{"title":"TRPA1 contributes to respiratory depression from tobacco aerosol.","authors":"Sichong Chen, Nobuaki Takahashi, Momoka Okahara, Hideki Kashiwadani, Yasuo Mori, Liying Hao, Tomoyuki Kuwaki","doi":"10.1016/j.resp.2024.104385","DOIUrl":"https://doi.org/10.1016/j.resp.2024.104385","url":null,"abstract":"<p><p>Transient receptor potential ankyrin-1 (TRPA1) is expressed in the trigeminal nerves in the nasal cavity. It detects irritant chemicals such as formalin and acrolein, induces respiratory depression to protect against further inhalation, and elicits avoidance behavior. Although tobacco smoke contains formalin, acrolein, and other irritant chemicals, the possible contribution of TRPA1 to protection against tobacco smoke has yet to be fully understood. In this study, we compared respiratory and behavioral responses to an aerosol of tobacco smoke between TRPA1 conditional knockout mice and the controls. We also compared the effect of aerosols from the smoke of traditional standard tobacco and a recently developed heated tobacco product. As expected, respiratory depression by tobacco aerosol was observed only in the TRPA1 intact mice and was associated with increased trigeminal activation. Meanwhile, mice did not avoid or even prefer tobacco aerosol in a TRPA1-independent manner, contrary to our expectations. Repeated exposure to tobacco aerosol resulted in lung inflammation in a TRPA1-independent manner. Aerosols from a heated tobacco product showed no significant effect as in traditional tobacco smoke. These results indicate that TRPA1 contributes to acute protection from tobacco smoke by inducing respiratory depression but not to the safety of the lungs in repeated exposure. Tobacco aerosol contains attractive substances for mice. Heated tobacco product aerosol contains less TRPA1 activating substances and less inflammation evoking than traditional tobacco smoke.</p>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":" ","pages":"104385"},"PeriodicalIF":1.9,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elder Pereira Nascimento, Fernando Zanela da Silva Arêas, Swyanne Rosenete Scantelbury Neves Tavares, Beatriz Campelo Monteiro, Ellem Nara Tananta Dantas, Renato Campos Freire, Cassia da Luz Goulart, Fernando de Almeida Val, Jorge Henriques, Guilherme Peixoto Tinoco Arêas
{"title":"THE ACUTE EFFECT OF BILATERAL CATHODIC TRANSCRANIAL DIRECT CURRENT STIMULATION ON RESPIRATORY MUSCLE STRENGTH AND ENDURANCE.","authors":"Elder Pereira Nascimento, Fernando Zanela da Silva Arêas, Swyanne Rosenete Scantelbury Neves Tavares, Beatriz Campelo Monteiro, Ellem Nara Tananta Dantas, Renato Campos Freire, Cassia da Luz Goulart, Fernando de Almeida Val, Jorge Henriques, Guilherme Peixoto Tinoco Arêas","doi":"10.1016/j.resp.2024.104382","DOIUrl":"https://doi.org/10.1016/j.resp.2024.104382","url":null,"abstract":"<p><strong>Introduction: </strong>Transcranial direct current stimulation (tDCS) is a non-invasive technique with therapeutic potential, especially in respiratory muscle training (RMT) in pathological conditions such as chronic obstructive pulmonary disease and heart failure.</p><p><strong>Objective: </strong>To evaluate the effect of bilateral cathodic tDCS on respiratory muscle strength and endurance in healthy young and elderly women.</p><p><strong>Methods: </strong>An experimental, randomized study with 80 participants divided into young and old women, subdivided into intervention and sham control groups. The participants were evaluated by spirometry and dynamic muscle strength tests before and after the one session intervention. tDCS was applied with cathode electrodes positioned bilaterally in the motor area.</p><p><strong>Results: </strong>The elderly women in the intervention group showed significant improvement in dynamic inspiratory muscle strength (S-Index) and dominant hand strength, with moderate to large effect sizes. The young women showed a significant increase only in the strength of the dominant hand, with no improvement in inspiratory muscle strength. There were no significant differences in ventilatory parameters, including Maximal Ventilatory Capacity, in any of the age groups.</p><p><strong>Conclusion: </strong>Bilateral cathodic tDCS was effective in increasing dynamic inspiratory muscle strength and dominant hand strength in elderly women, with more pronounced effects compared to young women. The technique did not produce significant changes in maximal ventilatory capacity in any of the age groups, suggesting that the response to tDCS may vary with age, being more beneficial in elderly women.</p>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":" ","pages":"104382"},"PeriodicalIF":1.9,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tomas Buday, Mariana Brozmanova, Janka Jakusova, Abdullah Al Owesie, Laura Sophie Ertl, Daniela Mokra, Juliana Hanusrichterova, Tatiana Burjanivova, Zuzana Biringerova, Jana Plevkova
