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Background: Deep brain stimulation (DBS) has demonstrated potential in mitigating Alzheimer's disease (AD). However, the invasive nature of DBS presents challenges for its application. The olfactory bulb (OB), showing early AD-related changes and extensive connections with memory regions, offers an attractive entry point for intervention, potentially restoring normal activity in deteriorating memory circuits., Aims: Our study examined the impact of electrically stimulating the OB on working memory as well as pathological and electrophysiological alterations in the OB, medial prefrontal cortex, hippocampus, and entorhinal cortex in amyloid beta (Aβ) AD model rats., Methods: Male Wistar rats underwent surgery for electrode implantation in brain regions, inducing Alzheimer's-like disease. Bilateral olfactory bulb (OB) electrical stimulation was performed for 1 hour daily to the OB of stimulation group animals for 18 consecutive days, followed by the evaluations of histological, behavioral, and local field potential signal processing., Results: OB stimulation counteracted Aβ plaque accumulation and prevented AD-induced working memory impairments. Furthermore, it prompted an increase in power across diverse frequency bands and enhanced functional connectivity, particularly in the gamma band, within the investigated regions during a working memory task., Conclusion: This preclinical investigation highlights the potential of olfactory pathway-based brain stimulation to modulate the activity of deep-seated memory networks for AD treatment. Importantly, the accessibility of this pathway via the nasal cavity lays the groundwork for the development of minimally invasive approaches targeting the olfactory pathway for brain modulation., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Respiratory patterns were investigated in male Sprague-Dawley rats throughout their lifespan, from weanling (1 month) to old age (24 months), under natural conditions. Both inter-breath interval (IBI) and respiratory volume (RV) were examined. Sample entropy suggested increasing irregularity in IBI but decreasing irregularity in RV until 12 months. According to detrended fluctuation analysis, alpha exponent of the IBI showed a bimodal pattern around the value 0.7. From 1-15 months, the alpha exponent for RV generally decreased to the value 0.5, but it increased again as the animals neared the end of their lifespan. Cross-sample entropy revealed increasing synchronization between IBI and RV until 12 months, then plateauing. Many measures demonstrated a transition around 12 months, potentially reflecting maturation of respiratory control mechanisms. The findings characterize complex dynamics of respiratory patterns across the rat lifespan, providing a normative foundation to identify deviations indicative of dysfunction or disease., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Navigational decision-making tasks, such as spatial working memory (SWM), rely highly on information integration from several cortical and sub-cortical regions. Performance in SWM tasks is associated with theta rhythm, including low-frequency oscillations related to movement and memory. The interaction of the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC), reflected in theta synchrony, is essential in various steps of information processing during SWM. We used a closed-loop neurofeedback (CLNF) system to upregulate theta power in the mPFC and investigate its effects on circuit dynamics and behavior in animal models. Specifically, we hypothesized that enhancing the power of the theta rhythm in the mPFC might improve SWM performance. Animals were divided into three groups: closed-loop (CL), random-loop (RL), and OFF (without stimulation). We recorded local field potential (LFP) in the mPFC while electrical reward stimulation contingent on cortical theta activity was delivered to the lateral hypothalamus (LH), which is considered one of the central reward-associated regions. We also recorded LFP in the vHPC to evaluate the related subcortical neural changes. Results revealed a sustained increase in the theta power in both mPFC and vHPC for the CL group. Our analysis also revealed an increase in mPFC-vHPC synchronization in the theta range over the stimulation sessions in the CL group, as measured by coherence and cross-correlation in the theta frequency band. The reinforcement of this circuit improved spatial decision-making performance in the subsequent behavioral results. Our findings provide direct evidence of the relationship between specific theta upregulation and SWM performance and suggest that theta oscillations are integral to cognitive processes. Overall, this study highlights the potential of adaptive CLNF systems in investigating neural dynamics in various brain circuits., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Methods We recruited 38 participants, equally distributed into healthy and asthma groups. Behavioral, neurophysiological, and lung function assessment tools were used in this study., Results Our behavioral data show that allergic asthma induces attention impairment. Additionally, the event-related potentials (ERP) analysis reveals that this attention deficit is associated with a disruption in cognitive processing capability in frontal brain areas. These behavioral and neurophysiological abnormalities were strongly correlated with disease severity and neuropsychiatric comorbidities of asthmatic patients., Conclusion Together, here we propose that disrupted neurophysiological responses in frontal brain areas might lead to attention impairments in patients with allergic asthma. These findings could help characterizing the neuro-pathophysiology of cognitive disorders in allergic asthma, possibly opening the way for development of novel treatment strategies.

Anxiety is among the most fundamental mammalian behaviors. Despite the physiological and pathological importance, its underlying neural mechanisms remain poorly understood. Here, we recorded the activity of olfactory bulb (OB) and medial prefrontal cortex (mPFC) of rats, which are critical structures to brain's emotional processing network, while exploring different anxiogenic environments. Our results show that presence in anxiogenic contexts increases the OB and mPFC regional theta activities. Also, these local activity changes are associated with enhanced OB-mPFC theta power- and phase-based functional connectivity as well as OB-to-mPFC information transfer. Interestingly, these effects are more prominent in the unsafe zones of the anxiogenic environments, compared to safer zones. This consistent trend of changes in diverse behavioral environments as well as local and long-range neural activity features suggest that the dynamics of OB-mPFC circuit theta oscillations might underlie different types of anxiety behaviors, with possible implications for anxiety disorders., (© 2024. The Author(s).)

Introduction: The positive effects of exercise on spatial memory and learning have been demonstrated in research. The olfactory sensory neurons (OSNs) respond to mechanical stimulation induced by nasal airflow which is associated with airflow intensity. Accordingly, nasal breathing can modulate brain oscillations in nonolfactory areas, and respiration-entrained oscillations aid the improvement of cognitive abilities. Given that aerobic exercise increases the rate of respiration and intensity of nasal airflow, this study evaluates the role of OSNs in mediating the effects of aerobic exercise on memory., Methods: We examined spatial memory following exercise in animal models of olfactory sensory neuron impairment (methimazole injection 300 mg/kg/week)., Results: Destroying OSNs significantly reduces olfactory bulb (OB) activity at delta and theta frequency bands as well as its coupling to respiration. More importantly, it abolished the positive effect of exercise on spatial memory (P<0.05)., Conclusion: The OB activity is one of the probable mechanisms for improving spatial memory following exercise., (Copyright© 2024 Iranian Neuroscience Society.)

