Inhibition Of Motor Activity Research Articles

Doxorubicin Effects on Cognitive Impairment and the Microscopic View of Brain Structures in Rats

The creation of a validated model of the “chemical brain” in laboratory animals is an urgent task, the solution of which will optimize the search for new drugs for the prevention and pharmacological correction of delayed effects of chemotherapy on the central nervous system. The aim of the work has been to assess the effect of doxorubicin after systemic course administration on behavioral reactions and the microscopic view of the cerebral cortex and hippocampus in rats.Doxorubicin was administered intraperitoneally to male rats at doses of 5 and 6 mg/kg, once a week, for 28 days. The behavioral reactions of the animals were assessed, and pathomorphological studies of the cerebral cortex and hippocampus were carried out.Doxorubicin at doses of 5 and 6 mg/kg causes inhibition of motor activity in the “Open Field” test, impairment of non-spatial and spatial memory in the “New Object Recognition” and “Y-Maze” tests, respectively. Doxorubicin at these doses increases the severity of vascular congestion and perivascular edema in the cerebral cortex and hippocampus.Doxorubicin at doses of 5 and 6 mg/kg causes impairment of cognitive functions in rats in tests assessing non-spatial and spatial memory, as well as microcirculation disorders in the cerebral cortex and hippocampus of rats.

Analysis of correlations between behavioral parameters in the elevated plus maze and the levels of interleukin-1beta in blood plasma in rats

Peripheral cytokines may influence psychoemotional behavior, but the role of interleukin-1beta (IL-1beta) in altering anxiety and motor activity in response to inflammatory activation remains unclear. To clarify this issue, correlations between behavioral parameters in the elevated plus maze (EPM) test and plasma levels of IL-1beta after administration of the proinflammatory stimulus lipopolysaccharide (LPS) in different modes were analyzed in adult male rats. LPS in doses of 0.5 or 5 mg/kg, as well as physiological solution (control), were administered to rats intraperitoneally. The most pronounced behavioral effect 24 hours after a single injection was an endotoxin dose-dependent inhibition of the animals’ motor activity. After a dose of 5 mg/kg, increased anxious behavior was also noted every other day. The behavioral changes caused by the high dose of endotoxin were completely normalized after a week. The behavior of the animals one day after the end of repeated injections of LPS at a lower dose for a week (0.5 mg/kg; once every two days) also did not differ from the control. The inhibition of motor activity after LPS could be due to an increase in the level of IL-1beta in the blood plasma, as indicated by the identified significant negative correlations between IL-1beta and the corresponding behavioral parameters. No significant correlation was found between the peripheral level of IL-1beta and such a classic indicator of anxiety as the percentage of entries into the open arms of the maze. In general, the obtained results allow us to conclude that IL-1beta is an undoubted participant in the mechanism of the transient inhibitory effect of LPS on motor activity.

Case Report and Literature review. Neuropsychiatry Manifestation of Frontal Lobe Neoplasm- Meningioma. Prevalence, Presentation and Pathogenesis

