Tripolar Electrode Research Articles

Neuronal rhythmicity and cortical arousal in a mouse model of absence epilepsy

Objectives: Absence seizures impair psychosocial function, yet their detailed neuronal basis remains unknown. Recent work in a rat model suggests that cortical arousal state changes prior to seizures and that single neurons show diverse firing patterns during seizures. Our aim was to extend these investigations to a mouse model with studies of neuronal activity and arousal state to facilitate future fundamental investigations of absence epilepsy.Methods: We performed in vivo extracellular single unit recordings on awake head-fixed C3H/HeJ mice. Mice were implanted with tripolar electrodes for cortical electroencephalography (EEG). Extracellular single unit recordings were obtained with glass micropipettes in the somatosensory barrel cortex, while animals ambulated freely on a running wheel. Signals were digitized and analyzed during seizures and at baseline.Results: Neuronal activity was recorded from 36 cortical neurons in 19 mice while EEG showed characteristic 7–8 Hz spike-wave discharges. Different single neurons showed distinct firing patterns during seizures, but the overall mean population neuronal firing rate during seizures was no different from pre-seizure baseline. However, the rhythmicity of neuronal firing during seizures was significantly increased (p < 0.001). In addition, beginning 10s prior to seizure initiation, we observed a progressive decrease in cortical high frequency (>40 Hz) EEG and an increase in lower frequency (1–39 Hz) activity suggesting decreased arousal state.Significance: We found that the awake head-fixed C3H/HeJ mouse model demonstrated rhythmic neuronal firing during seizures, and a decreased cortical arousal state prior to seizure onset. Unlike the rat model we did not observe an overall decrease in neuronal firing during seizures. Similarities and differences across species strengthen the ability to investigate fundamental key mechanisms. Future work in the mouse model will identify the molecular basis of neurons with different firing patterns, their role in seizure initiation and behavioral deficits, with ultimate translation to human absence epilepsy.

Effect of the closed-loop hippocampal low-frequency stimulation on seizure severity, learning, and memory in pilocarpine epilepsy rat model.

In this study, the anticonvulsant action of closed-loop, low-frequency deep brain stimulation (DBS) was investigated. In addition, the changes in brain rhythms and functional connectivity of the hippocampus and prefrontal cortex were evaluated. Epilepsy was induced by pilocarpine in male Wistar rats. After the chronic phase, a tripolar electrode was implanted in the right ventral hippocampus and a monopolar electrode in medial prefrontal cortex (mPFC). Subjects' spontaneous seizure behaviors were observed in continuous video recording, while the local field potentials (LFPs) were recorded simultaneously. In addition, spatial memory was evaluated by the Barnes maze test. Applying hippocampal DBS, immediately after seizure detection in epileptic animals, reduced their seizure severity and duration, and improved their performance in Barnes maze test. DBS reduced the increment in power of delta, theta, and gamma waves in pre-ictal, ictal, and post-ictal periods. Meanwhile, DBS increased the post-ictal-to-pre-ictal ratio of theta band. DBS decreased delta and increased theta coherences, and also increased the post-ictal-to-pre-ictal ratio of coherence. In addition, DBS increased the hippocampal-mPFC coupling in pre-ictal period and decreased the coupling in the ictal and post-ictal periods. Applying closed-loop, low-frequency DBS at seizure onset reduced seizure severity and improved memory. In addition, the changes in power, coherence, and coupling of the LFP oscillations in the hippocampus and mPFC demonstrate low-frequency DBS efficacy as an antiepileptic treatment, returning LFPs to a seemingly non-seizure state in subjects that received DBS.

The role of HCN channels on the effects of T-type calcium channels and GABAA receptors in the absence epilepsy model of WAG/Rij rats.

