Systemic LPS induces spinal inflammatory gene expression and impairs phrenic long-term facilitation following acute intermittent hypoxia

Huxtable, Adrianne G.; Smith, Sally J.; Vinit, Stéphane; Watters, Jyoti J.; Mitchell, Gordon S.

doi:10.1152/japplphysiol.01347.2012

Cited by 73 publications

(105 citation statements)

References 73 publications

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“…Frequency plasticity is also evident after AIH, but is more variable than pLTF (Baker-Herman and Mitchell, 2008). Systemic inflammation, induced by a high or low-dose of systemic LPS, had no effect on frequency plasticity 3 hours post-LPS (Huxtable et al, 2013; Vinit et al, 2011). However, 24 hours after a low-dose of LPS, frequency plasticity was abolished and was not restored by the NSAID ketoprofen (Huxtable et al, 2013).…”

Section: Integrative Examplesmentioning

confidence: 95%

“…Systemic inflammation, induced by a high or low-dose of systemic LPS, had no effect on frequency plasticity 3 hours post-LPS (Huxtable et al, 2013; Vinit et al, 2011). However, 24 hours after a low-dose of LPS, frequency plasticity was abolished and was not restored by the NSAID ketoprofen (Huxtable et al, 2013). The lack of restoration of frequency plasticity may be due to an independent or nonspecific effect of ketoprofen, which also reduced frequency plasticity in control animals (Huxtable et al, 2013).…”

Section: Integrative Examplesmentioning

confidence: 95%

“…One commonly studied form of respiratory motor plasticity, phrenic long-term facilitation (pLTF, induced by acute IH (AIH), 3 × 5 min episodes of hypoxia; (Devinney et al, 2013; Gonzalez-Rothi et al, 2015) is exquisitely sensitive to even low levels of systemic inflammation, since a low systemic dose of LPS induces CNS inflammation and abolishes pLTF for at least 24 hours (Huxtable et al, 2013). Increased inflammatory gene expression was observed immediately following LPS, but returned to baseline levels by 24 hours, despite the continued absence of pLTF.…”

Section: Cns Inflammation and Neuroplasticitymentioning

confidence: 99%

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The impact of inflammation on respiratory plasticity

Hocker

Stokes

Powell

et al. 2017

Experimental Neurology

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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.

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Section: Integrative Examplesmentioning

confidence: 95%

Section: Integrative Examplesmentioning

confidence: 95%

Section: Cns Inflammation and Neuroplasticitymentioning

confidence: 99%

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The impact of inflammation on respiratory plasticity

Hocker

Stokes

Powell

et al. 2017

Experimental Neurology

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“…This has important implications since neuroinflammation is associated with neuronal loss (Kawashita et al, 2011; Vitner et al, 2012), motoneuron degeneration (Chiu et al, 2013), and also a blunted capacity for neuroplasticity in respiratory pathways (Huxtable et al, 2013, 2011). In other lysosomal storage disorders, apoptosis and microglial activation occur in parallel during disease progression.…”

Section: Discussionmentioning

confidence: 99%

Neuropathology in respiratory-related motoneurons in young Pompe (Gaa) mice

Turner

Hoyt

ElMallah

et al. 2016

Respiratory Physiology & Neurobiology

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Respiratory and/or lingual dysfunction are among the first motor symptoms in Pompe disease, a disorder resulting from absence or dysfunction of the lysosomal enzyme acid α-glucosidase (GAA). Here, we histologically evaluated the medulla, cervical and thoracic spinal cords in 6 weeks old asymptomatic Pompe (Gaa−/−) mice to determine if neuropathology in respiratory motor regions has an early onset. Periodic acid-Schiff (PAS) staining indicated glycogen accumulation was exclusively occurring in Gaa−/− hypoglossal, mid-cervical and upper thoracic motoneurons. Markers of DNA damage (Tunel) and ongoing apoptosis (Cleaved Caspase 3) did not co-localize with PAS staining, but were prominent in a medullary region which included the nucleus tractus solitarius, and also in the thoracic spinal dorsal horn. We conclude that respiratory-related motoneurons are particularly susceptible to GAA deficiency and that neuronal glycogen accumulation and neurodegeneration may occur independently in early stage disease. The data support early therapeutic intervention in Pompe disease.

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“…Stress in several forms, such as underlying disease or changes in housing conditions, blocks multiple forms of spinal plasticity in rats. 34,35 Thus, it is possible that AIH treatment did not improve ladder walking when combined with treadmill training alone because of the stresses induced by the treadmill experience itself. Nevertheless, the presence of a trend toward moderate recovery in all treadmill-trained rats suggests that treadmill training might have separate effects on ladder task performance, possibly through mechanisms distinct from those of AIH plus task-specific training.…”

Section: Involuntary Walking Training Does Not Improve Ladder Performmentioning

confidence: 99%

Delayed Intervention with Intermittent Hypoxia and Task Training Improves Forelimb Function in a Rat Model of Cervical Spinal Injury

Prosser-Loose

Hassan

Mitchell

et al. 2015

Journal of Neurotrauma

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The reduction of motor, sensory and autonomic function below the level of an incomplete spinal cord injury (SCI) has devastating consequences. One approach to restore function is to induce neural plasticity as a means of augmenting spontaneous functional recovery. Acute intermittent hypoxia (AIH-brief exposures to reduced O2 levels alternating with normal O2 levels) elicits plasticity in respiratory and nonrespiratory somatic spinal systems, including improvements in ladder walking performance in rats with incomplete SCI. Here, we determined whether delayed treatment with AIH, with or without concomitant motor training, could improve motor recovery in a rat model of incomplete cervical SCI. In a randomized, blinded, sham-controlled study, rats were exposed to AIH for 7 days beginning at 4 weeks post-SCI, after much spontaneous recovery on a horizontal ladder-crossing task had already occurred. For up to 2 months post-treatment, AIH-treated rats made fewer footslips on the ladder task compared with sham-treated rats. Importantly, concomitant ladder-specific motor training was needed to elicit AIH-induced improvements, such that AIH-treated SCI rats receiving no motor training or nontask-specific treadmill training during the treatment week did not show improvements over sham-treated rats with SCI. AIH treatment combined with task-specific training did not improve recovery on two different reach-to-grasp tasks, however, nor on tasks involving unskilled forepaw use. In brief, our results indicate that task-specific training is needed for AIH to improve ladder performance in a rat model of incomplete cervical SCI.

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Systemic LPS induces spinal inflammatory gene expression and impairs phrenic long-term facilitation following acute intermittent hypoxia

Cited by 73 publications

References 73 publications

The impact of inflammation on respiratory plasticity

The impact of inflammation on respiratory plasticity

Neuropathology in respiratory-related motoneurons in young Pompe (Gaa) mice

Delayed Intervention with Intermittent Hypoxia and Task Training Improves Forelimb Function in a Rat Model of Cervical Spinal Injury

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