IntroductionMeningiomas are the most frequent primary brain tumor. Although most Meningiomas are benign, their location in the central nervous system can predict symptomatology which could result in significant morbidity and mortality. However, due to the slow-growing nature, meningiomas are usually asymptomatic, and diagnosis is often made incidentally on neuroimaging or at an autopsy. The incidence rate is 1.2-fold higher in Black Americans than White Americans. Neuropsychiatry manifestation might be only initial presentation; thus, psychiatrists are often the first to see these patients, and the correct diagnosis may be made only when the tumor has grown to a considerable size and begun to displace the brain.ObjectivesThe aim of this study is to understand the biological basis of psychiatry symptoms in patients with Frontal Lobe meningiomas.MethodsA review of literature and individual patient data analysis was conducted. The literature review was conducted on PubMed, Medline, MeSH, Google Scholar, and mount Sinai’s levy Library using the key words; meningioma, meningioma with psychiatric symptoms, psychosis, depression, neuropsychiatry manifestation of meningiomas.ResultsThe review revealed that 88% of brain tumors and psychiatric symptoms are located in the frontal region. Meningiomas accounts for 13%-26% of intracranial tumors. There is a reported low incidence due to its slow growing nature and are usually asymptomatic. Incidence of meningiomas is predominant in females, and is attributed to hormonal factors, this is associated with estrogen and progestogen cycles. Reports shows that smoking has been linked to increase risk of meningiomas in men. Frontal lobe meningiomas may present with only psychological symptoms that resemble depression, anxiety states, hypomania and schizophrenia. Personality and mental status changes are also noted in Frontal lobe tumors. Left sided lesions are associated with inhibition of motor activity, impairment in motor and initiative aspect of speech, diminished generalization ability and general inertia of mental process.Conclusions Given the absence of frank neurological symptoms, to help localize the lesion, most meningiomas are missed due to diagnostic overshadowing of the primary psychiatric illness. Peritumoral edema indicates the underlying mechanism and location of the lesion predicts symptomatology. Like our patient who is an 81-year-old male with no past psychiatry history, presenting to our comprehensive psychiatry emergency program with psychiatric manifestation as the initial presentation and subsequently with MRI suggestive of Right Frontal extra-axial meningioma. This study shows that primitive frontal lobe tumors are likely to be misdiagnosed as patients with such tumors are often referred first to psychiatrist. High index of suspicious is needed.Disclosure of InterestNone Declared

Mechanism of small molecule inhibition of Plasmodium falciparum myosin A informs antimalarial drug design

Malaria results in more than 500,000 deaths per year and the causative Plasmodium parasites continue to develop resistance to all known agents, including different antimalarial combinations. The class XIV myosin motor PfMyoA is part of a core macromolecular complex called the glideosome, essential for Plasmodium parasite mobility and therefore an attractive drug target. Here, we characterize the interaction of a small molecule (KNX-002) with PfMyoA. KNX-002 inhibits PfMyoA ATPase activity in vitro and blocks asexual blood stage growth of merozoites, one of three motile Plasmodium life-cycle stages. Combining biochemical assays and X-ray crystallography, we demonstrate that KNX-002 inhibits PfMyoA using a previously undescribed binding mode, sequestering it in a post-rigor state detached from actin. KNX-002 binding prevents efficient ATP hydrolysis and priming of the lever arm, thus inhibiting motor activity. This small-molecule inhibitor of PfMyoA paves the way for the development of alternative antimalarial treatments.

Phrenic-to-intercostal reflex activity in response to high frequency spinal cord stimulation (HF-SCS)

ObjectiveHF-SCS is a novel technique of inspiratory muscle activation which results in coincident activation of the diaphragm and inspiratory intercostal muscles via spinal cord pathways and has the potential to provide respiratory support in ventilator dependent persons with spinal cord injury. The purpose of the present study was to examine the phrenic-to-intercostal reflex during HF-SCS. MethodsIn 5 anesthetized and C2 spinalized dogs, electrical stimulation was applied via a stimulating electrode located on the ventral surface of the upper thoracic spinal cord at the T2 level. Fine wire recording electrodes were used to assess single motor unit (SMU) activity of the left and right external intercostal muscles (EI) in the 3rd interspace before and after sequential left and right phrenicotomy. ResultsMean control peak firing frequency of the right EI and left EI was 11.4 ± 0.3 Hz and 10.6 ± 0.3 Hz respectively. Following unilateral right phrenic nerve section, mean SMU peak firing frequency of right EI (ipsilateral to the section) was significantly greater when compared to control (15.9 ± 0.5 Hz vs 11.4 ± 0.3 Hz; p = 0.01). Mean SMU peak firing frequency of the contralateral left EI remained unchanged (10.2 ± 0.3 Hz vs 10.6 ± 0.3 Hz, p = 0.40). Subsequent, section of the left phrenic nerve resulted in significantly higher mean SMU peak firing frequency of the left EI (16.2 ± 0.5 Hz vs 10.2 ± 0.3 Hz) when compared to before section p = 0.01). Contralateral, right EI peak firing frequency was not different if compared to before left phrenic nerve section (16.9 ± 0.4 Hz vs. 15.9 ± 0.5 Hz; p = 0.14). ConclusionThis study demonstrates that during HF-SCS: 1) unilateral diaphragmatic afferents reflexly inhibit motor activity to the ipsilateral EI muscles, 2) the neural circuitry mediating the phrenic-to-intercostal reflex is preserved at a spinal level and does not require supraspinal input and 3) unilateral compensatory increases were observed in EI muscle activation following ipsilateral diaphragm paralysis.