In this study we used ivabradine (IVA), a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker, to identify its effect on spike-wave discharges (SWDs); and aimed to determine the role of IVA on the effects of T-type calcium channel blocker NNC 55-0396, GABAA receptor agonist muscimol and antagonist bicuculline in male WAG/Rij rats. After tripolar electrodes for electrocorticogram (ECoG) recordings were placed on the WAG/Rij rats' skulls, 5, 10, and 20 mg/kg IVA were intraperitoneally administered for 7 consecutive days and ECoG recordings were obtained on days 0th, 3rd, 6th, and 7th for threehours before and after injections. While acute injection of 5, 10, and 20 mg/kg IVA did not affect the total number and the mean duration of SWDs, subacute administration (7 days) of IVA decreased the SWDs parameters 24 hours after the 7th injection. Interestingly, when IVA was administered again 24 hours after the 6th IVA injection, it increased the SWDs parameters. Western-blot analyses showed that HCN1 and HCN2 expressions decreased and HCN4 increased in the 5-month-old WAG/Rij rats compared to the 1-month-old WAG/Rij and 5-month-old native Wistar rats, while subacute IVA administration increased the levels of HCN1 and HCN2 channels, except HCN4. Subacute administration of IVA reduced the antiepileptic activity of NNC, while the proepileptic activity of muscimol and the antiepileptic activity of bicuculline were abolished. It might be suggested that subacute IVA administration reduces absence seizures by changing the HCN channel expressions in WAG/Rij rats, and this affects the T-type calcium channels and GABAA receptors.

Poster Session I: Comparison of tripolar and traditional electrodes: Waveform morphology.

The waveforms of visual evoked potentials (VEPs) recorded by tripolar electrodes are different from those recorded by traditional electrode arrays. Traditional arrays record potentials using both an active and a reference electrode. The location of this reference will affect the waveform amplitude and shape. Conversely, tripolar electrodes measure the surface Laplacian across three concentric rings housed within a single electrode surface. These differences may influence the morphology of evoked responses. We compared these two modalities by recording pattern-reversal VEPs to two sizes of checkerboard. Visual inspection of the VEPs suggest that the signals recorded by the tripolar system have attenuated higher frequencies and increased latency of the major waveform components. Root-mean-square comparison of the two signal types confirm attenuation at the higher frequencies in the tripolar recording. Additionally, there is a cumulative delay present within both the large and small check conditions, such that each subsequent component recorded by the tripolar electrodes is shifted increasingly later in time compared to the same components recoded by the traditional electrodes. Such latency shifts may be indicative of a difference in the physiological sources that are measured by the two EEG systems.

Improving the stimulation selectivity in the human cochlea by strategic selection of the current return electrode

The hearing quality provided by cochlear implants is poorly predicted by computer simulations. A high-resolution, human-specific cochlear anatomy is crucial for the accuracy of predictions. In this study, the standard multipolar stimulation paradigms are revisited and Rattay's Activating Function is evaluated in a finite element model of a realistic cochlear geometry that is based on μ-CT images and a commercial lead. The stimulation thresholds across the cochlear fibers were investigated for monopolar, bipolar, tripolar, and a novel (distant) bipolar electrode configuration using an active compartmental nerve model based on Schwartz-Eikhof-Frijns membrane dynamics. The results suggest that jumping of the stimulation point from the vicinity of the cathodic electrode to distant fibers, especially to the low frequency (apical) region of the basilar membrane that is most critical to hearing, occurs more often with monopolar stimulation than other electrode configurations. Bipolar and tripolar electrodes near the apical region did not provide a large threshold margin either. On the other hand, the threshold margin could be improved by proper selection of the electrode for the return current with bipolar stimulation, a technique named here as distant bipolar. The results also demonstrate the significance of having a realistic cochlear geometry in computer models for accurate interpretation for multipolar stimulation paradigms. More selective and focal stimulation may be possible by designing the electrode carrier shape and positioning of the current return electrodes more strategically. This is needed particularly in the apical turn of the cochlea where the current stimulation methods are the least selective.

Differential impact of a ghrelin receptor antagonist or inverse agonist in the electrical kindling model of epilepsy