This study aimed to investigate the effects of intranasal air-puffing on cognitive impairments and brain cortical activity following one night of partial sleep deprivation (PSD) in adults. A total of 26 healthy adults underwent the numerical Stroop test (NST) and electroencephalography (EEG) before and after one night of PSD. Following PSD, subjects in the treatment group ( n = 13) received nasal air-puffs (5 Hz, 3 min) before beginning the NST and EEG recording. Administration of nasal air-puffs in the treatment group restored the PSD-induced increase in error rate and decrease in reaction time and missing rate in the NST. Intranasal air-puffs recovered the PSD-induced augmentation of delta and theta power and the reduction of beta and gamma power in the EEG, particularly in the frontal lobes. Intranasal air-puffing also almost reversed the PSD-induced decrease in EEG signal complexity. Furthermore, it had a restorative effect on PSD-induced alteration in intra-default mode network functional connectivity in the beta and gamma frequency bands. Rhythmic nasal air-puffing can mitigate acute PSD-induced impairments in cognitive functions. It exerts part of its ameliorating effect by restoring neuronal activity in cortical brain areas involved in cognitive processing.

While breathing is a vital, involuntary physiological function, the mode of respiration, particularly nasal breathing, exerts a profound influence on brain activity and cognitive processes. This review synthesizes existing research on the interactions between nasal respiration and the entrainment of oscillations across brain regions involved in cognition. The rhythmic activation of olfactory sensory neurons during nasal respiration is linked to oscillations in widespread brain regions, including the prefrontal cortex, entorhinal cortex, hippocampus, amygdala, and parietal cortex, as well as the piriform cortex. The phase-locking of neural oscillations to the respiratory cycle, through nasal breathing, enhances brain inter-regional communication and is associated with cognitive abilities like memory. Understanding the nasal breathing impact on brain networks offers opportunities to explore novel methods for targeting the olfactory pathway as a means to enhance emotional and cognitive functions., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Aims: 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., Methods: 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., Results: 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., Conclusion: 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., (© 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Infertility is such an important issue in society today. In some cases of male infertility, the main cause is oxidative stress and the presence of reactive oxygen species in the environment or in sperm cells. All current techniques that measure oxidative stress, including the nitroblue tetrazolium Test, DNA Fragmentation Index, Malondialdehyde, and Endz Test are qualitative and semi-quantitative. These methods do not have good sensitivity and specificity. Semen samples from 50 infertile patients and 10 normal individuals were collected. The samples were examined for laboratory routine tests according to the WHO 2010 protocol. Oxidative stress tests, including DFI, NBT, and MDA, were performed for these two groups. Bioluminescence inhibition assay was performed for detection of O 2 .- in semen samples by aequorin. The normal individuals showed significantly better semen parameters than the patient's group. Significantly lower O 2 .- levels were seen in the patient's group compared to normal individuals. The cut-off value of O 2 .- levels in normal individuals was determined to be 8 × 10 5 RLU/s with a sensitivity of 100% and a specificity of 100%. Infertile patients, despite having reduced quality of semen parameters, have high O 2 .- levels, and this causes the intensity of bioluminescence to be quenched in these people., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Stuttering is a speech disorder characterized by impaired connections between brain regions involved in speech production. This study aimed to investigate functional connectivity and frequency power during rest in adults who stutter (AWS) compared to fluent adults (AWNS) in the dorsolateral prefrontal cortex (DLPFC), dorsolateral frontal cortex (DLFC), supplementary motor area (SMA), motor speech, angular gyrus (AG), and inferior temporal gyrus (ITG)., Materials and Methods: Fifteen AWS (3 females, 12 males) and fifteen age- and sex-matched AWNS (3 females, 12 males) participated in this study. All participants were native Persian speakers. Stuttering severity in the AWS group was assessed using the Persian version of the Stuttering Severity Instrument Fourth Edition (SSI-4). Resting-state electroencephalography (EEG) was recorded for 5 min while participants sat comfortably with their eyes open. We analyzed frequency band power across various frequency bands and investigated functional connectivity within the specified speech region., Results: Significant between-group differences were found in band powers including alpha, beta, delta, theta, and gamma, specifically in the premotor, SMA, motor speech, and frontal regions. AWS also showed increased coherence between the right motor speech region compared to controls. We demonstrate that the proposed hierarchical false discovery rate (FDR) method is the most effective for both simulations and experimental data. In the expected regions, this method revealed significant synchrony effects at an acceptable error rate of 5%., Conclusion: The results highlight disrupted functional connectivity in AWS at resting state, particularly in speech-related and associated areas. Given the complex neurological basis of developmental stuttering, robust neural markers are closely linked to this phenomenon. These markers include imbalanced activity within brain regions associated with speech and motor functions, coupled with impaired functional connectivity between these regions. The cortico-basal ganglia-thalamo-cortical system governs the dynamic interplay between cortical regions, with SMA as a key cortical site. It is hypothesized that the aberrant resting state functional connectivity will impact the language planning and motor execution necessary for fluent speech. Examining resting-state metrics as biomarkers could further elucidate the neural underpinnings of stuttering and guide intervention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Valaei, Bamdad, Golfam, Golmohammadi, Ameri and Raoufy.)

Several vaccines have been developed against SARS-CoV-2 and subsequently approved by national/international regulators. Detecting specific antibodies after vaccination enables us to evaluate the vaccine's effectiveness. We conducted a prospective longitudinal study among members of Tarbiat Modares University of Tehran, Iran, from 4 September 2021 until 29 December 2021. We aimed to compare the humoral immunogenicity of 3 vaccine types. Participants consisted of 462 adults. Anti-SARS-CoV-2 receptor-binding domain [RBD] IgG titer was compared in 3 groups, each vaccinated by available vaccines in Iran at the time: Oxford/AstraZeneca, COVIran Barekat, and Sinopharm. The median IgG titer was: 91.2, 105.6, 224.0 BAU/ml for Sinopharm, COVIran Barekat and Oxford/AstraZeneca respectively after the first dose; 195.2, 192.0, 337.6 BAU/ml after the second one. We also analyzed the frequency of antibody presence in each vaccine group, in the same order the results were 59.0%, 62.6% and 89.4% after the first dose and 92.1%,89.5% and 98.9% after the second. The comparison of results demonstrated that AstraZeneca vaccine is a superior candidate vaccine for COVID-19 vaccination out of the three. Our data also demonstrated statistically significant higher antibody titer among recipients with an infection history., (© 2023. The Author(s).)

