Lipopolysaccharide attenuates phrenic long-term facilitation following acute intermittent hypoxia

Vinit, Stéphane; Windelborn, James A.; Mitchell, Gordon S.

doi:10.1016/j.resp.2011.02.008

Cited by 60 publications

(62 citation statements)

References 34 publications

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“…Since our limited analysis does not allow differentiation between microglial phenotypes (Colton, 2009; David and Kroner, 2011; Hanisch and Kettenmann, 2007; Nikodemova et al, 2013), we do not know if CTB–SAP microglial activation is beneficial or detrimental. Since systemic and neuro-inflammation both increase breathing frequency at rest and impair breathing capacity during chemoreflex activation (Huxtable et al, 2011, 2013; Vinit et al, 2011), activated microglia may impair breathing capacity in CTB–SAP rats. This possibility awaits further investigation.…”

Section: Discussionmentioning

confidence: 99%

Respiratory function after selective respiratory motor neuron death from intrapleural CTB–saporin injections

Nichols

Vinit

Bauernschmidt

et al. 2015

Experimental Neurology

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Amyotrophic lateral sclerosis (ALS) causes progressive motor neuron degeneration, paralysis and death by ventilatory failure. In rodent ALS models: 1) breathing capacity is preserved until late in disease progression despite major respiratory motor neuron death, suggesting unknown forms of compensatory respiratory plasticity; and 2) spinal microglia become activated in association with motor neuron cell death. Here, we report a novel experimental model to study the impact of respiratory motor neuron death on compensatory responses without many complications attendant to spontaneous motor neuron disease. In specific, we used intrapleural injections of cholera toxin B fragment conjugated to saporin (CTB–SAP) to selectively kill motor neurons with access to the pleural space. Motor neuron survival, CD11b labeling (microglia), ventilatory capacity and phrenic motor output were assessed in rats 3–28 days after intrapleural injections of: 1) CTB–SAP (25 and 50 μg), or 2) unconjugated CTB and SAP (i.e. control; (CTB + SAP). CTB–SAP elicited dose-dependent phrenic and intercostal motor neuron death; 7 days post-25 μg CTB–SAP, motor neuron survival approximated that in end-stage ALS rats (phrenic: 36 ± 7%; intercostal: 56 ± 10% of controls; n = 9; p < 0.05). CTB–SAP caused minimal cell death in other brainstem or spinal cord regions. CTB–SAP: 1) increased CD11b fractional area in the phrenic motor nucleus, indicating microglial activation; 2) decreased breathing during maximal chemoreceptor stimulation; and 3) diminished phrenic motor output in anesthetized rats (7 days post-25 μg, CTB–SAP: 0.3 ± 0.07 V; CTB + SAP: 1.5 ± 0.3; n = 9; p < 0.05). Intrapleural CTB–SAP represents a novel, inducible model of respiratory motor neuron death and provides an opportunity to study compensation for respiratory motor neuron loss.

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Section: Discussionmentioning

confidence: 99%

Respiratory function after selective respiratory motor neuron death from intrapleural CTB–saporin injections

Nichols

Vinit

Bauernschmidt

et al. 2015

Experimental Neurology

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“…Despite the fact that antibiotic drugs are injected into the animal and extreme care about the "pseudo-sterile" conditions were used during surgery, bacterial infection could occur and impact the entire study planned to be performed on this model. For example, systemic inflammation induced by Lipopolysaccharide injection will abolish respiratory neuroplasticity 22 , and could impact and/or hide the subsequent spontaneous neuroplasticity or the effect of putative restorative strategies. The monitoring of the body temperature throughout this procedure could also participate to the success of making this experimental model.…”

Section: Discussion Technical Difficulties Of Making the C2 Injury Modelmentioning

confidence: 99%

A Murine Model of Cervical Spinal Cord Injury to Study Post-lesional Respiratory Neuroplasticity

