The impact of inflammation on respiratory plasticity

Abstract

Breathing is a vital homeostatic behavior and must be precisely regulated throughout life. Clinical conditions commonly associated with inflammation, undermine respiratory function may involve plasticity in respiratory control circuits to compensate and maintain adequate ventilation. Alternatively, other clinical conditions may evoke maladaptive plasticity. Yet, we have only recently begun to understand the effects of inflammation on respiratory plasticity. Here we review some of common models used to investigate the effects of inflammation and discuss the impact of inflammation on nociception, chemosensory plasticity, medullary respiratory centers, motor plasticity in motor neurons and respiratory frequency, and adaptation to high altitude. We provide new data suggesting glial cells contribute to CNS inflammatory gene expression after 24 hours of sustained hypoxia and inflammation induced by 8 hours of intermittent hypoxia inhibits long-term facilitation of respiratory frequency. We also discuss how inflammation can have opposite effects on the capacity for plasticity, whereby it is necessary for increases in the hypoxic ventilatory response with sustained hypoxia but inhibits phrenic long term facilitation after intermittent hypoxia. This review highlights gaps in our knowledge about the effects of inflammation on respiratory control (development, age, and sex differences). In summary, data to date suggest plasticity can be either adaptive or maladaptive and understanding how inflammation alters the respiratory system is crucial for development of better therapeutic interventions to promote breathing and for utilization of plasticity as a clinical treatment.

Minocycline alters expression of inflammatory markers in autonomic brain areas and ventilatory responses induced by acute hypoxia

“…The present study shows that AH induced an increase in the mRNA levels of IL-6, IL-1 , TNF and MMP9 in specific brain regions involved with cardiorespiratory control, corroborating previous data in the literature that suitable oxygen perfusion in cells is extremely important for the maintenance of their vital functions, whereas low oxygen levels trigger the induction of transcription factors Hocker et al, 2017;Prabhakar & Semenza, 2015;Stokes, Arbogast, Moya, Fu, & Powell, 2017;).…”

“…A common attribute of disruption of homeostasis is inflammation. In addition, increasing evidence supports a dynamic role for inflammation either by promoting or by inhibiting different forms of plasticity within the brain (Hocker, Stokes, Powell, & Huxtable, ). Physiological perturbations such as hypoxia promote transcriptional responses that initiate gene‐specific regulation to improve cellular oxygenation and decrease ATP expenditure (Cummins & Keogh, ; Cummins et al ., ; Kiernan, Smith, Mitchell, & Watters, ; Oliver et al., ; Taylor & Cummins, ).…”

Enhancement of excitatory transmission in NTS neurons projecting to ventral medulla of rats exposed to sustained hypoxia is blunted by minocycline

“…; Hocker et al . ). In the present study, in which minocycline treatment was used in whole animals, we cannot determine whether the observed effect of this drug was in the CNS or at the periphery.…”

“…Previous studies have documented that sustained hypoxia can trigger peripheral (carotid body) and central inflammation (NTS region) (Liu et al 2009;Popa et al 2011;Hocker et al 2017). In the present study, in which minocycline treatment was used in whole animals, we cannot determine whether the observed effect of this drug was in the CNS or at the periphery.…”

Contribution of Oxidative Stress and Inflammation to the Neurogenic Hypertension Induced by Intermittent Hypoxia

“…Most of the cellular responses and adaptations to hypoxia are mediated by the hypoxia-inducible factor-1α (HIF-1α) ( Prabhakar and Semenza, 2012 ; Peng et al, 2014 ). NF-κB is a critical transcriptional activator of HIF-1α and it is necessary for the accumulation of HIF-1α during hypoxia ( Hocker et al, 2017 ). On the other hand, hypoxia may directly activate the NF-κB factor, promoting the transcription of pro-inflammatory cytokines ( Eltzschig and Carmeliet, 2011 ).…”