De novo mutations in KIF1A-associated neuronal disorder (KAND) dominant-negatively inhibit motor activity and axonal transport of synaptic vesicle precursors

KIF1A is a kinesin superfamily motor protein that transports synaptic vesicle precursors in axons. Cargo binding stimulates the dimerization of KIF1A molecules to induce processive movement along microtubules. Mutations in human Kif1a lead to a group of neurodegenerative diseases called KIF1A-associated neuronal disorder (KAND). KAND mutations are mostly de novo and autosomal dominant; however, it is unknown if the function of wild-type KIF1A motors is inhibited by heterodimerization with mutated KIF1A. Here, we have established Caenorhabditis elegans models for KAND using CRISPR-Cas9 technology and analyzed the effects of human KIF1A mutation on axonal transport. In our C. elegans models, both heterozygotes and homozygotes exhibited reduced axonal transport. Suppressor screening using the disease model identified a mutation that recovers the motor activity of mutated human KIF1A. In addition, we developed invitro assays to analyze the motility of heterodimeric motors composed of wild-type and mutant KIF1A. We find that mutant KIF1A significantly impaired the motility of heterodimeric motors. Our data provide insight into the molecular mechanism underlying the dominant nature of de novo KAND mutations.

Shulin packages axonemal outer dynein arms for ciliary targeting.

The main force generators in eukaryotic cilia and flagella are axonemal outer dynein arms (ODAs). During ciliogenesis, these ~1.8-megadalton complexes are assembled in the cytoplasm and targeted to cilia by an unknown mechanism. Here, we used the ciliate Tetrahymena to identify two factors (Q22YU3 and Q22MS1) that bind ODAs in the cytoplasm and are required for ODA delivery to cilia. Q22YU3, which we named Shulin, locked the ODA motor domains into a closed conformation and inhibited motor activity. Cryo-electron microscopy revealed how Shulin stabilized this compact form of ODAs by binding to the dynein tails. Our findings provide a molecular explanation for how newly assembled dyneins are packaged for delivery to the cilia.

Neurocircuit differences between memory traces of persistent hypoactivity and freezing following fear conditioning among the amygdala, hippocampus, and prefrontal cortex.

We aimed to investigate the persistent trace of one traumatic event on neurocircuit controls in rats. Conditioning was reflected by reductions in rates of ‘freezing’ and ‘other-than-freezing’ motor activities, between which rats could alternate on delivery of pulsed footshocks of intensity 0.5 mA but not 1.0 mA. At the latter intensity, freezing began to suppress motor activity. The conditional responses evident during both the context and tone sessions persisted when the tests were repeated on post-conditioning days 7 and 8. Thus, difficulties with fear extinction/reduction remained. However, persistence was not evident on post-conditioning days 1 and 2. One day after the 1.0 mA pulsed footshock, ibotenate lesions and corresponding sham surgeries were performed in unilateral and bilateral hemispheres of the amygdala, hippocampus, and prefrontal cortex, as well as three different disconnections (one unilateral and another contralateral lesions out of three regions, a total of nine groups), and were tested on days 7–8. The drastic restoration of freezing following bilateral amygdala lesions was also evident in animals with three types of disconnection; however, this was not the case for hypoactivity. These results imply that a serious experience can drive different neurocircuits that all involve the amygdala, forming persistent concurrent memories of explicit (e.g., ‘freezing’) or implicit (e.g., ‘other-than-freezing’ motor activity) emotions, which may exhibit mutual interference.