Ghrelin is a peptide, which has been shown to affect seizures. However, there is not a consensus about its real impact on the control of seizure severity. We assessed the influence of intra-amygdala injections of a ghrelin receptor (GHSR) antagonist, as well as a GHSR inverse agonist on the electrical kindling-induced seizures. Two unipolar electrodes and a tripolar electrode twisted with a guide cannula were implanted in the skull surface or the basolateral amygdala of adult male rats, respectively. A rapid electrical kindling protocol was applied for kindling epileptogenesis. The stimulations were applied until rats showed three consecutive stage five seizures. Each rat was considered as its control. D-Lys-3-GHRP-6 (1, 12.5, and 25 μg/rat) or [D-Arg, D-phe, D-Trp, heu] substance P (D-SP) (50, 500 and 5000 ng/rat) as the GHSR antagonist or inverse agonist were injected into the basolateral amygdala. Seizure parameters including after-discharge duration (ADD), stage five duration (S5D), and seizure stage (SS) were documented thirty minutes following administration of the drugs or saline. Antagonism of the GHSR in the amygdala, significantly increased seizure induction in the kindled rats, in a dose-dependent manner, and induced spontaneous seizures leading to status epilepticus. Conversely, D-SP had a dose-dependent anticonvulsant activity, indicated by decreased ADD and S5D. The results show that GHSR inverse agonism suppressed seizure severity in the rat amygdala kindling model, whereas GHSR antagonism made seizures more severe. Therefore, when considering the ghrelin system to modulate seizures, it is crucial to note the differential impact of various GHSR ligands.

The electrophysiological and behavioral evaluation of the peptide hemopressin and cannabinoid CB1 receptor agonist and antagonist in pentylenetetrazol model of epilepsy in rats.

This study endeavoured to assess the effect of hemopressin (Hp), a nano peptide obtained from the alpha chain of hemoglobin, on chronic epileptic activity and its potential correlation with cannabinoid receptor type 1 (CB1). Male Wistar albino rats (230-260g) were used. The kindling process was conducted by administering a sub-convulsant dose of pentylenetetrazol (PTZ) (35mg/kg, i.p) three times a week for a maximum of 10weeks. Tripolar electrodes and external cannula guides for intracerebroventricular (i.c.v) injections were surgically implanted in the skulls of kindled rats. On the day of the experiment, doses of Hp, AM-251, and ACEA were administered prior to the PTZ injections. Electroencephalography recordings and behavioural observations were conducted simultaneously for 30min after the PTZ injection. The administration of Hp (0.6μg, i.c.v) resulted in a decrease in epileptic activity. The CB1 receptor agonist ACEA (7.5μg, i.c.v) showed an anticonvulsant effect, but the CB1 receptor antagonist AM-251 (0.5μg, i.c.v) displayed a proconvulsant effect. The co-administration of Hp (0.6μg, i.c.v) and ACEA (7.5μg, i.c.v) and of Hp (0.6μg, i.c.v) and AM-251 (0.5μg, i.c.v) produced an anticonvulsant effect. However, when AM-251 was administered prior to Hp, it produced a proconvulsant impact that overrode Hp's intended anticonvulsant effect. Interestingly, the co-administration of Hp (0.03μg) + AM-251 (0.125μg) unexpectedly exhibited an anticonvulsant effect. Electrophysiological and behavioural evaluations demonstrated the anticonvulsant effect of Hp in the present model, highlighting the possibility that Hp may act as an agonist for the CB1 receptor.