Psychiatric disorders are common in patients with allergic asthma, and they can have a significant impact on their quality of life and disease control. Recent studies have suggested that there may be potential immune-brain communication mechanisms in asthma, which can activate inflammatory responses in different brain areas, leading to structural and functional alterations and behavioral changes. However, the precise mechanisms underlying these alterations remain unclear. In this paper, we comprehensively review the relevant research on asthma-induced brain structural and functional alterations that lead to the initiation and promotion of anxiety. We summarize the possible pathways for peripheral inflammation to affect the brain's structure and function. Our review highlights the importance of addressing neuropsychiatric disorders in the clinical guidelines of asthma, to improve the quality of life of these patients. We suggest that a better understanding of the mechanisms underlying psychiatric comorbidities in asthma could lead to the development of more effective treatments for these patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Brain functional deficits have been reported in asthma patients which can result in behavioral disorders like depression and anxiety. These deficits may be associated with factors like resistance to treatment, incorrect self-evaluation, and inadequate self-control. However, changes in the brain volume in allergic asthma and the effects of inhaled corticosteroids, the most common anti-inflammatory agents for asthma treatment, on these alterations remain largely unclear. Here, we evaluated depression and anxiety-like behavior as well as volume changes in different brain area, using magnetic resonance imaging in an animal model of allergic asthma with pretreatment of inhaled fluticasone propionate. Asthma-induced behavioral changes were partially, but not completely, prevented by pretreatment with inhaled fluticasone propionate. Volumetry findings showed that the allergen decreased volumes of the corpus callosum and subcortical white matter, as well as the septal region and hippocampus (especially CA1 and fimbria). However, volumes of neocortex, insular, and anterior cingulate cortex increased in asthmatic rats compared to controls. Namely, pretreatment with inhaled fluticasone propionate partially prevented asthma-induced brain volume changes, but not completely. These findings suggest that asthma is associated with structural alterations in the brain, which may contribute to the induction of psychological disorders. Thus, considering brain changes in the clinical assessments could have important implications for asthma treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Allergic asthma is a common chronic inflammatory condition associated with psychiatric comorbidities. Notably depression, correlated with adverse outcomes in asthmatic patients. Peripheral inflammation's role in depression has been shown previously. However, evidence regarding the effects of allergic asthma on the medial prefrontal cortex (mPFC)-ventral hippocampus (vHipp) interactions, an important neurocircuitry in affective regulation, is yet to be demonstrated. Herein, we investigated the effects of allergen exposure in sensitized rats on the immunoreactivity of glial cells, depression-like behavior, brain regions volume, as well as activity and connectivity of the mPFC-vHipp circuit. We found that allergen-induced depressive-like behavior was associated with more activated microglia and astrocytes in mPFC and vHipp, as well as reduced hippocampus volume. Intriguingly, depressive-like behavior was negatively correlated with mPFC and hippocampus volumes in the allergen-exposed group. Moreover, mPFC and vHipp activity were altered in asthmatic animals. Allergen disrupted the strength and direction of functional connectivity in the mPFC-vHipp circuit so that, unlike normal conditions, mPFC causes and modulates vHipp activity. Our results provide new insight into the underlying mechanism of allergic inflammation-induced psychiatric disorders, aiming to develop new interventions and therapeutic approaches for improving asthma complications., (Copyright © 2023 IBRO. Published by Elsevier Ltd. All rights reserved.)

Asthma is a heterogeneous disease in which the complexity of the breathing pattern reduces as the severity of the disease increases. Since the pathophysiological basis of reduced breathing pattern complexity in asthma is unclear, in this study, we investigated the effect of reducing inflammation using an inhaled corticosteroid (fluticasone propionate) on the breathing pattern of a rat model of asthma. Detrended fluctuation analysis, sample entropy, and cross-sample entropy analysis of both inter-breath interval and respiratory volume time series showed that early treatment with inhaled corticosteroids not only diminishes lung inflammation and airway hyper-responsiveness, but also has a protective effect against the reduction of breathing pattern complexity due to asthma. However, late treatment had a partial effect on asthma-induced respiratory pattern changes. Since inflammation is a key factor in shifting breathing dynamics away from normal fluctuations, these findings further emphasize the importance of early treatment of asthma with corticosteroids., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Mechanical ventilation (MV), as a life-saving procedure in critical patients, is a risk factor to develop of neurocognitive dysfunction and triggers of inflammation and apoptosis in the brain. Since diversion of breathing route to the tracheal tube diminishes brain activity entrained by physiological nasal breathing, we hypothesized that simulating nasal breathing using rhythmic air-puff (AP) into the nasal cavity of mechanically ventilated rats can reduce hippocampal inflammation and apoptosis in association with restoring respiration-coupled oscillations. We found that stimulating olfactory epithelium through applying rhythmic nasal AP, in association with reviving respiration-coupled brain rhythm, mitigates MV-induced hippocampal apoptosis and inflammation involving microglia and astrocytes. The current translational study opens a window for a novel therapeutic approach to reduce neurological complications induced by MV., (© 2023 Wiley Periodicals LLC.)

Aim: Low frequency stimulation (LFS) inhibits neuronal hyperexcitability following epileptic activity. However, knowledge about LFS' inhibitory mechanisms is lacking. Here, α 1 and α 2 adrenergic receptors' roles in mediating LFS inhibitory action on high-K + induced epileptiform activity (EA) was examined in rat hippocampal slices. Materials and methods: LFS (1 Hz, 900 pulses) was applied to the Schaffer collaterals. Whole-cell, patch clamp recording was used to measure changes in CA1 pyramidal neurons' excitability. By applying high-K + on hippocampal slices, EA was induced, and neuronal excitability increased. Results: When administered at the beginning of EA, LFS reduced neuronal excitability. In the presence of prazosin (10 µM, an α 1 adrenergic receptor antagonist) and yohimbine (5 µM, an α 2 adrenergic receptor antagonist), LFS' typically has a restorative impact on EA-induced membrane potential hyperpolarization and spike firing frequency, but this effect was reduced after high-K + washout; These antagonists did not have a significant effect on LFS' inhibitory action on spike firing during EA. Conclusion: These findings suggest that LFS' anticonvulsant effect, on neuronal hyperexcitability following high-K + EA, may be mediated partly through α adrenergic receptors in hippocampal slices.

Pharmacoresistant temporal lobe epilepsy affects millions of people around the world with uncontrolled seizures and comorbidities, like anxiety, being the most problematic aspects calling for novel therapies. The intrahippocampal kainic acid model of temporal lobe epilepsy is an appropriate rodent model to evaluate the effects of novel interventions, including glycolysis inhibition, on epilepsy-induced alterations. Here, we investigated kainic acid-induced changes in the dorsal hippocampus (dHPC) and basolateral amygdala (BLA) circuit and the efficiency of a glycolysis inhibitor, 2-deoxy D-glucose (2-DG), in resetting such alterations using simultaneous local field potentials (LFP) recording and elevated zero-maze test. dHPC theta and gamma powers were lower in epileptic groups, both in the baseline and anxiogenic conditions. BLA theta power was higher in baseline condition while it was lower in anxiogenic condition in epileptic animals and 2-DG could reverse it. dHPC-BLA coherence was altered only in anxiogenic condition and 2-DG could reverse it only in gamma frequency. This coherence was significantly correlated with the time in which the animals exposed themselves to the anxiogenic condition. Further, theta-gamma phase-locking was lower in epileptic groups in the dHPC-BLA circuit and 2-DG could considerably increase it., (© 2023. The Author(s).)