Substantia nigra pars reticulata-mediated sleep and motor activity regulation.

The substantia nigra pars reticulata (SNR) is a major output nucleus of the basal ganglia. Animal studies have shown that lesions of the SNR cause hyposomnia and motor hyperactivity, indicating that the SNR may play a role in the control of sleep and motor activity. Eight 8- to 10-week-old adult male Sprague-Dawley rats were used. After 3 days of baseline polysomnographic recording, dialysates were collected from the lateral SNR across natural sleep-wake states. Muscimol and bicuculline were microinfused into the lateral SNR. We found that GABA release in the lateral SNR is negatively correlated with slow wave sleep (SWS; R = -0.266, p < 0.01, n = 240) and positively correlated with waking (R = 0.265, p < 0.01, n = 240) in rats. Microinfusion of muscimol into the lateral SNR decreased sleep time and sleep quality, as well as eliciting motor hyperactivity in wake and increased periodic leg movement in SWS, while bicuculline infused into the lateral SNR increased sleep and decreased motor activity in SWS in rats. Muscimol infusion skewed the distribution of inter-movement intervals, with most between 10 and 20 s, while a flat distribution of intervals between 10 and 90 s was seen in baseline conditions. Activation of the lateral SNR is important for inducing sleep and inhibiting motor activity prior to and during sleep, and thus to the maintenance of sleep. Abnormal function of the lateral SNR may cause hyposomnia and motor hyperactivity in quiet wake and in sleep.

Dehydroepiandrosterone increases tonic and phasic dopamine release in the striatum

Dehydroepiandrosterone (DHEA) modulates dopaminergic neurotransmission. It takes part in neurologic and psychiatric diseases involving monoamine neurotransmitters. Earlier results show that DHEA (120-min treatment) reduced striatal dopamine (DA) turnover in rats, suggesting a reduced DA release. Some investigations report that DHEA increases DA release but inhibits motor activity, which seems contradictory. This research examines the effect of DHEA on striatal DA release, its metabolism and motor activity. Male Wistar rats were implanted in the striatum with a cannula for in vivo microdialysis. DHEA was administered (120 mg/kg) and dialysates were collected for 280 min. A depolarizing stimulus was applied at 120 min. Samples were analyzed by HPLC-ED to determine the concentration of DA and its metabolites. The effect of DHEA on motor activity was also evaluated during 120 min. Extracellular DA concentration was greater in treated animals both before and after depolarization. In contrast, DHEA reduced the areas below the curves for DA metabolites and DA/metabolite ratios. DHEA also reduced motor activity, remarkably in the first 20 min after treatment. In summary, DHEA yielded a stimulatory effect on striatal DA release that was not reflected in neither DA metabolism nor motor activity. Thus, DHEA resembles the effect of typical antipsychotics, increasing DA release but reducing behavioral activation.

TRPA1 Channel Activation Inhibits Motor Activity in the Mouse Colon

There is a growing awareness of the role that TRP channels play in regulating sensory and motor functions in the gastrointestinal tract. In this study we used an in-vitro murine model of colonic peristaltic-like complexes (CPMCs) to evaluate the role of exogenous and endogenous TRPA1 signaling processes in regulating colonic motility. Using in-vitro recordings of intraluminal pressure to monitor the presence of CPMCs in colonic segments we performed a series of experiments on male CD1 mice (2 months of age) and found that CPMC activity was attenuated by TRPA1 agonists. Bath application of the TRPA1 antagonist HC-030031 had no effect upon basal CPMC activity whereas application of the synthetic TRPA1 agonist ASP7663 caused a reversible dose dependent decrease in CPMC frequency that was blocked by HC-030031. Cinnamaldehyde and 4-hydroxy-2-nonenal elicited long lasting decreases in CPMC frequency that were blocked by HC-030031 whereas the decreased CPMC activity invoked by AITC could not be blocked by HC-030031. Our results show that any potential mechanosensory function of TRPA1 doesn’t involve contributing to distension induced colonic motor activity and that a role for TRPA1 in the colon is through regulating motility through exogenous and endogenous agonist induced inhibitory effects.