PD23-01 EFFECT OF OPIOID RECEPTOR ANTAGONIST ON BLADDER UNDERACTIVITY INDUCED BY PROLONGED PUDENDAL AFFERENT STIMULATION

You have accessJournal of UrologyCME1 Apr 2023PD23-01 EFFECT OF OPIOID RECEPTOR ANTAGONIST ON BLADDER UNDERACTIVITY INDUCED BY PROLONGED PUDENDAL AFFERENT STIMULATION Michael Pintauro, Jianan Jian, Jicheng Wang, Bing Shen, Zhijun Shen, Khari Goosby, Joseph Scolieri, Avanish Madhavaram, Jonathan Beckel, William De Groat, Christopher Chermansky, and Changfeng Tai Michael PintauroMichael Pintauro More articles by this author , Jianan JianJianan Jian More articles by this author , Jicheng WangJicheng Wang More articles by this author , Bing ShenBing Shen More articles by this author , Zhijun ShenZhijun Shen More articles by this author , Khari GoosbyKhari Goosby More articles by this author , Joseph ScolieriJoseph Scolieri More articles by this author , Avanish MadhavaramAvanish Madhavaram More articles by this author , Jonathan BeckelJonathan Beckel More articles by this author , William De GroatWilliam De Groat More articles by this author , Christopher ChermanskyChristopher Chermansky More articles by this author , and Changfeng TaiChangfeng Tai More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003296.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Fowler Syndrome, or non-obstructive urinary retention, is seen in young female patients. Although the cause is unknown, it is theorized that aberrant sensory nerves from the urethral sphincter cause inhibition of the central nervous system, thereby leading to urinary retention. Prior studies have suggested that the opioid receptor may be implicated in bladder overactivity and underactivity. We aimed to evaluate opioid receptor inhibition on bladder function in a feline model of Fowler’s Syndrome. METHODS: A total of 10 cats were anesthetized, ureters externalized via laparotomy, and urethral catheter placed. A tripolar cuff electrode was placed on the pudendal nerve. Multiple cystometrograms (CMGs) were performed to determine baseline bladder function (Control). Multiple pudendal nerve stimulations (PNS) were performed at 30-minute cycles (5 Hz, 0.2 ms) were applied at 4-6 times the intensity required to elicit anal contraction for 2-5 hours. The result was a stable, underactive bladder state (Post-PNS 1). Next, naloxone (1mg/kg IV) was administered, and CMGs obtained (Post-NX). A single 30-minute PNS was then performed to evaluate the combined effect of naloxone and PNS (Post-PNS 2). Lastly, a CMG was performed to examine any recovery (Post-Control). Primary outcomes were bladder capacity and contraction amplitude (contractility). RESULTS: Application of PNS produced a significant increase in bladder capacity and decrease in bladder amplitude, indicative of a state of bladder underactivity (Figure 1, * denotes significance p<0.05). Administration of naloxone significantly reduced the bladder capacity and increased contraction amplitude. Re-application of PNS led fully overcame the naloxone effect on capacity; however, the amplitude is a combined effect. This effect of re-stimulation lasted only for a short period (15-20 minutes) and Post-Control demonstrate a reduction in capacity indicating effects of the still present naloxone overcoming the PNS. CONCLUSIONS: Pharmacologic opioid receptor antagonism increased bladder contractility and reduced bladder capacity to baseline in our feline model of non-obstructive urinary retention. This is a new target for possible pharmacotherapy in the treatment of patients with Fowler's Syndrome. Source of Funding: 5R01DK121698-02 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e670 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Michael Pintauro More articles by this author Jianan Jian More articles by this author Jicheng Wang More articles by this author Bing Shen More articles by this author Zhijun Shen More articles by this author Khari Goosby More articles by this author Joseph Scolieri More articles by this author Avanish Madhavaram More articles by this author Jonathan Beckel More articles by this author William De Groat More articles by this author Christopher Chermansky More articles by this author Changfeng Tai More articles by this author Expand All Advertisement PDF downloadLoading ...

The effect of quercetin on absence epilepsy in WAG/Rij rats

ABSTRACT Aim In the present study, the effect of quercetin, a powerful antioxidant flavonoid, on genetic absence epilepsy was studied in WAG/Rij rats. Material and Method Tripolar electrodes were implanted into WAG/Rij rats. Basal electrocorticography (ECoG) was recorded following a recovery period. After basal ECoG recording, different doses of quercetin (QRC) (25, 50 and 100 mg/kg) were injected intraperitoneally (i.p.) for 30 days. ECoG recording was continued for 31 days, three hours a day. After recording, the rats were anesthetized and euthanized through cervical dislocation and their brains were excised. Biochemically, TNF-alpha, IL-6 and NO were studied in whole rat brains. Results In WAG/Rij rats, low-dose quercetin (25 mg/kg) reduced the number and duration of spike-wave discharges (SWDs) compared to the control group. However, 50 and 100 mg/kg quercetin doses increased SWDs. Duration of SWDs was prolonged only with 100 mg/kg dose. None of the quercetin doses had any effect on average amplitude of SWDs. In addition, it was observed in biochemical analyses that 25 mg/kg quercetin reduced TNF-alpha, IL-6 and NO levels compared to the control group. While TNF-alpha and IL-6 levels in rat brains were not affected by 50 or 100 mg/kg doses, both doses were found to increase NO levels in rat brains. Conclusion Based on the results of the present study, 25 mg/kg low-dose quercetin may have reduced absence seizures by reducing proinflammatory cytokines and NO, but high-dose quercetin may have increased absence seizures through increasing the NO level. This contrasting effect of quercetin on absence seizures needs to be investigated by advanced mechanisms.

