posttraumatic maxillary sinusitis.

Primary cutaneous anaplastic large cell lymphoma (ALCL) is an uncommon disease. It has various presentations that may mislead the diagnosis and cause delay of treatment. We report a 12-year-old boy who experienced persistent swollen and painful right cheek after blunt facial injury. The patient was first treated for maxillary sinusitis according to clinical history, but the pathology turned out to be primary cutaneous ALCL. Symptoms improved after chemotherapy with complete remission. No recurrence was noted during the follow-up period. The presentations of primary cutaneous ALCL of the face may mimic posttraumatic maxillary sinusitis. Any patient with facial prolonged symptoms or nonhealing wound should be excluded from this entity.

Frequency response characteristic of sympathetic mediated low-frequency blood pressure fluctuations in conscious rats.

A quantitative relationship between power densities of blood pressure (PBP) and sympathetic nerve activity (PSNA) in a low-frequency range (LF, 0.016-0.85 Hz), expressed as PSNA=PBPxax10bx(frequency) was proposed in pentobarbital-anesthetized rats. For evaluating the general applicability of this equation, the quantitative relationship of power density ratio Hf=PBP/PSNA across frequency was tested in a conscious state. Wistar rats were chronically instrumented with a femoral artery catheter and recording electrode around the renal sympathetic nerve. The blood pressure and renal sympathetic nerve activity were monitored both under pentobarbital anesthesia and in a conscious state. Linear regression analysis of the relationship between the frequency and logarithmic magnitude of the power density ratio in the LF range revealed excellent fit in both conditions (r=-0.96+/-0.01 and -0.93+/-0.01 for anesthetized and conscious rats, respectively). Comparing the regression lines, rats under pentobarbital anesthesia had significantly larger values for the y-intercept and slope compared to rats in a conscious state (y-intercepts: 0.80+/-0.09>0.53+/-0.08; slopes: -2.86+/-0.26>-1.62+/-0.21). Our results demonstrate that it is also feasible to use the weighted PBP in LF as a quantitative index of sympathetic variability in conscious rats, but the evaluation of possible complications controlling the regression parameters is called for.

A simple and effective process for noise reduction of multichannel cortical field potential recordings in freely moving rats.

Simple and useful steps, i.e. placing a grounded plate under the recording chamber as well as using multiple reference electrodes, are introduced here for obtaining reliable low-noise recordings of brain activity in freely moving rats. A general circuit model was built to analyze the electrical interference of both single-grounded and two-reference ground-free recording configurations. In both simulated and realistic conditions under two recording states, 60-Hz magnitude was in the microvolt range. Moreover, the noise was significantly reduced by shortening the distance between the subject and the grounded plate under the recording chamber. Furthermore, in chronically implanted rats, average 60-Hz interference of multichannel electroencephalograms of two-reference ground-free recordings (3.74 +/- 0.18 microV) was significantly smaller than that of the single-grounded condition (9.03 +/- 1.98 microV). Thus, we demonstrated that a lower-noise recording can be achieved by a two-reference configuration and a closely-placed metal grounded plate in an open-field circumstance. As compared to the use of a Faraday cage, this simple procedure is of benefit for long-term behavioral tracking with a video camera and for pharmacological experiments.

Neural and cardiac activities are altered by injection of picomoles of glutamate into the nucleus ambiguus of the rat.

A quantitative evaluation of the thresholds of changes in the firing rate/pattern and depolarizing block of the neuron and the bradycardiac response by pressure microinjection of 10 mM glutamate (Glu) into the region of the nucleus ambiguus (NA) of the ventral medulla was performed in anesthetized rats. A change in neuronal activity was shown with injection of about 2 pmol of Glu. A depolarizing block of single-unit activity could be observed at 2.9 +/- 0.3 nl (approximately 30 pmol, n = 22). Maximal bradycardiac response (-50 +/- 5%) was elicited with 4.4 +/- 0.7 nl (approximately 50 pmol, n = 10), which is significantly smaller than the ranges used in previous studies. Based on these results, a safe and effective use of 10 mM Glu to induce neuronal or physiological response should be in the range of a few nanoliters and less than 100 pmol, especially for the NA.