Aims: Allergic asthma is associated with anxiety-related behaviors, leading to poor quality of life. Previous studies mainly described the neuropathophysiology of asthma-induced anxiety. However, the effects of corticosteroids, the most common anti-inflammatory agents for asthma treatment, on the neurophysiological foundations of allergic asthma-induced anxiety are unexplored., Main Methods: Here, we evaluated lung and brain inflammation as well as anxiety in an animal model of allergic asthma pretreated with inhaled fluticasone propionate. Furthermore, to define the neurophysiological bases of these conditions, we studied the medial prefrontal cortex (mPFC)-amygdala circuit, which is previously shown to accompany asthma-induced anxiety., Key Findings: Our data showed that allergen induces anxiety, mPFC and amygdala inflammation, as well as disruptions in the local and long-range oscillatory activities within the mPFC-amygdala circuit. Interestingly, we observed a roughly consistent trend of changes with inhaled fluticasone pretreatment. Namely, the asthma-induced behavioral, inflammatory, and neurophysiological changes were partly, but not totally, prevented by inhaled fluticasone pretreatment., Significance: We suggest that early treatment of asthmatic patients with inhaled corticosteroids improves mPFC-amygdala circuit function by attenuating neuroinflammation leading to reduced anxiety. These findings could lead clinical guidelines of asthma to consider the neuropsychiatric disorders of patients in treatment recommendations., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Objectives: Default mode network (DMN) is a principal network that is more active at the baseline functional state of consciousness and spontaneous brain activity. Nasal breathing beyond the oxygen supply, entrained brain oscillations in widespread brain regions. Consistent with the important role of nasal breathing on neural oscillation for brain function, here we aimed to evaluate respiration entrained DMN rhythms., Materials and Methods: Using electroencephalography (EEG), we assessed the power spectral density and connectivity in DMN during the resting state among a group of sixteen healthy during three successive sessions. In addition to DMN, synchrony of the signal over the widespread cortical regions including somatosensory areas was investigated. Signal acquisition sessions consist of three times including nasal breathing, oral breathing, and nasal air-puff state that odorless air was puffed using a nasal cannula via an electrical valve (open duration of 630 ms) with a frequency of 0.2 Hz while subjects spontaneously breath orally., Results: Our analyses demonstrated that nasal airflow, during both nasal breathing and nasal air-puff states, enhanced the power and connectivity of DMN regions specially at higher frequency bands, particularly gamma ranges. Enhancement in brain areas activity and connectivity including DMN and somatosensory due to the nasal airflow were not affected even in the condition that subjects were not attending to the nasal air-puff., Conclusions: Nasal airflow promotes brain oscillations, particularly at the range of gamma that is very essential for higher brain functions., Competing Interests: Competing interests All authors declare no competing interest related to this manuscript., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Dopamine may be involved in the anticonvulsant action of deep brain stimulation (DBS). Therefore, ventral tegmental area (VTA), as a brain dopaminergic nucleus, may be a suitable target for DBS anticonvulsant action. This study investigated the effect of tonic and phasic stimulations of the VTA on seizure parameters. Seizures were induced in adult mice by sequential injections of a sub-convulsive dose of 35 mg/kg pentylenetetrazole (PTZ) every 48 h to develop the chemical kindling until the mice reached full kindled state (showing three consecutive seizure stages 4 or 5). Fully kindled mice received DBS once a day as tonic (square waves at 1 Hz; pulse duration: 200 μs; intensity: 300 μA; 600 pulses in 10 min) or phasic (square waves at 100 Hz; pulse duration: 200 μs; intensity: 300 μA; 8 trains of 10 pulses at 1 min interval; 800 pulses in 10 min) stimulations applied into their VTA for 4 days. A single dose of PTZ was injected after each DBS. Simultaneously electrocorticography and video recordings were performed during the seizure for accuracy in seizure severity parameters detection. Tonic but not phasic stimulation significantly decreased the epileptiform discharge duration and the seizure behavioral parameters such as maximum seizure stage, stage 5 duration, seizure duration. In addition, focal to generalized seizure latency increased following VTA tonic stimulation. These data suggest that tonic (but not phasic) stimulation of VTA before PTZ injection on 4 test days had anticonvulsant effects on PTZ-kindled seizures., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Temporal lobe epilepsy is the most drug-resistant type with the highest incidence among the other focal epilepsies. Metabolic manipulations are of great interest among others, glycolysis inhibitors like 2-deoxy D-glucose (2-DG) being the most promising intervention. Here, we sought to investigate the effects of 2-DG treatment on cellular and circuit level electrophysiological properties using patch-clamp and local field potentials recordings and behavioral alterations such as depression and anxiety behaviors, and changes in nitric oxide signaling in the intrahippocampal kainic acid model. We found that epileptic animals were less anxious, more depressed, with more locomotion activity. Interestingly, by masking the effect of increased locomotor activity on the parameters of the zero-maze test, no altered anxiety behavior was noted in epileptic animals. However, 2-DG could partially reverse the behavioral changes induced by kainic acid. The findings also showed that 2-DG treatment partially suppresses cellular level alterations while failing to reverse circuit-level changes resulting from kainic acid injection. Analysis of NADPH-diaphorase positive neurons in the CA1 area of the hippocampus revealed that the number of positive neurons was significantly reduced in dorsal CA1 of the epileptic animals and 2-DG treatment did not affect the diminishing effect of kainic acid on NADPH-d + neurons in the CA1 area. In the control group receiving 2-DG, however, an augmented NADPH-d + cell number was noted. These data suggest that 2-DG cannot suppress epileptiform activity at the circuit-level in this model of epilepsy and therefore, may fail to control the seizures in temporal lobe epilepsy cases., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Coma state and loss of consciousness are associated with impaired brain activity, particularly gamma oscillations, that integrate functional connectivity in neural networks, including the default mode network (DMN). Mechanical ventilation (MV) in comatose patients can aggravate brain activity, which has decreased in coma, presumably because of diminished nasal airflow. Nasal airflow, known to drive functional neural oscillations, synchronizing distant brain networks activity, is eliminated by tracheal intubation and MV. Hence, we proposed that rhythmic nasal air puffing in mechanically ventilated comatose patients may promote brain activity and improve network connectivity., Materials and Methods: We recorded electroencephalography (EEG) from 15 comatose patients (seven women) admitted to the intensive care unit because of opium poisoning and assessed the activity, complexity, and connectivity of the DMN before and during the nasal air-puff stimulation. Nasal cavity air puffing was done through a nasal cannula controlled by an electrical valve (open duration of 630 ms) with a frequency of 0.2 Hz (ie, 12 puff/min)., Results: Our analyses demonstrated that nasal air puffing enhanced the power of gamma oscillations (30-100 Hz) in the DMN. In addition, we found that the coherence and synchrony between DMN regions were increased during nasal air puffing. Recurrence quantification and fractal dimension analyses revealed that EEG global complexity and irregularity, typically seen in wakefulness and conscious state, increased during rhythmic nasal air puffing., Conclusions: Rhythmic nasal air puffing, as a noninvasive brain stimulation method, opens a new window to modifying the brain connectivity integration in comatose patients. This approach may potentially influence comatose patients' outcomes by increasing brain reactivity and network connectivity., (Copyright © 2021 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declarations of interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is a progressive disorder associated with cognitive dysfunction that alters the brain's functional connectivity. Assessing these alterations has become a topic of increasing interest. However, a few studies have examined different stages of AD from a complex network perspective that cover different topological scales. This study used resting state fMRI data to analyze the trend of functional connectivity alterations from a cognitively normal (CN) state through early and late mild cognitive impairment (EMCI and LMCI) and to Alzheimer's disease. The analyses had been done at the local (hubs and activated links and areas), meso (clustering, assortativity, and rich-club), and global (small-world, small-worldness, and efficiency) topological scales. The results showed that the trends of changes in the topological architecture of the functional brain network were not entirely proportional to the AD progression. There were network characteristics that have changed non-linearly regarding the disease progression, especially at the earliest stage of the disease, i.e., EMCI. Further, it has been indicated that the diseased groups engaged somatomotor, frontoparietal, and default mode modules compared to the CN group. The diseased groups also shifted the functional network towards more random architecture. In the end, the methods introduced in this paper enable us to gain an extensive understanding of the pathological changes of the AD process., (© 2022. The Author(s).)