Topological specificity of VEP responses: a comparison of tripolar and traditional electrodes

Topological specificity of VEP responses: a comparison of tripolar and traditional electrodes

Effect of low frequency stimulation of olfactory bulb on seizure severity, learning, and memory in kindled rats

Low frequency deep brain electrical stimulation (LFS) is a potential therapeutic strategy to control seizures in epilepsy patients. Given the functional connection of the olfactory bulb with the hippocampal formation, in this study the effect of applying LFS in the olfactory bulb on seizure severity, and learning and memory was investigated in hippocampal kindling. In male Wistar rats (250–300 g), a tripolar electrode was inserted in the CA1 region of the right hippocampus to apply kindling stimulations and record the afterdischarges (ADs). Two bipolar electrodes were also inserted bilaterally into the olfactory bulbs for applying LFS. In the kindled group, the animals received daily kindling stimulations to produce stage 5 seizures for three consecutive days. In one group of subjects, LFS was administered 2–3 min after the last kindling stimulation. Within this group, subjects were divided into two subgroups: one subgroup received two and the other subgroup received four packages of LFS protocol. Obtained data showed that bilateral LFS application to the left and right olfactory bulb reduced seizure severity. Among the protocols, applying four packages of LFS had a greater anticonvulsant effect compared to applying two packages LFS. Applying LFS in the olfactory bulb of kindled subject restored performance on measures that test short- and long-term memory – the Y maze and Morris water maze test – and applying four packages of LFS was more effective than two. These results indicated that applying LFS to the olfactory bulb had anticonvulsant effects and ameliorated the seizure-induced impairment of working and spatial memory. These effects appear to be depended on the number of applied LFS and were greater by increasing the number of LFS.

Acupuncture-Induced Changes in Nociception, Measured by Pain-Related Evoked Potentials: A Pilot Mechanistic Study.

Objective: The nociceptive system has been implicated in acupuncture analgesia, although acupuncture's precise mechanism of action remains unknown. Electric pain-related evoked potentials (PREPs) have emerged as an effective and reliable electrophysiologic method for evaluation of the human nociceptive system by electric stimulation of nociceptive Aδ and C fibers. This pilot mechanistic study aims to assess the feasibility of using advanced PREP techniques together with electroacupuncture and to use PREPs to characterize acupuncture's effect on nociception. Methods: Seven healthy volunteers underwent a previously designed electroacupuncture protocol using acupoints in the legs bilaterally, which has been demonstrated to induce systemic analgesia. Advanced PREP techniques involving tripolar stimulating electrode, varying interstimulus interval, and incorporating a cognitive task during PREPs were used. PREPs were assessed before electroacupuncture, during electroacupuncture, and 30 min after electroacupuncture. Subjective pain perception in response to the PREP-related electric pain stimuli delivered to the nondominant hand was assessed on the visual analog scale (VAS) at baseline, during electroacupuncture, and 30 min postelectroacupuncture. Results: Reliable PREP N1, P1, and N2 waves were obtained from all subjects at the following average latencies: N1 = 131.5 msec, P1 = 189.4 msec, and N2 = 231.1 msec. Electroacupuncture caused a significant reduction in PREP N1P1 wave amplitudes from 25.6 to 15.4 μV (p = 0.006) and electric pain perception on the VAS-from 2.86 to 2.14 (p = 0.008), compared to baseline. These effects were sustained at 30 min postacupuncture with N1P1 wave amplitude 17.2 μV (p = 0.030) and VAS 2.28 (p = 0.030), compared to baseline. Conclusions: Electroacupuncture causes significant changes in objective nociception, measured by PREP N1P1 wave amplitudes, and in subjective nociception, measured by the VAS, and these effects are sustained for 30 min after electroacupuncture. Planned future studies will involve chronic pain populations and will aim to assess acupuncture's longer term analgesic effects.

