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.
{"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":"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}
Pub Date : 2024-12-15DOI: 10.1016/j.resp.2024.104382
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
Introduction: 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.
Objective: To evaluate the effect of bilateral cathodic tDCS on respiratory muscle strength and endurance in healthy young and elderly women.
Methods: 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.
Results: 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.
Conclusion: 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.
{"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}
Pub Date : 2024-12-06DOI: 10.1016/j.resp.2024.104384
Tomas Buday, Mariana Brozmanova, Janka Jakusova, Abdullah Al Owesie, Laura Sophie Ertl, Daniela Mokra, Juliana Hanusrichterova, Tatiana Burjanivova, Zuzana Biringerova, Jana Plevkova
Objective: This study investigates the breathing patterns and immune status of guinea pigs raised under specific pathogen-free (SPF) conditions compared to conventionally bred (CON).
Methods: 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).
Results: 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.
Conclusion: 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.
目的:本研究调查了在特定无病原体(SPF)条件下饲养的豚鼠与传统饲养(CON)的豚鼠的呼吸模式和免疫状况:本研究调查了在特定无病原体(SPF)条件下饲养的豚鼠与传统饲养(CON)的豚鼠的呼吸模式和免疫状态:方法:在安静呼吸和生理盐水雾化时使用全身胸透(WBP)评估呼吸模式参数。分析血液和支气管肺泡灌洗液(BALF)中的白细胞、中性粒细胞和嗜酸性粒细胞计数以及细胞因子水平(TNF-α、IL-1β、IL-4):结果:SPF豚鼠的潮气量、呼气量、分钟量和气流参数均高于CON豚鼠。免疫分析显示,SPF豚鼠的白细胞计数和IL-4水平较低。这些结果表明,SPF 豚鼠的呼吸和免疫反应与 CON 豚鼠不同:本研究强调,影响 SPF 豚鼠呼吸模式参数的成熟过程与 CON 豚鼠的成熟过程存在显著差异。这表明,由于豚鼠的免疫和呼吸反应不同,SPF 动物在呼吸生理学研究中可能存在局限性。
{"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}
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.
{"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}
Pub Date : 2024-11-25DOI: 10.1016/j.resp.2024.104373
Aaron L Silverstein, Warren J Alilain
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: FiO2 = 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.
阻塞性睡眠呼吸暂停(OSA)是一种呼吸障碍,在睡眠过程中,气道阻塞会导致周期性通气不足(低通气)或不通气(呼吸暂停),尽管神经呼吸已经做出努力。反复的呼吸暂停和低通气暴露可诱发间歇性低氧血症,并导致一系列不适应的行为和生理结果。间歇性低氧治疗(IH)包括交替暴露于低氧和正常空气中,可诱导呼吸运动输出的持久增加,称为长期促进(LTF)。IH 模拟了 OSA 时所经历的低氧血症的主要方面,而 LTF 可在呼吸暂停/低通气过程中或之后刺激通气输出,从而预防 OSA 或减轻其严重程度。睡眠前摄入乙醇会加重现有的 OSA,但乙醇如何影响 LTF 的表达尚不清楚。因此,我们假设乙醇治疗会减弱LTF的表达和急性缺氧暴露时通气反应的程度。我们通过腹腔注射给成年雌性 Sprague-Dawley 大鼠注射低剂量(0.8 克/千克)或高剂量(3 克/千克)乙醇或生理盐水,然后在基线、5 分种 3 分钟中度 IH 方案(缺氧:FiO2 = 0.11,正常缺氧:室内空气)和 IH 结束后一小时内通过全身胸透测量受试者的通气量。结果表明,低剂量乙醇可消除呼吸频率和分钟通气量的LTF,其趋势表明,在急性缺氧暴露期间,低剂量乙醇可能会减弱呼吸频率和分钟通气量。虽然高剂量乙醇会显著降低受试者在缺氧时的呼吸频率和分钟通气量,但高剂量乙醇和生理盐水处理的受试者之间的 LTF 表达并无显著差异。总之,数据表明,乙醇暴露会显著降低 IH 处理后的 LTF 表达,并以剂量依赖的方式损害对缺氧的通气反应。这些发现启发人们进一步考虑乙醇对反复缺氧暴露的内源性代偿机制的负面影响,无论是在 OSA 还是其他情况下。
{"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}
Pub Date : 2024-11-21DOI: 10.1016/j.resp.2024.104366
Laszlo Markasz , Hamid Mobini-Far , Richard Sindelar
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.