Background: The intensity of respiratory symptoms and expiratory airflow limitations in asthma fluctuate over time. Some studies have reported variable complexity of the respiratory patterns in asthmatic patients. Thus, we conducted a novel study to assess the correlation between asthma severity and breathing pattern dynamics in newly-diagnosed asthmatic patients., Methods: A total of 20 newly-diagnosed asthmatic patients (7 male, 13 female) and 20 healthy cases (11 male, 9 female) were included. The respiratory patterns of all participants and the asthma severity for asthmatic patients were measured using a spirometer (before and after a bronchodilator exposure) and airflow recorder, respectively. The peak-to-peak intervals and the amplitude of peaks were considered as the inter-breath interval (IBI) and lung volume (LV) series. The Detrended Fluctuation Analysis (DFA), Sample Entropy (SampEn), Multi-scale Entropy (MSE), short-term (SD1) and long-term (SD2) variability, and IBI and LV Cross-Sample Entropy of the respiratory pattern dynamics were calculated using MATLAB (Mathwork, USA)., Results: Asthma patients showed notable increase in the average of sample entropy in both IBI and LV parameters (p = 0.025 and p = 0.018, respectively) and also decreased synchronization between IBI and LV (p = 0.042). The multi-scale sample entropy of both IBI and LV was significantly higher in asthmatic patients (p < 0.05). Furthermore, SD1 and SD2 were higher in the patients with asthma (p < 0.05). Significant correlations were detected between spirometric (forced expiratory flow (FEF) change, pre FEF, pre forced expiratory volume in one second (FEV1) / forced vital capacity (FVC), FVC change) and respiratory pattern (mean-IBI, mean-LV, mean-respiratory rate (RR), coefficient of variation (CV)-IBI, CV-LV, cross-sample entropy) parameters (p < 0.05). Furthermore, we identified a negative correlation between CV of IBI and asthma severity (r = -0.52, p = 0.021)., Conclusion: Here, we took a novel approach and observed increased irregularity (more complexity) in the breathing pattern of patients newly-diagnosed with asthma. Remarkable correlations were detected between breathing complexity markers and spirometric indices along with disease severity in asthmatic patients. Thus, our data suggests respiratory pattern indices could be utilized as an indicator of asthma and its severity. However, more clinical data are required to support this conclusion., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Asthma is a chronic inflammatory disease associated with a high prevalence of psychiatric disorders. There are specific brain networks responsible for emotional processes, including two important networks associated with psychiatric problems: the default mode network (DMN), which is more active in the resting state, and the salience network (SN), which is structurally connected to DMN. Although previous studies suggested that neuro-phenotypes of asthma may be recognizable by the neural activity of brain circuits, an association between the brain's functional alterations and psychiatric impairments induced by asthma remains unknown. We aimed to assess DMN and SN activity and its association with psychiatric indices and clinical parameters in asthmatic patients. Electroencephalography was recorded during the resting state with an awake and eyes-open condition in thirty-eight sex and age-matched subjects (19 atopic asthma patients and 19 healthy participants). Power spectrum and functional connectivity were computed for DMN and SN. We examined psychiatric disorders (including depression, anxiety, and stress) and pulmonary function using the DASS questionnaire and spirometry test, respectively. The results showed that DASS scores were significantly higher in asthmatic patients compared to healthy subjects. Asthmatic patients also demonstrate a significant enhancement in power and functional connectivity in the two networks. Notably, these power enhancements of the networks were correlated with psychiatric problems scores, pulmonary function, asthma duration, and poor asthma control. These results introduce new evidence for the association between altered brain activity, the existence of psychiatric disorders, and asthma-related features, including pulmonary function. Also, we provide new insights into asthma-induced inflammatory response and the importance of developing novel interventions and therapeutic strategies for managing allergic inflammation patients who suffer from concurrent psychiatric disorders., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Neural oscillations synchronize the activity of brain regions during cognitive functions, such as spatial working memory. Olfactory bulb (OB) oscillations are ubiquitous rhythms that can modulate neocortical and limbic regions. However, the functional connectivity between the OB and areas contributing to spatial working memory, such as the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC), is less understood. Hence, we investigated functional interaction between OB and the vHPC-mPFC circuit during the spatial working memory performance in rats. To this end, we analyzed the simultaneously recorded local field potentials from OB, vHPC, and mPFC when rats explored the Y-maze and compared the brain activities of correct trials vs. wrong trials. We found that coupling between the vHPC and mPFC was augmented during correct trials. The enhanced coherence of OB activity with the vHPC-mPFC circuit at delta (< 4 Hz) and gamma (50-80 Hz) ranges were observed during correct trials. The cross-frequency analysis revealed that the OB delta phase increased the mPFC gamma power within corrected trials, indicating a modulatory role of OB oscillations on mPFC activity during correct trials. Moreover, the correlation between OB oscillations and the vHPC-mPFC circuit was increased at the delta range during correct trials, exhibiting enhanced synchronized activity of these regions during the cognitive task. We demonstrated a functional engagement of OB connectivity with the vHPC-mPFC circuit during spatial working memory task performance., (© 2022. The Author(s).)