THE effect of general anesthetics on genetic absence epilepsy in WAG/Rij rats

ABSTRACT Aim To establish safe and straightforward anesthesia used in experiments, we examined the effect of ketamine, ketamine/xylazine, urethane, chloral hydrate, pentobarbital, isoflurane, dexmedetomidine, and dexmedetomidine/ketamine on epileptiform activity in genetic absence epilepsy (WAG\\Rij) rats. Materials and Method Sixty-three male WAG/Rij rats weighing (170–190 g) were used. Tripolar electrodes were inserted into the skull. After ECoG activities were recorded for each animal for 2 hours as controls, , the anesthetic substances were administered and the recording continued for another 2 hours. All the anesthetic substances were administered intraperitoneally except isoflurane, which was administered by inhalation.The PowerLab system was used for electrophysiological activity recording and analysis. Results The administration of ketamine (90 mg/kg), ketamine/xylazine (90/10 mg/kg), urethane (1.25 g/kg), chloral hydrate (175 mg/kg), pentobarbital (50–90 mg/kg), isoflurane (induction 5%, maintaining 3–4%), dexmedetomidine (0.5–1 mg/kg), and dexmedetomidine/ketamine (50/90 mg/kg), significantly decreased the total number of SWD, the total number of spikes, and the SWD duration (p < 0,05). The mean duration of SWD was not affected in pentobarbital (50–90 mg/kg), isoflurane (induction 5%, maintaining 3–4%), dexmedetomidine (0.5–1 mg/kg), and Dexmedetomidine/ketamine (50/90 mg/kg) groups (p > 0.05). Time scale showed a significant decrease in the total number of SWD in the first 20 minutes (P < 0.001) for all groups except dexmedetomidine (0.5–1 mg/kg), and dexmedetomidine/ketamine (50/90 mg/kg) groups (p > 0.05). Conclusion The anesthetics we used significantly reduced the epileptiform activity immediately after the administration, except dexmedetomidine and dexmedetomidine/ketamine groups, so we recommend using dexmedetomidine and Dexmedetomidine/ketamine in electrophysiological studies accompanied by anesthetics.

In vivo peripheral nerve activation using sinusoidal low-frequency alternating currents.

The sinusoidal low-frequency alternating current (LFAC) waveform was explored recently as a novel means to evoke nerve conduction block. In the present work, we explored whether increasing the amplitude of the LFAC waveform results in nerve fiber activation in autonomic nerves. In-silico methods and preliminary work in somatic nerves indicated a potential frequency dependency on the threshold of activation. The Hering-Breuer (HB) reflex was used as a biomarker to detect cervical vagus nerve activation. Experiments were conducted in isoflurane-anesthetized swine (n=5). Two stimulating bipolar cuff electrodes and a tripolar recording cuff electrode were implanted on the left vagus nerve. To ensure the electrical stimulation affects only the afferent pathways, the nerve was crushed caudal to the electrodes to eliminate cardiac effects. (1) Standard pulse stimulation (Vstim) using a monophasic train of pulses was applied through the caudal electrode to elicit HB reflex and to identify the activated nerve fiber type. (2) Continuous sinusoidal LFAC waveform with a frequency ranging from 5 through 20 Hz was applied to the rostral electrode without Vstim to explore the activation thresholds at each LFAC frequency. In both cases, the activation of nerve fibers was detected by a HB reflex-induced reduction in the breathing rate. LFAC was found to be capable of eliciting an HB response. The LFAC activation thresholds were found to be frequency-dependent. The HB threshold was 1.02 ± 0.3 mAp at 5Hz, 0.66 ± 0.3 mAp at 10Hz, and 0.44 ± 0.2 mAp at 20 Hz. In comparison, it was 0.7 ± 0.47 mA for a 100 μs pulse. The LFAC amplitude was within the linear limits of the electrode interface. Damage to the cuff electrodes or the nerve tissues was not observed. Analysis of Vstim-based compound nerve action potentials (CNAP) indicated that the decrease in breathing rate was found to be correlated with the activation of slower components of the CNAP suggesting that LFAC reached and elicited responses from these slower fibers associated with afferents projecting to the HB response. These results suggest the feasibility of the LFAC waveform at 5, 10, and 20 Hz to activate autonomic nerve fibers and potentially provide a new modality to the neurorehabilitation field.