Neurobiology: Swimming at the Intersection of Light and Gravity.

Many animals use gravity as a spatial reference to help navigate their surroundings, but how they do so is not well understood. A new study reveals that a representative of our closest invertebrate relatives, the tunicate Ciona, processes light and gravity cues through a simple neural circuit to decide when and how to swim.

Analgesic, anti-inflammatory, and central nervous system depressant activities of Monochoria hastate (L.) Solms. in animal models

Background: Monochoria hastate (L.) Solms. is extensively used as traditional medicine despite the fact that no scientific data has yet been published revealing its biological activity in vivo. Objectives: The objective of the study was to investigate the pharmacological effect of crude leaf extracts of M. hastate in mice model, justifying its medicinal use and evaluating its safety and efficacy as a crude drug. Materials and Methods: Crude extracts were prepared using methanol and ethyl acetate as solvent. Analgesic activity was evaluated by writhing and formalin-induced licking bioassay. Anti-inflammatory activity was examined by detecting its effect on carrageenan-induced edema. Effect on the central nervous system (CNS) was tested by monitoring movements of test animals by open-field and hole-cross assay. Results: Oral administration (400 mg/kg) of methanol and ethyl acetate extract resulted in 93% and 92% reduction of writhing (P < 0.001) compared to the 87% by diclofenac, whereas ethyl acetate extract caused maximum inhibition (91%) of licking response. Both the extracts manifested marked (P < 0.05) reduction in edema diameter, but the effects were less significant than the standard. Open-field and hole-cross test demonstrated significant (P < 0.001) suppression of motor activity in the treated group. The resulting movements 120 min after oral administration of methanol and ethyl acetate extract (400 mg/kg) and diazepam (1 mg/kg) were 205.8 ± 33, 1.4 ± 0.5, 217 ± 28, 1.0 ± 0.3, 191.2 ± 25, and 2.0 ± 0.7, respectively. Conclusion: These findings provide substantial evidence that leaf extracts of M. hastate possess analgesic, anti-inflammatory, and CNS depressant activity in mice explaining some of its use in traditional medicine.

The study of neurotoxicity of toluene in conditions of experimental modeling of prenatal hypoxic damage of the brain

There was executed the study of the impact of toluene on indices of behavior, cognitive capabilities and bioelectric activity of the brain in white rats with normal course of the period of antenatal development and against background ofprenatal hemic hypoxia Prenatal hypoxia was modeled in pregnant female rats by subcutaneous injection of sodium nitrite in a dose of 50 mg/kg at from the 10 to the 19 day of gestation. At the age of 3 months the males from the obtained offspring were exposed to inhalation exposure of toluene (150 ppm, 4 weeks). After exposure to toluene in animals there was evaluated the pattern of individual behavior, indices of cognitive capabilities and also bioelectric activity of the brain. There were revealed such common consistencies of transformations in the behavior of exposed to toluene animals with normal and impaired embryogenesis as disturbed motor activity, reduction of exploratory behavior and cognitive functions, impaired bioelectric potentials of the brain. Features of changes in behavior and EEG indices in toluene-exposed rats with prenatal hypoxia are characterized by inhibition of motor activity, increased anxiety and latency of main peaks of auditory and visual evoked potentials. Prenatal hypoxic damage of the central nervous system was shown to be an aggravating factor in toluene intoxication in rats.