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.
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.
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.
{"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}
Pub Date : 2024-11-19DOI: 10.1016/j.resp.2024.104372
Yan-Jhih Shen , Ping-Hsun Ou , Yan-Cheng Shen , Ching Jung Lai
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 (p75NTR) 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 p75NTR. 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.
阻塞性睡眠呼吸暂停的特点是气道暴露于间歇性缺氧(IH),与喉气道高反应性(LAH)和喉部炎症有关。炎症介质对辣椒素敏感的喉上传入(CSSLA)的致敏作用与 LAH 的发病机制有关。神经生长因子(NGF)是一种炎症介质,可作用于肌球蛋白受体激酶 A(TrkA)和 p75 神经营养素受体(p75NTR),诱导下呼吸道高反应性。在本研究中,我们研究了 NGF 在麻醉大鼠 IH 诱导的 LAH 和喉部炎症发展中的作用。与暴露于室内空气中 14 天的大鼠相比,暴露于 IH 14 天的大鼠对三种不同的 CSSLAs 化学刺激物的喉刺激表现出更强的反射性呼吸暂停反应,从而导致 LAH。对喉部刺激物的呼吸暂停反应可通过硬膜外辣椒素治疗(一种选择性阻断 CSSLAs 传导的方法)或去神经支配喉上神经而消失,这表明反射是通过 CSSLAs 介导的。IH诱导的LAH在每天使用抗NGF抗体治疗后明显减弱,但在每天使用免疫球蛋白G治疗后则不受影响。IH暴露还诱导喉部炎症,表现为喉部NGF、脂质过氧化物、肿瘤坏死因子-α、白细胞介素-1β、TrkA和p75NTR水平的升高。同样,每天使用抗 NGF 抗体治疗可显著减轻 IH 引起的喉部炎症。我们的结论是,NGF有助于IH诱导的大鼠LAH和喉部炎症的发展。LAH可能是NGF对CSSLAs的增敏作用所致。
{"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}
Pub Date : 2024-11-14DOI: 10.1016/j.resp.2024.104371
J.C. Brown, R. Boat, N.C. Williams, M.A. Johnson, G.R. Sharpe
Introduction
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 (CO2) 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 CO2 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.
Methods
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 CO2 rebreathing challenge until the limit of tolerance. Changes in oxyhaemoglobin (ΔO2Hb) and deoxyhaemoglobin (ΔHHb) were assessed continuously in the Stroop task and CO2 rebreathing challenge. During the CO2 rebreathing challenge, dyspnoea intensity and unpleasantness were rated every 30 s.
Results
Prior self-control exertion did not affect perceptions of dyspnoea or tolerance time in the CO2 rebreathing challenge (all P > 0.05). ΔO2Hb 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 P < 0.05). During the subsequent CO2 rebreathing challenge, ΔO2Hb was attenuated following prior self-control exertion in the left PFC.
Conclusions
Although prior self-control exertion decreased pre-frontal cortex oxygenation during a subsequent CO2 rebreathing challenge, there was no change in tolerance time or perceptions of dyspnoea.
{"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}
Pub Date : 2024-11-13DOI: 10.1016/j.resp.2024.104370
Athena Rivera, Sarah N. Framnes-DeBoer, Deanna M. Arble
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.
{"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}
Pub Date : 2024-11-12DOI: 10.1016/j.resp.2024.104369
Aaron A. Jones , Jose R. Oberto , Marissa C. Ciesla , Yasin B. Seven , Latoya L. Allen , Elisa J. Gonzalez-Rothi, Gordon S. Mitchell
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 vs 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 % O2); 2) daily AIH (dAIH: 10, 5 min episodes of 10.5 % O2 per day; 5 min normoxic intervals); 3) mild CIH (CIH5/5: 5 min of 10.5 % O2, 5 min intervals, 8 hrs/day); or 4) moderate CIH (CIH2/2: 2 min of 10.5 % O2, 2 min intervals, 8 hrs/day). After 28 days of daily exposure (i.e., 12 weeks post-injury), BDNF immunoreactivity was assessed within phrenic motor neurons identified via 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.
{"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}