{"title":"Impact of microbial diversity on inflammatory cytokines and respiratory pattern measured in whole-body plethysmography in guinea pig models.","authors":"Tomas Buday, Mariana Brozmanova, Janka Jakusova, Abdullah Al Owesie, Laura Sophie Ertl, Daniela Mokra, Juliana Hanusrichterova, Tatiana Burjanivova, Zuzana Biringerova, Jana Plevkova","doi":"10.1016/j.resp.2024.104384","DOIUrl":"10.1016/j.resp.2024.104384","url":null,"abstract":"<p><strong>Objective: </strong>This study investigates the breathing patterns and immune status of guinea pigs raised under specific pathogen-free (SPF) conditions compared to conventionally bred (CON).</p><p><strong>Methods: </strong>Breathing pattern parameters were assessed using whole-body plethysmography (WBP) during quiet breathing and saline nebulisation. Blood and bronchoalveolar lavage fluid (BALF) were analysed for white blood cell, neutrophil and eosinophil counts, and cytokine levels (TNF-α, IL-1β, IL-4).</p><p><strong>Results: </strong>SPF guinea pigs exhibited higher tidal volume, expired volume, minute volume, and airflow parameters than CON guinea pigs. The immune analysis revealed lower white blood cell counts and IL-4 levels in SPF guinea pigs. These findings indicate that SPF guinea pigs have different respiratory and immune responses than CON guinea pigs.</p><p><strong>Conclusion: </strong>The study highlights that the maturation processes affecting breathing pattern parameters in SPF guinea pigs differ significantly from those in CON guinea pigs. This suggests potential limitations of SPF animals in respiratory physiology research due to their different immune and respiratory responses.</p>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":" ","pages":"104384"},"PeriodicalIF":1.9,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Glycolytic metabolism modulation on spinal neuroinflammation and vital functions following cervical spinal cord injury.","authors":"Pauline Michel-Flutot, Arnaud Mansart, Stéphane Vinit","doi":"10.1016/j.resp.2024.104383","DOIUrl":"10.1016/j.resp.2024.104383","url":null,"abstract":"<p><p>High spinal cord injuries (SCIs) often result in persistent diaphragm paralysis and respiratory dysfunction. Chronic neuroinflammation within the damaged spinal cord after injury plays a prominent role in limiting functional recovery by impeding neuroplasticity. In this study, we aimed to reduce glucose metabolism that supports neuroinflammatory processes in an acute preclinical model of C2 spinal cord lateral hemisection in rats. We administered 2-deoxy-D-glucose (2-DG; 200 mg/kg/day s.c., for 7 days) and evaluated the effect on respiratory function and chondroitin sulfate proteoglycans (CSPGs) production around spinal phrenic motoneurons. Contrary to our initial hypothesis, our 2-DG treatment did not have any effect on diaphragm activity and CSPGs production in injured rats, although slight increases in tidal volume were observed. Unexpectedly, it led to deleterious effects in uninjured (sham) animals, characterized by increased ventilation and CSPGs production. Ultimately, our results seem to indicate that this 2-DG treatment paradigm may create a neuroinflammatory state in healthy animals, without affecting the already established spinal inflammation in injured rats.</p>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":" ","pages":"104383"},"PeriodicalIF":1.9,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ethanol abolishes ventilatory long-term facilitation and blunts the ventilatory response to hypoxia in female rats.","authors":"Aaron L Silverstein, Warren J Alilain","doi":"10.1016/j.resp.2024.104373","DOIUrl":"10.1016/j.resp.2024.104373","url":null,"abstract":"<p><p>Obstructive sleep apnea (OSA) is a breathing disorder in which airway obstruction during sleep leads to periodic bouts of inadequate (hypopneic) or absent (apneic) ventilation despite neurorespiratory effort. Repetitive apneic and hypopneic exposures can induce intermittent hypoxemia and lead to a host of maladaptive behavioral and physiological outcomes. Intermittent hypoxia treatment (IH), which consists of alternating exposure to hypoxic and normal air, can induce a long-lasting increase in breathing motor