Non-invasive auditory brainstem responses to FM sweeps in awake big brown bats

We introduce two EEG techniques, one based on conventional monopolar electrodes and one based on a novel tripolar electrode, to record for the first time auditory brainstem responses (ABRs) from the scalp of unanesthetized, unrestrained big brown bats. Stimuli were frequency-modulated (FM) sweeps varying in sweep direction, sweep duration, and harmonic structure. As expected from previous invasive ABR recordings, upward-sweeping FM signals evoked larger amplitude responses (peak-to-trough amplitude in the latency range of 3–5 ms post-stimulus onset) than downward-sweeping FM signals. Scalp-recorded responses displayed amplitude-latency trading effects as expected from invasive recordings. These two findings validate the reliability of our noninvasive recording techniques. The feasibility of recording noninvasively in unanesthetized, unrestrained bats will energize future research uncovering electrophysiological signatures of perceptual and cognitive processing of biosonar signals in these animals, and allows for better comparison with ABR data from echolocating cetaceans, where invasive experiments are heavily restricted.

Anticonvulsant activity of the histamine H3 receptor inverse agonist pitolisant in an electrical kindling model of epilepsy

Studies have shown that brain histamine has a role in seizure pathophysiology. Histamine acts by four distinct receptor subtypes (H1R–H4R). Previous reports signified the anticonvulsant activity of histamine H3R antagonists. We evaluated the effect of intra-amygdala injection of pitolisant the H3R inverse agonist on seizures induced by the electrical kindling model of epilepsy. Eighteen adult male rats with an approximate weight of 300 g were used. A tri-polar electrode twisted with the guide cannula, and two monopolar electrodes were implanted into the basolateral amygdala or the surface of the skull using stereotaxic surgery. One week after surgery, the threshold was determined in the animals. Twenty-four hours afterward, the animals received six stimuli daily with the threshold intensity until the generation of three consecutive stages five seizures. Then, saline, and 24 h later, pitolisant at three doses (1, 10, and 100 μg) were injected into the amygdala in distinct rats. Thirty minutes after injection of the drug or its solvent, seizure parameters including after-discharge duration (ADD), seizure stage (SS), and stage five duration (S5D) were recorded. Data analysis indicated that pitolisant reduced S5D at all doses, significantly. Pitolisant at the dose of 100 µg also decreased ADD and SS, significantly. However, pitolisant at the doses of 1 and 10 µg did not change ADD and SS. The dose–response curves showed that the anticonvulsant activity of pitolisant changed in a dose-dependent manner. In conclusion, the results confirmed the powerful anticonvulsant effects of pitolisant in the electrical kindling model of epilepsy.

Electrophysiological, histopathological, and biochemical evaluation of the protective effect of probiotic supplementation against pentylenetetrazole-induced seizures in rats.

Research on the relationship between the gut microbiome and epilepsy is accumulating. The present study was conducted to evaluate the effect of probiotic supplementation on pentylenetetrazole (PTZ)-induced seizures in rats. Twenty-one adult male Wistar albino rats were included. The animals were divided into three groups of seven rats. Group 1 was a control group, whereas Group 2 rats received PTZ treatment and Group 3 rats had PTZ+PB (probiotic) treatment. For 6weeks, Groups 1 and 2 were given saline (1ml), whereas Group 3had probiotic supplement. In the 5th week, tripolar electrodes were attached to the rats. Electrophysiological, behavioral, biochemical, and immunohistochemical evaluations were performed in the 6weeks after the treatment. PB treatment significantly reduced seizures. In the PTZ group, expression levels of brain-derived neurotrophic factor, nerve growth factor (NGF), and Sox2 (SRY sex-determining region Y-box 2) in rat brains decreased significantly compared to the control group, whereas the expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), total oxidant status (TOS), and nitric oxide (NO) levels increased. In the PTZ+PB group, NGF expression increased significantly compared to the PTZ group, whereas TNF-α, IL-6, TOS, and NO levels decreased. In histopathological examination, an abundance of necrotic neurons was notable in the PTZ group, which was less in the PTZ+PB group. In addition, body weight of the group supplemented with probiotics decreased after the treatment. Our results suggest that probiotic supplementation may alleviate seizure severity and exert neuroprotective effects by reducing neuroinflammation and oxidative stress and altering the expression of neurotrophins in epileptogenic brains.

Tripolar Electrode Electrochemical Impedance Spectroscopy for Endoscopic Devices toward Early Colorectal Tumor Detection.