Sleep and body temperature in TNFα knockout mice: The effects of sleep deprivation, β3-AR stimulation and exogenous TNFα

Increased production of pro-inflammatory cytokines is assumed to mediate increased sleep under inflammatory conditions, such as systemic infections or recovery from sleep loss. The role of cytokines in sleep regulation under normal conditions is less clear. In the present study, we investigated the role of endogenous tumor necrosis factor alpha (TNFα) in sleep regulation using TNFα knockout (KO) mice. Under control conditions at thermoneutral ambient temperature, total sleep time did not differ between TNFα KO and wild-type (WT) mice, but TNFα KO mice had increased rapid-eye-movement sleep (REMS), accompanied by decreased motor activity and body temperature. Exposure to 17 °C induced decreases in total sleep time similarly in both genotypes. Sleep deprivation by gentle handling elicited robust rebound increases in non-rapid-eye movement sleep (NREMS), REMS and electroencephalographic (EEG) slow-wave activity (SWA), accompanied by suppressed motor activity and decreased body temperature; there was no significant difference between the responses of WT and KO mice. Systemic injection of the beta3-adrenergic receptor (β3-AR) agonist CL-316,243 induced increases in NREMS and body temperature. The temperature response, but not the sleep effect, was attenuated in the KO animals. Systemic injection of TNFα induced increased NREMS, reduced REMS and biphasic temperature responses in both genotypes. In the KO mice, the NREMS-promoting effects of exogenously administered TNFα was decreased, while REMS suppression was enhanced, and the first, hypothermic, phase of temperature response was attenuated. Overall, TNFα KO mice did not show any deficiency in sleep regulation which suggests that the role of endogenous TNFα in sleep regulation is less pronounced than previously suggested.

A Motor Theory of Sleep-Wake Control: Arousal-Action Circuit.

Wakefulness, rapid eye movement (REM) sleep, and non-rapid eye movement (NREM) sleep are characterized by distinct electroencephalogram (EEG), electromyogram (EMG), and autonomic profiles. The circuit mechanism coordinating these changes during sleep-wake transitions remains poorly understood. The past few years have witnessed rapid progress in the identification of REM and NREM sleep neurons, which constitute highly distributed networks spanning the forebrain, midbrain, and hindbrain. Here we propose an arousal-action circuit for sleep-wake control in which wakefulness is supported by separate arousal and action neurons, while REM and NREM sleep neurons are part of the central somatic and autonomic motor circuits. This model is well supported by the currently known sleep and wake neurons. It can also account for the EEG, EMG, and autonomic profiles of wake, REM, and NREM states and several key features of their transitions. The intimate association between the sleep and autonomic/somatic motor control circuits suggests that a primary function of sleep is to suppress motor activity.

Investigating the effect of anticipating a startling acoustic stimulus on preparatory inhibition

Motor-evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) show a profound suppression when elicited during the instructed-delay of reaction time (RT) tasks. One predominant hypothesis is that this phenomenon, called "preparatory inhibition", reflects the operation of processes that suppress motor activity to withhold prepared (but delayed) responses, a form of impulse control. In addition, a startling acoustic stimulus (SAS) -a loud and narrow sound- can trigger the release of prepared responses in RT tasks. We predicted that, if such premature release is clearly forbidden, then anticipating a SAS during delay periods may be associated with increased preparatory inhibition for greater impulse control. Subjects performed a behavioural (n=16) and TMS (n=11) experiment. Both used a choice RT task that required subjects to choose a response based on a preparatory cue but to only release it after an imperative signal. SAS and TMS pulses were elicited at the end of the delay period and subjects were asked to do their best to only release their response after the imperative signal, even in the presence of SAS. SAS could be either rare or frequent, in separate blocks. Consistent with the literature, SAS shortened RTs, especially when they occurred frequently. Moreover, MEPs were suppressed when subjects delayed prepared responses but this preparatory inhibition did not depend on whether SAS were frequent or rare. The stronger RT shortening with frequent rather than rare SAS may be due to increased attention and/or reduced reactive inhibition to SAS, leaving preparatory inhibition unaffected.