outputs called long term facilitation (LTF). IH models key aspects of the hypoxemia experienced during OSA and LTF might serve to prevent OSA or ameliorate its severity by stimulating ventilatory output during or after apnea/hypopnea. Ethanol consumption prior to sleep exacerbates existing OSA, but it is unknown how ethanol affects LTF expression. Thus, we hypothesized that ethanol treatment would attenuate LTF expression and the magnitude of the ventilatory response during acute hypoxic exposure. We administered either low-dose (0.8 g/kg) or high-dose (3 g/kg) ethanol or saline to adult female Sprague-Dawley rats through intraperitoneal injection and then measured subjects' ventilatory output by whole-body plethysmography during baseline, a 5 by 3-minute moderate IH protocol (hypoxia: F<sub>i</sub>O<sub>2</sub> = 0.11, Normoxia: room air), and for one hour following the end of IH. Results indicate that low-dose ethanol abolishes LTF of respiratory rate and minute ventilation and trends suggest that low-dose ethanol might attenuate respiratory rate and minute ventilation during acute hypoxic exposure. While high-dose ethanol significantly diminished subjects' respiratory rate and minute ventilation during hypoxia, LTF expression was not significantly different between high-dose ethanol and saline-treated subjects. Overall, data indicate that ethanol exposure dramatically attenuates LTF expression following IH treatment and impairs ventilatory responses to hypoxia in a dose-dependent manner. Such findings inspire further consideration of ethanol's negative effects upon endogenous compensatory mechanisms for repeated hypoxic exposure, both in the context of OSA and beyond.</p>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":" ","pages":"104373"},"PeriodicalIF":1.9,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laszlo Markasz , Hamid Mobini-Far , Richard Sindelar
{"title":"Early and late postnatal lung distribution of collagen type VI in preterm and term infants","authors":"Laszlo Markasz , Hamid Mobini-Far , Richard Sindelar","doi":"10.1016/j.resp.2024.104366","DOIUrl":"10.1016/j.resp.2024.104366","url":null,"abstract":"<div><div>Collagen type VI (COL6) is an important component of the extracellular matrix (EM) and may have a major role in lung development and disease. Studies on COL6 expression during lung development are mainly based on animal models. The aim of the study was to define COL6 expression pattern in lung parenchyma in infants with different lung maturational stages.</div><div>COL6 expression in 115 lung samples from deceased newborn infants (21–41 weeks’ gestational age; 0–228 days’ postnatal age) was studied by immunohistochemistry combined with digital image analysis.</div><div>The distribution of COL6 expression was generally heterogeneous in the lung parenchyma of preterm and term infants. The size of the high-density and low-density areas appeared with logarithmic correlation and COL6 defined the basement membrane (BM) with a prominent expression around the air spaces in the canalicular stage during the first postnatal week. Infants at the alveolar stage showed linear correlation and a fine filamentous appearance during the first week of postnatal life, similarly to adults.</div><div>COL6 is condensed to areas corresponding to the BM during the first postnatal week of the canalicular stage of lung development. After the first postnatal week COL6 expression changes to a microfibrillar appearance in the ECM, similar to the pattern that characterizes the later alveolar stage and adults. The localization of COL6 during the canalicular and saccular stages might have a higher impact on lung development than the amount of COL6.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"332 ","pages":"Article 104366"},"PeriodicalIF":1.9,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yan-Jhih Shen , Ping-Hsun Ou , Yan-Cheng Shen , Ching Jung Lai