Embedded sensors for endoscopy devices have been studied toward a convenient and decision-supportive methodology in colorectal cancer (CRC) diagnosis, but no device could provide direct CRC screening with in situ measurements. In this study, we proposed a millimeter-scale electrical impedance spectroscopy (EIS) device that can be integrated into a biopsy tool in endoscopy for colorectal tumor detection. A minimally invasive tripolar electrode was designed to sense the tissue impedance, and a multilayer neural network was implemented for the classification algorithm. The sensor performance was investigated in terms of sensitivity, reliability, and repeatability using dummy tissues made of agarose hydrogels at various saline concentrations. In addition, an in vivo study was conducted in mice with an implanted CT-26 colon tumor line. The results demonstrated that the prototyped EIS device and algorithm can detect the tumor tissue in suspicious lesions with high sensitivity and specificity of 87.2 and 92.5%, respectively, and a low error of 7.1%. The findings of this study are promising for in situ CRC screening and may advance the diagnostic efficacy of CRC detection during endoscopic procedures.

Temperature Effect on Nerve Conduction Block Induced by High-Frequency (kHz) Biphasic Stimulation

ObjectivesThis study aims to determine temperature effect on nerve conduction block induced by high-frequency (kHz) biphasic stimulation (HFBS). Materials and MethodsFrog sciatic nerve-muscle preparation was immersed in Ringer’s solution at a temperature of 15 or 20 °C. To induce muscle contractions, a bipolar cuff electrode delivered low-frequency (0.25 Hz) stimulation to the nerve. To induce nerve block, a tripolar cuff electrode was placed distal to the bipolar cuff electrode to deliver HFBS (2 or 10 kHz). A bipolar hook electrode distal to the blocking electrode was used to confirm that the nerve block occurred locally at the site of HFBS. A thread tied onto the foot was attached to a force transducer to measure the muscle contraction force. ResultsAt 15 °C, both 2- and 10-kHz HFBSs elicited an initial transient muscle contraction and then produced nerve block during the stimulation (ie, acute block), with the 10 kHz having a significantly (p < 0.001) higher acute block threshold (5.9 ± 0.8 mA peak amplitude) than the 2 kHz (1.9 ± 0.3 mA). When the temperature was increased to 20 °C, the acute block threshold for the 10-kHz HFBS was significantly (p < 0.0001) decreased from 5.2 ± 0.3 to 4.4 ± 0.2 mA, whereas the 2-kHz HFBS induced a tonic muscle contraction during the stimulation but elicited nerve block after terminating the 2-kHz HFBS (ie, poststimulation block) with an increased block duration at a higher stimulation intensity. ConclusionTemperature has an important influence on HFBS-induced nerve block. The blocking mechanisms underlying acute and poststimulation nerve blocks are likely to be very different.

Antagonism of the ghrelin receptor type 1a in the rat brain induces status epilepticus in an electrical kindling model of epilepsy.

Studies have shown the anti-seizure properties of the ghrelin hormone in different models of epilepsy. Nevertheless, the role of the endogenous ghrelin is unknown in the electrical kindling model of epilepsy. In this study, we evaluated the effect of the antagonism of the ghrelin receptors in the brain of fully kindled rats. Adult male Wistar rats weighing 300g were used. Animals were stereotaxically implanted with two uni-polar electrodes in the skull surface and a tri-polar electrode in the basolateral amygdala, and a guide cannula in the left lateral ventricle. Animals underwent a rapid kindling protocol. After showing three consecutive stages of five seizures, the animals were considered fully kindled. D-Lys-3-GHRP-6 (1, 50, and 100μg/rat) was injected intracerebroventricularly (i.c.v.) in the kindled animals. Each rat was considered as its control and received a single dose of D-Lys-3-GHRP-6. Seizure parameters including after discharge duration (ADD), seizure stage (SS), stage four latency (S4L), and stage five duration (S5D) were recorded. The paired t test indicated a significant increase in seizure induction. D-Lys-3-GHRP-6 (1μg/rat; i.c.v.) prolonged ADD in the kindled rats, significantly. D-Lys-3-GHRP-6 (50 and 100μg/rat; i.c.v.) induced spontaneous seizures, which led to status epilepticus in the kindled rats. The results indicate that the antagonism of the ghrelin functional receptors prolongs seizures and induces status epilepticus in the kindling model of epilepsy, and propose that the endogenous ghrelin signaling has crucial antiepileptic properties.