Neural synchrony in brain circuits is the mainstay of cognition, including memory processes. Alzheimer's disease (AD) is a progressive neurodegenerative disorder that disrupts neural synchrony in specific circuits, associated with memory dysfunction before a substantial neural loss. Recognition memory impairment is a prominent cognitive symptom in the early stages of AD. The entorhinal-hippocampal circuit is critically engaged in recognition memory and is known as one of the earliest circuits involved due to AD pathology. Notably, the olfactory bulb is closely connected with the entorhinal-hippocampal circuit and is suggested as one of the earliest regions affected by AD. Therefore, we recorded simultaneous local field potential from the olfactory bulb (OB), entorhinal cortex (EC), and dorsal hippocampus (dHPC) to explore the functional connectivity in the OB-EC-dHPC circuit during novel object recognition (NOR) task performance in a rat model of AD. Animals that received amyloid-beta (Aβ) showed a significant impairment in task performance and a marked reduction in OB survived cells. We revealed that Aβ reduced coherence and synchrony in the OB-EC-dHPC circuit at theta and gamma bands during NOR performance. Importantly, our results exhibit that disrupted functional connectivity in the OB-EC-dHPC circuit was correlated with impaired recognition memory induced by Aβ. These findings can elucidate dynamic changes in neural activities underlying AD, helping to find novel diagnostic and therapeutic targets., (© 2022. The Author(s).)

Allergic asthma affects both the respiratory function and central nervous system. Communication between the amygdala and respiratory control system is critical for regulating breathing function. To date, no study provides the effect of allergic inflammation on amygdala-respiration coupling. Here, we simultaneously recorded respiration and local field potentials of the amygdala during awake immobility in a rat model of allergic asthma. A decreased synchrony was found between amygdala and respiration in asthmatic rats. Allergen also reduced the modulatory effect of the respiration phase on amygdala power at delta, theta and gamma2 (80-120 Hz) frequencies. Moreover, in the animal model of allergic asthma, delta and theta oscillations strongly coordinate local gamma2 activity in the amygdala. These findings suggest that allergen can induce brain alterations and therefore shed light on future works to address how disruption of amygdala-respiration coupling contributes to respiratory dysfunction in allergic asthma., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Allergic asthma is a chronic inflammatory respiratory disease. Psychiatric disorders, including anxiety are associated with poorer treatment response and disease control in asthmatic patients. To date, there is no experimental evidence describing the role of peripheral inflammation on the oscillatory activities in the anterior cingulate cortex (ACC) and basolateral amygdala (BLA), two major brain structures modulating anxiety. In the present work we evaluated lung and brain inflammatory responses, anxiety-like behavior, in association with oscillatory features of the ACC-BLA circuit in an animal model of allergic inflammation. Our data showed that allergic inflammation induced anxiety-like behavior and reactivation of microglia and astrocytes in ACC and BLA. Allergic inflammation also enhanced neuronal activities and functional connectivity of the ACC-BLA circuit which were correlated with the level of anxiety. Together, we suggest that disruption in the dynamic oscillatory activities of the ACC-BLA circuit, maybe due to regional inflammation, is an underlying mechanism of allergic asthma-induced anxiety-like behavior. Our findings could pave the way for better understanding the neuro-pathophysiology of the psychiatric disorders observed in asthmatic patients, possibly leading to develop novel treatment strategies., (© 2022. The Author(s).)

Closed-loop approaches, setups, and experimental designs have been applied within the field of neuroscience to enhance the understanding of basic neurophysiology principles (closed-loop neuroscience; CLNS) and to develop improved procedures for modulating brain circuits and networks for clinical purposes (closed-loop neuromodulation; CLNM). The contents of this review are thus arranged into the following sections. First, we describe basic research findings that have been made using CLNS. Next, we provide an overview of the application, rationale, and therapeutic aspects of CLNM for clinical purposes. Finally, we summarize methodological concerns and critics in clinical practice of neurofeedback and novel applications of closed-loop perspective and techniques to improve and optimize its experiments. Moreover, we outline the theoretical explanations and experimental ideas to test animal models of neurofeedback and discuss technical issues and challenges associated with implementing closed-loop systems. We hope this review is helpful for both basic neuroscientists and clinical/ translationally-oriented scientists interested in applying closed-loop methods to improve mental health and well-being., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: The Electrocardiogram (ECG) is an important measure for diagnosing the presence or absence of heart arrhythmias. Premature ventricular contractions (PVC) is a relatively large arrhythmia occurring outside the normal tract and being triggered outside the Sino atrial (SA) node of heart., Objective: This study has focused on tunable Q-factor wavelet transform (TQWT) algorithm and statistical methods to detect PVC., Material and Methods: In this analytical and statistical study, 22 ECGs records were selected from the MIT/BIH arrhythmia database. In the first stage the noise of signal remove and then five sub-bands create by TQWT. In the second stage nine features (minimum, maximum, root mean square, mean, interquartile range, standard deviation (SD), skewness, and variance) extracted of ECG and then the best features selected by using analysis of variance (ANOVA) test. Finally, the system is evaluated by using the learning machines of support vector machine (SVM), the K-Nearest Neighbor (KNN), and artificial neural network (ANN)., Results: The best results were verified with KNN learning machine the sensitivity Se= 98.23% and accuracy Ac= 97.81%., Conclusion: A comparative analysis with the related existing methods shows the method proposed in this study is higher than the other method for classification PVC and can help physicians to classify normal and PVC heart signals in the screening of the patients with coronary artery diseases (CADs)., (Copyright: © Journal of Biomedical Physics and Engineering.)