{"title":"Role of endogenous nerve growth factor in laryngeal airway hyperreactivity and laryngeal inflammation induced by intermittent hypoxia in rats","authors":"Yan-Jhih Shen , Ping-Hsun Ou , Yan-Cheng Shen , Ching Jung Lai","doi":"10.1016/j.resp.2024.104372","DOIUrl":"10.1016/j.resp.2024.104372","url":null,"abstract":"<div><div>Obstructive sleep apnea, characterized by airway exposure to intermittent hypoxia (IH), is associated with laryngeal airway hyperreactivity (LAH) and laryngeal inflammation. The sensitization of capsaicin-sensitive superior laryngeal afferents (CSSLAs) by inflammatory mediators has been implicated in the pathogenesis of LAH. Nerve growth factor (NGF) is an inflammatory mediator that acts on tropomyosin receptor kinase A (TrkA) and the p75 neurotrophin receptor (p75<sup>NTR</sup>) to induce lower airway hyperresponsiveness. In this study, we investigated the role of NGF in the development of LAH and laryngeal inflammation induced by IH in anesthetized rats. Compared with rats subjected to room air exposure for 14 days, rats with 14-day IH exposure exhibited augmented reflex apneic responses to the laryngeal provocation of three different chemical stimulants of CSSLAs, resulting in LAH. The apneic responses to laryngeal stimulants were abolished by either perineural capsaicin treatment (a procedure that selectively blocks the conduction of CSSLAs) or denervation of the superior laryngeal nerves, suggesting that the reflex was mediated through CSSLAs. The IH-induced LAH was significantly attenuated by daily treatment with anti-NGF antibody, but was unaffected by daily treatment with immunoglobulin G. IH exposure also induced laryngeal inflammation as evidenced by increases in laryngeal levels of NGF, lipid peroxidation, tumor necrosis factor-α, interleukin-1β, TrkA, and p75<sup>NTR</sup>. Similarly, IH-induced laryngeal inflammation was significantly reduced by daily treatment with anti-NGF antibody. We concluded that NGF contributes to the development of LAH and laryngeal inflammation induced by IH in rats. The LAH may result from the sensitizing effect of NGF on CSSLAs.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"332 ","pages":"Article 104372"},"PeriodicalIF":1.9,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J.C. Brown, R. Boat, N.C. Williams, M.A. Johnson, G.R. Sharpe
{"title":"Prior self-control exertion decreases pre-frontal cortex oxygenation during a CO2 rebreathing challenge but does not affect perceptions of dyspnoea or tolerance time","authors":"J.C. Brown, R. Boat, N.C. Williams, M.A. Johnson, G.R. Sharpe","doi":"10.1016/j.resp.2024.104371","DOIUrl":"10.1016/j.resp.2024.104371","url":null,"abstract":"<div><h3>Introduction</h3><div>Dyspnoea perception is influenced by a complex interplay of physiological, psychological, and environmental factors. Recently, we showed that males with high trait self-control experience less dyspnoea and persist for longer in a carbon dioxide (CO<sub>2</sub>) rebreathing challenge than males with low trait self-control. As self-control can also vary within individuals (state self-control), the primary aim of the present study was to investigate whether prior self-control exertion influenced perceptions of dyspnoea and tolerance of a CO<sub>2</sub> rebreathing challenge in healthy young males. We also used functional near-infrared spectroscopy (fNIRS) to assess haemodynamic activity of the pre-frontal cortex (PFC) which is a region of interest (ROI) in dyspnoea research, and the primary brain region associated with exertion of self-control.</div></div><div><h3>Methods</h3><div>In a within-subjects design, fifteen healthy young males completed an easy (congruent) Stroop task (control condition) and a difficult (incongruent) Stroop task (prior self-control exertion, experimental condition) followed by a CO<sub>2</sub> rebreathing challenge until the limit of tolerance. Changes in oxyhaemoglobin (ΔO<sub>2</sub>Hb) and deoxyhaemoglobin (ΔHHb) were assessed continuously in the Stroop task and CO<sub>2</sub> rebreathing challenge. During the CO<sub>2</sub> rebreathing challenge, dyspnoea intensity and unpleasantness were rated every 30 s.</div></div><div><h3>Results</h3><div>Prior self-control exertion did not affect perceptions of dyspnoea or tolerance time in the CO<sub>2</sub> rebreathing challenge (all <em>P</em> > 0.05). ΔO<sub>2</sub>Hb from baseline was higher in the left (+38 %) and right (+44 %) pre-frontal cortices during the difficult Stroop task than the easy Stroop task (both <em>P</em> < 0.05). During the subsequent CO<sub>2</sub> rebreathing challenge, ΔO<sub>2</sub>Hb was attenuated following prior self-control exertion in the left PFC.</div></div><div><h3>Conclusions</h3><div>Although prior self-control exertion decreased pre-frontal cortex oxygenation during a subsequent CO<sub>2</sub> rebreathing challenge, there was no change in tolerance time or perceptions of dyspnoea.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"332 ","pages":"Article 104371"},"PeriodicalIF":1.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Athena Rivera, Sarah N. Framnes-DeBoer, Deanna M. Arble