Keomani

Deramaudt

Petitjean

et al. 2014

JoVE

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Citation: Keomani, E., Deramaudt, T.B., Petitjean, M., Bonay, M., Lofaso, F., Vinit, S. A Murine Model of Cervical Spinal Cord Injury to Study Postlesional Respiratory Neuroplasticity. J. Vis. Exp. (87), e51235, doi:10.3791/51235 (2014). AbstractA cervical spinal cord injury induces permanent paralysis, and often leads to respiratory distress. To date, no efficient therapeutics have been developed to improve/ameliorate the respiratory failure following high cervical spinal cord injury (SCI). Here we propose a murine pre-clinical model of high SCI at the cervical 2 (C2) metameric level to study diverse post-lesional respiratory neuroplasticity. The technique consists of a surgical partial injury at the C2 level, which will induce a hemiparalysis of the diaphragm due to a deafferentation of the phrenic motoneurons from the respiratory centers located in the brainstem. The contralateral side of the injury remains intact and allows the animal recovery. Unlike other SCIs which affect the locomotor function (at the thoracic and lumbar level), the respiratory function does not require animal motivation and the quantification of the deficit/recovery can be easily performed (diaphragm and phrenic nerve recordings, whole body ventilation). This preclinical C2 SCI model is a powerful, useful, and reliable pre-clinical model to study various respiratory and non-respiratory neuroplasticity events at different levels (molecular to physiology) and to test diverse putative therapeutic strategies which might improve the respiration in SCI patients. Video LinkThe video component of this article can be found at

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“…Phrenic motor plasticity induced by intermittent hypoxia is suppressed by lipopolysaccharide (LPS) induced inflammation (Vinit et al, 2011). Similarly, injury-induced inflammation may at least transiently impair plasticity following cervical spinal injury.…”

Section: Discussionmentioning

confidence: 99%

Glial activation in the spinal ventral horn caudal to cervical injury

Windelborn

Mitchell

2012

Respiratory Physiology & Neurobiology

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Microglia and astrocytes play complex roles following spinal cord injury (SCI), contributing to inflammatory processes that both exacerbate injury and promote functional recovery by supporting neuro-protection and neuroplasticity. The crossed phrenic phenomenon (CPP) is an example of respiratory plasticity in which C2 cervical hemisection (C2HS) strengthens crossed-spinal synaptic pathways to phrenic motor neurons ipsilateral to injury. We hypothesized that microglia and astrocytes are activated in the phrenic motor nucleus caudal and ipsilateral to C2HS, suggesting their potential for involvement in the CPP. To test this hypothesis, an incomplete cervical spinal hemisection (C2 lateral injury; C2LI) was performed, and rats were allowed to recover for 1, 3, 14 or 28 days before collecting perfused spinal tissues. Microglia (via OX42) and astrocytes (via GFAP) were visualized with immunofluorescence microscopy in the C4-C5 ventral horn, the region encompassing most of the phrenic motor nucleus. OX42-occupied fractional area ipsilateral to injury increased with C2LI (vs. sham) at 1 (12.5 +/- 1.8%, p<0.001), 3 (29.0 +/- 1.9%, p<0.001), 14 (26.1 +/- 3.1%, p<0.001) and 28 (19.2 +/- 2.0%, p<0.001) days post-C2LI. GFAP-occupied fractional area also increased with C2LI at 3 (24.4 +/- 3.2%, p<0.001) and 14 (16.8 +/- 8.3%, p=0.012) days, but not at 1 (6.2 +/- 3.9%, p=0.262) or 28 (10.6 +/- 3.9%, p=0.059) days post-C2LI. Thus, microglia and astrocytes are activated in the phrenic motor nucleus caudal to C2LI, suggesting that they play a role in functional deficits and/or recovery following spinal injury.

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Lipopolysaccharide attenuates phrenic long-term facilitation following acute intermittent hypoxia

Cited by 60 publications

References 34 publications

Respiratory function after selective respiratory motor neuron death from intrapleural CTB–saporin injections

Respiratory function after selective respiratory motor neuron death from intrapleural CTB–saporin injections

A Murine Model of Cervical Spinal Cord Injury to Study Post-lesional Respiratory Neuroplasticity

Glial activation in the spinal ventral horn caudal to cervical injury

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