The clinical use of opioids is restricted by its deleterious impacts on respiratory system. Gaining a better understanding of an individual's susceptibility to adverse opioid effects is important to recognize patients at risk. Ancestral drug addiction has been shown to be associated with alterations in drug responsiveness in the progenies. In the current study, we sought to evaluate the effects of preconception paternal morphine consumption on respiratory parameters in response to acute morphine in male offspring during adulthood, using plethysmography technique. Male Wistar rats administered 10 days of increasing doses of morphine in the period of adolescence. Thereafter, following a 30-day abstinence time, adult males copulated with naïve females. The adult male offspring were examined for breathing response to morphine. Our results indicated that sires who introduce chronic morphine during adolescence leads to increase irregularity of respiratory pattern and asynchronization between inter-breath interval (IBI) and respiratory volume (RV) time series in male offspring. These findings provide evidence that chronic morphine use by parents even before pregnancy can affect respiratory pattern and response to morphine in the offspring., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Low-frequency deep brain stimulation (LFS) inhibits neuronal hyperexcitability during epilepsy. Accordingly, the use of LFS as a treatment method for patients with drug-resistant epilepsy has been proposed. However, the LFS antiepileptic mechanisms are not fully understood. Here, the role of metabotropic glutamate receptors group I (mGluR I) in LFS inhibitory action on epileptiform activity (EA) was investigated. EA was induced by increasing the K + concentration in artificial cerebrospinal fluid (ACSF) up to 12 mM in hippocampal slices of male Wistar rats. LFS (1 Hz, 900 pulses) was delivered to the bundles of Schaffer collaterals at the beginning of EA. The excitability of CA1 pyramidal neurons was assayed by intracellular whole-cell recording. Applying LFS reduced the firing frequency during EA and substantially moved the membrane potential toward repolarization after a high-K + ACSF washout. In addition, LFS attenuated the EA-generated neuronal hyperexcitability. A blockade of both mGluR 1 and mGluR 5 prevented the inhibitory action of LFS on EA-generated neuronal hyperexcitability. Activation of mGluR I mimicked the LFS effects and had similar inhibitory action on excitability of CA1 pyramidal neurons following EA. However, mGluR I agonist's antiepileptic action was not as strong as LFS. The observed LFS effects were significantly attenuated in the presence of a PKC inhibitor. Altogether, the LFS' inhibitory action on neuronal hyperexcitability following EA relies, in part, on the activity of mGluR I and a PKC-related signaling pathway., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Cognitive functions such as working memory require integrated activity among different brain regions. Notably, entorhinal cortex (EC) activity is associated with the successful working memory task. Olfactory bulb (OB) oscillations are known as rhythms that modulate rhythmic activity in widespread brain regions during cognitive tasks. Since the OB is structurally connected to the EC, we hypothesized that OB could modulate EC activity during working memory performance. Herein, we explored OB-EC functional connectivity during spatial working memory performance by simultaneous recording local field potentials when rats performed a Y-maze task. Our results showed that the coherence of delta, theta, and gamma-band oscillations between OB and EC was increased during correct trials compared to wrong trials. Cross-frequency coupling analyses revealed that the modulatory effect of OBs low-frequency phase on EC gamma power and phase was enhanced when animals correctly performed working memory task. The influx of information from OB to EC was also increased at delta and gamma bands within correct trials. These findings indicated that the modulatory influence of OB rhythms on EC oscillations might be necessary for successful working memory performance.

Mechanical ventilation (MV) can result in long-term brain impairments that are resistant to treatment. The mechanisms underlying MV-induced brain function impairment remain unclear. Since nasal airflow modulates brain activity, here we evaluated whether reinstating airflow during MV could influence the memory performance of rats after recovery. Rats were allocated into two study groups: one group received rhythmic air-puff into the nasal cavity during MV and a control group that underwent ventilation without air-puff. During MV, air-puffs induced time-locked event potentials in OB, mPFC and vHPC and significantly increased the oscillatory activity at the air-puff frequency. Furthermore, in mPFC and vHPC, (but not in OB), delta and theta oscillations were more prominent during air-puff application. After recovery, working memory performance was significantly higher in the air-puff group compared to control. Our study thus suggests a promising non-invasive brain stimulation approach to alleviate the neurological complications of prolonged mechanical ventilation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Allergic rhinitis (AR) is a chronic inflammatory disease frequently associated with a deficit in learning and memory. Working memory is an important system for decision making and guidance, which depends on interactions between the ventral hippocampus (vHipp) and the prelimbic prefrontal cortex (plPFC). It is still unclear whether AR influences the activity and coupling of these brain areas, which consequently may impair working memory. The current study aimed to examine alterations of the vHipp-plPFC circuit in a rat model of AR. Our results show decreased working memory performance in AR animals, accompanied by a reduction of theta and gamma oscillations in plPFC. Also, AR reduces coherence between vHipp and plPFC in both theta and gamma frequency bands. Cross-frequency coupling analyses confirmed a reduced interaction between hippocampal theta and plPFC gamma oscillations. Granger causality analysis revealed a reduction in the causal effects of vHipp activity on plPFC oscillations and vice versa. A significant correlation was found between working memory performance with disruption of functional connectivity in AR animals. In summary, our data show that in AR, there is a deficit of functional coupling between hippocampal and prefrontal network, and suggest that this mechanism might contribute to working memory impairment in individuals with AR., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Multiple Sclerosis (MS) is a demyelinating disease leading to long-term neurological deficit due to unsuccessful remyelination and axonal loss. Currently, there are no satisfactory treatments for progressive MS somewhat due to the lack of an adequate animal model for studying the mechanisms of disease progression and screening new drugs., New Method: Lysolecithin (LPC) or agarose-gel loaded LPC (AL-LPC) were applied to mouse optic nerve behind the globe via a minor surgery. Agarose loading was used to achieve longer time of LPC exposure and subsequently long-lasting demyelination., Results: The lesion sites characterized by luxol fast blue (LFB), FluoroMyelin, Bielschowsky's staining, and immunostaining showed extensive demyelination and axonal damage. The loss of Retinal ganglion cells (RGCs) in the corresponding retinal layer was shown by immunostaining and H&E staining. Visual evoked potential (VEP) recordings showed a significant increase in the latency of the P1 wave and a decrease in the amplitude of the P1N1 wave., Comparison With Existing Methods: The new approach with a very minor surgery seems to be more feasible and reproducible compared to stereotaxic LPC injection to optic chiasm. Our data revealed prolonged demyelination, axonal degeneration and RGCs loss in both AL-LPC and LPC groups; however, these pathologies were more extensive in the AL-LPC group., Conclusion: The optimized model provides a longer demyelination time frame and axonal damage followed by RGC degeneration; which is of exceptional interest in investigating axonal degeneration mechanisms and screening the new drugs for progressive MS., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: The modulatory effect of deep inspiration (DI) on airway constriction is impaired in asthma. However, mechanisms underlying this impairment are not clear. Since there is evidence indicating that Rho-kinase activation mediates force maintenance under oscillatory strain, we investigated the impact of Rho-kinase inhibition on the bronchodilatory effect of DI in ovalbumin (OVA) sensitized guinea pigs., Materials and Methods: forty-eight male Dunkin Hartley guinea pigs were divided into 8 groups including saline/ constant, saline/DI, OVA/constant, OVA/DI, Rho-I/OVA/constant, Rho-I/OVA/DI, OVA-Rho-I/MCh/constant, and OVA-Rho-I/MCh/DI. Animals were subjected to 12 inhalations of OVA or saline aerosol. Guinea pigs in Rho-I/OVA/constant or DI groups were treated with the Rho-kinase inhibitor (Rho-I) (Y-27632, 1 mM aerosols) prior to the last 8 allergen inhalations and OVA-Rho-I/MCh/constant or DI groups received Y-27632 at the end of allergen sensitization protocol before methacholine challenge. The bronchodilatory effect of DI in guinea pigs that were exposed to methacholine was assessed by using an animal ventilator. The bronchodilatory effect was assessed using several parameters: the airway pressure maintenance, airway pressure recovery, and decline of airway pressure., Results: Results indicated that application of Y-27632 prior to methacholine challenge reduces the airway smooth muscle ability to maintain pressure and also causes further decline in airway pressure in OVA-sensitized animals undergone DI. However, the inhibition of Rho-kinase before OVA inhalations had minimal effect., Conclusion: We propose that alteration of Rho-kinase signaling pathway may be one of the mechanisms underlying the impairment of DI-induced bronchodilation in OVA-sensitized guinea pigs.