The history and progress of local anesthesia: multiple approaches to elongate the action.

Analgesia and temporary inhibition of motor activity without interfering with central nervous function have been the essential merits of local anesthesia. Local anesthetics originated from cocaine have played a major role in local analgesia. However, the relatively short duration of action of local anesthetics has been a concern in intra- and post-operative analgesia. From the early age of modern local anesthesia, physicians and medical scientists had been struggling to control the active duration of local anesthetics. Such approach includes: development of long-acting local anesthetics, with physical tourniquet techniques, co-administration of other medicines such as vaso-constrictive agents or analgesics, development of mechanical devices to continuously or intermittently administer local anesthetics, and utilization of pharmaceutical drug delivery systems. In this review, the historical sequence of studies that have been performed in an effort to elongate the action of local anesthetics is presented, referring to epoch-making medical and scientific studies.

Phrenic‐to‐Intercostal Reflex Activity in Response to High Frequency Spinal Cord Stimulation (HF‐SCS)

ObjectiveHF‐SCS is a novel technique of inspiratory muscle activation which results in coincident activation of the diaphragm and inspiratory intercostal muscles via spinal cord pathways and has the potential to provide respiratory support in ventilator dependent persons with spinal cord injury. The purpose of the present study was to examine the phrenic to intercostal reflex during HF‐SCS.MethodsIn 3 anesthetized and C2 spinalized dogs, electrical stimulation was applied via a stimulating electrode located on the ventral surface of the upper thoracic spinal cord at the T2 level before and after cervical phrenicotomy. Fine wire recording electrodes were used to assess single motor unit (SMU) activity of the external intercostal muscles before and after phrenicotomy.ResultsFollowing unilateral phrenic nerve section, mean peak SMU firing frequency of EI ipsilateral to the section was significantly greater when compared to control (15.9±0.7 vs. 12.1±0.5 Hz, p&lt;0.05). However, mean peak SMU firing frequency of the contralateral EI was unchanged (11.1±0.4 vs. 12±0.4 Hz, NS). Section of the contralateral phrenic nerve results in significantly higher mean peak SMU firing frequency of the contralateral EI (15.9±0.7 Hz, p&lt;0.05) when compared to before section.ConclusionThis study demonstrates that during HF‐SCS after C2 spinalization: 1) diaphragmatic afferents reflexly inhibit motor activity to the ipsilateral external intercostal muscles, and 2) the neural circuitry mediating the phrenic‐to‐intercostal reflex is preserved at a spinal level. Consequently, HF‐SCS applied to support ventilation in high tetraplegics with unilateral phrenic nerve injury may elicit increased activity of ipsilateral inspiratory intercostal muscles.Support or Funding InformationSupport: NIH‐NINDS (R01NS064157) and MetroHeath FoundationDisclosure: Dr. DiMarco is a Founder of and has a significant financial interest in Synapse BioMedical, Inc, a manufacturer of diaphragm pacing systems.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Sevoflurane for the treatment of refractory status epilepticus in the critical care unit

SummaryA 50‐year‐old woman with liver failure was admitted to critical care for refractory status epilepticus (RSE). Following tracheal intubation, sevoflurane was administered via the MIRUSTM system (Pall Medical, Dreieich, Germany). Following incremental increases in minimum alveolar concentration (MAC) from 0.3 to 1.0, there was a suppression of motor activity and continuous electroencephalogram (EEG) monitoring revealed suppression of seizure activity. Sevoflurane was progressively reduced to 0.3 MAC and the EEG recovered. Forty‐eight hours later, sevoflurane was discontinued followed by extubation. The patient was discharged from hospital a further 48 hours later. We argue that volatile anaesthetics can be titrated to a continuously monitored EEG in cases of RSE. Moreover, there now exists technology to safely and accurately administer volatile anaesthetics, which may have certain advantages over intravenous agents, in the critical care environment.