{"title":"The MC4R agonist, setmelanotide, is associated with an improvement in hypercapnic chemosensitivity and weight loss in male mice","authors":"Athena Rivera, Sarah N. Framnes-DeBoer, Deanna M. Arble","doi":"10.1016/j.resp.2024.104370","DOIUrl":"10.1016/j.resp.2024.104370","url":null,"abstract":"<div><div>Obesity increases the risk of respiratory diseases that reduce respiratory chemosensitivity, such as Obesity Hypoventilation Syndrome and sleep apnea. Recent evidence suggests that obesity-related changes in the brain, including alterations in melanocortin signaling via the melanocortin-4 receptor (MC4R), may underly altered chemosensitivity. Setmelanotide, an MC4R agonist, causes weight loss in both humans and animal models. However, it is unknown the extent to which setmelanotide affects respiratory chemosensitivity independent of body weight loss. The present study uses diet-induced obese, male C57bl/6 J mice to determine the extent to which acute setmelanotide treatment affects the hypercapnic ventilatory response (HCVR). We find that ten days of daily setmelanotide treatment at 1 mg/kg, but not 0.2 mg/kg, is sufficient to cause weight loss and increase HCVR. In a separate group of animals, we find that we can emulate setmelanotide’s effect on weight loss by restricting daily calories to match the hypophagia triggered by setmelanotide. These pair-fed animals exhibit improvements in HCVR similar to those who receive setmelanotide. We conclude that acute treatment with setmelanotide is as effective as weight loss at improving respiratory hypercapnic chemosensitivity.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"332 ","pages":"Article 104370"},"PeriodicalIF":1.9,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142627115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aaron A. Jones , Jose R. Oberto , Marissa C. Ciesla , Yasin B. Seven , Latoya L. Allen , Elisa J. Gonzalez-Rothi, Gordon S. Mitchell
{"title":"Enhanced phrenic motor neuron BDNF expression elicited by daily acute intermittent hypoxia is undermined in rats with chronic cervical spinal cord injury","authors":"Aaron A. Jones , Jose R. Oberto , Marissa C. Ciesla , Yasin B. Seven , Latoya L. Allen , Elisa J. Gonzalez-Rothi, Gordon S. Mitchell","doi":"10.1016/j.resp.2024.104369","DOIUrl":"10.1016/j.resp.2024.104369","url":null,"abstract":"<div><div>Acute intermittent hypoxia (AIH) elicits spinal neuroplasticity and is emerging as a potential therapeutic modality to improve respiratory and non-respiratory motor function in people with chronic incomplete spinal cord injury (SCI). Brain-derived neurotrophic factor (BDNF) is necessary and sufficient for moderate AIH-induced phrenic long-term facilitation, a well-studied form of respiratory motor plasticity. Repetitive daily AIH (dAIH) enhances BDNF expression within the phrenic motor neurons of normal rats, but its effects on BDNF after chronic cervical spinal cord injury (cSCI) are unknown. In contrast to AIH, chronic intermittent hypoxia (CIH), simulating that experienced during sleep apnea, elicits neuropathology and undermines plasticity. Here, we tested the hypothesis that daily AIH <em>vs</em> CIH differentially regulate phrenic motor neuron BDNF expression in spinally intact and injured rats. Rats with and without C2 hemisection (C2Hx; 8 weeks post-injury) were exposed to 28 days of: 1) sham normoxia (Nx, 21 % O<sub>2</sub>); 2) daily AIH (dAIH: 10, 5 min episodes of 10.5 % O<sub>2</sub> per day; 5 min normoxic intervals); 3) mild CIH (CIH5/5: 5 min of 10.5 % O<sub>2</sub>, 5 min intervals, 8 hrs/day); or 4) moderate CIH (CIH2/2: 2 min of 10.5 % O<sub>2</sub>, 2 min intervals, 8 hrs/day). After 28 days of daily exposure (<em>i.e</em>., 12 weeks post-injury), BDNF immunoreactivity was assessed within phrenic motor neurons identified <em>via</em> retrograde cholera toxin B fragment labeling. In intact rats, daily AIH increased BDNF protein levels in phrenic motor neurons (∼31 %) but not in rats with C2Hx. CIH had no effects on phrenic motor neuron BDNF levels in intact rats, although there was a trend towards increased phrenic motor neuron BDNF after C2Hx, suggesting the need for further study. Since dAIH effects on phrenic motor neuron BDNF are not observed in rats with chronic cervical SCI, the potential of dAIH to enhance BDNF-dependent phrenic motor plasticity may be suppressed by conditions prevailing with chronic cSCI.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"332 ","pages":"Article 104369"},"PeriodicalIF":1.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142627114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}