Background: The clinical characteristics of the novel coronavirus disease (COVID-19) were diverse and unspecific. Here, we identified the associated factors with surviving of COVID-19 ICU patients based on the clinical characteristics of patients admitted to one of the Corona Centre Hospitals of Iran., Materials and Methods: This cohort study was performed retrospectively from February to June 2020 on 133 COVID-19 patients admitted to 4 intensive care units of Masih Daneshvari Hospital in Tehran, Iran. Demographic, medical, clinical manifestation at admission, laboratory parameters and outcome data were obtained from medical records. Also the SOFA and APACHE II scores were calculated. All data were analyzed using SPSS (version 23, IBM Corp.) software., Results: The median (IQR) age of the patients was 62.0 (54.0-72.0) years in total. RT-PCR of throat swab SARS-CoV-2 in 80 patients (60.2%) was positive. Total mortality rate was 57.9 percent (77 patients). Dyspnea, hypertension and chronic pulmonary diseases were significantly common in non-survivors than survivors (p<0.05). Both SOFA and APACHE II scores were significantly higher in the non-survivors (p<0.05). Also other significant differences were observed in other parameters of the study., Conclusion: The mortality rate of COVID-19 patients admitted to ICU is generally high. Dyspnea as initial presentation and comorbidity, especially hypertension and pulmonary diseases, may be associated with higher risk of severe disease and consequent mortality rate. Also, higher SOFA and APACHE II scores could indicate higher mortality in patients admitted to ICU., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright© 2020 National Research Institute of Tuberculosis and Lung Disease.)

Aims: There is much controversy regarding whether cardiovascular events increase in women with polycystic ovary syndrome (PCOS) with aging. Considering the lack of possibility of certain investigations in humans, animal models of PCOS may be suitable resources to obtain the useful data needed. In this study; we aimed to investigate whether cardiac function and tolerance to ischemia/reperfusion (I/R) injury worsen in postmenopausal rats, who had PCOS at younger ages, compared to controls., Main Methods: The hearts of aged rats with a history of PCOS and their controls were isolated and perfused in a Langendorff apparatus. Values of hemodynamic parameters, including left ventricular systolic pressure (LVSP), left ventricular developed pressure (LVDP), rate pressure product (RPP) and peak rates of positive and negative changes in left ventricular pressure (±dp/dt) were recorded using a power lab system. Blood serum levels of total testosterone (TT) and estradiol (E2) were determined by ELISA kits. Generalized Estimating Equation Model and t-student unpaired test results were used to compare the findings documented between two groups., Key Findings: No statistically significant differences were observed in hemodynamic parameters of the heart including, LVSP, LVDP, RPP and ±dp/dt, between the rats of two groups of study, at baseline or before ischemia and after I/R. Nor were any significant differences observed in the levels of two hormones between the two groups (p > 0.05)., Significance: History of PCOS during reproductive ages should not be considered an important risk factor for reduction in cardiac contractile function or less tolerance to I/R injury during the postmenopausal period., (Copyright © 2020. Published by Elsevier Inc.)

Objective: Sepsis is a leading cause of mortality and morbidity in infants. Although the measures of autonomic dysfunction (e.g., reduced heart rate variability) predict mortality in sepsis, the mechanism of sepsis-induced autonomic dysfunction has remained elusive. The nucleus of the solitary tract (NTS) is a vital structure for the integrated autonomic response to physiological challenges. In the present study we hypothesized that sepsis alters the excitability of NTS neurons in a rat model of neonatal sepsis (14-day-old rats)., Methods and Results: Sepsis was induced by intraperitoneal injection of cecal slurry (CS) in rat neonates. The presence of autonomic dysfunction was confirmed by observing a significant reduction in both short-term and long-term heart rate variably following CS injection. We investigated the effect of polymicrobial sepsis on the electrophysiological properties of the medial NTS neurons using a whole cell patch clamp recording. Our results showed that the resting membrane potential in regular spiking neurons was significantly less polarized in the septic group (-37.6 ± 1.76 mv) when compared with the control group (-54.7 ± 1.73 mv, P < 0.001). The number of spontaneous action potentials in the septic group was also significantly higher than the control group (P < 0.05). In addition, the frequency and amplitude of the spontaneous excitatory post synaptic potentials was significantly higher in neurons recorded in the septic group (P < 0.001). Interestingly, regular spiking cells in the CS group exhibited a rebound action potential following hyperpolarization. Injection of depolarizing currents was associated with lower first spike latency and changes in rise slope of action potential (P < 0.001)., Conclusions: We showed that polymicrobial sepsis increases the excitability of regular spiking cells in the medial NTS. These alterations can potentially affect neural coding and thus may contribute to an abnormal homeostatic or allostatic physiological response to sepsis and systemic inflammation.

The mechanisms involved in the anti-seizure effects of low-frequency stimulation (LFS) have not been completely determined. However, G i -protein-coupled receptors, including D 2 -like receptors, may have a role in mediating these effects. In the present study, the role of D 2 -like receptors in LFS' anti-seizure action was investigated. Rats were kindled with semi-rapid (6 stimulations per day), electrical stimulation of the hippocampal CA1 area. In LFS-treated groups, subjects received four trials of LFS at 5 min, 6 h, 24 h, and 30 h following the last kindling stimulation. Each LFS set occurred at 5 min intervals, and consisted of 4 trains. Each train contained 200, 0/1 ms long, monophasic square wave pulses at 1 Hz. Haloperidol (D 2 -like receptors antagonist, 2 µm) and/or bromocriptine (D 2 -like receptors agonist 2 µg/µlit) were microinjected into the lateral ventricle immediately after the last kindling, before applying LFS. Obtained results showed that applying LFS in fully-kindled subjects led to a depotentiation-like decrease in kindling-induced potentiation and reduced the amplitude and rise slope of excitatory and inhibitory post-synaptic currents in whole-cell recordings from CA1 pyramidal neurons. In addition, LFS restored the kindling-induced, spatial learning and memory impairments in the Barnes maze test. A D 2 -like receptor antagonist inhibited these effects of LFS, while a D 2 -like receptor agonist mimicked these effects. In conclusion, a depotentiation-like mechanism may be involved in restoring LFS' effects on learning and memory, and synaptic plasticity. These effects depend on D 2 -like receptors activity., (Copyright © 2020 Elsevier B.V. All rights reserved.)