Peripheral-to-central immune communication at the area postrema glial-barrier following bleomycin-induced sterile lung injury in adult rats

Litvin, David; Denstaedt, Scott J.; Borkowski, Lauren F.; Nichols, Nicole L.; Smith, Corey; Jacono, Frank J.

doi:10.1016/j.bbi.2020.02.006

Cited by 18 publications

(12 citation statements)

References 330 publications

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“…Bilateral micro-injections of IL-1β in the NTS of naïve rats showed increased f R similar to that found in rats with ALI. They speculated that though initiated by sensory input, the characteristic ventilatory pattern after lung injury may be mediated by neuro-inflammation by cytokines in the NTS ( Getsy et al, 2019 ; Hsieh et al, 2020 ; Litvin et al, 2020 ). Based on their evidence, it would not be surprising to expect similar plasticity in the NTS during the recovery stages of ALI.…”

Section: Discussionmentioning

confidence: 99%

Time-dependent alteration in the chemoreflex post-acute lung injury

Kamra

Karpuk²,

Adam³

et al. 2022

Front. Physiol.

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Acute lung injury (ALI) induces inflammation that disrupts the normal alveolar-capillary endothelial barrier which impairs gas exchange to induce hypoxemia that reflexively increases respiration. The neural mechanisms underlying the respiratory dysfunction during ALI are not fully understood. The purpose of this study was to investigate the role of the chemoreflex in mediating abnormal ventilation during acute (early) and recovery (late) stages of ALI. We hypothesized that the increase in respiratory rate (fR) during post-ALI is mediated by a sensitized chemoreflex. ALI was induced in male Sprague-Dawley rats using a single intra-tracheal injection of bleomycin (Bleo: low-dose = 1.25 mg/Kg or high-dose = 2.5 mg/Kg) (day 1) and respiratory variables- fR, Vt (Tidal Volume), and VE (Minute Ventilation) in response to 10% hypoxia (10% O2, 0% CO2) and 5% hypercapnia/21% normoxia (21% O2, 5% CO2) were measured weekly from W0-W4 using whole-body plethysmography (WBP). Our data indicate sensitization (∆fR = 93 ± 31 bpm, p < 0.0001) of the chemoreflex at W1 post-ALI in response to hypoxic/hypercapnic gas challenge in the low-dose bleo (moderate ALI) group and a blunted chemoreflex (∆fR = −0.97 ± 42 bpm, p < 0.0001) at W1 post-ALI in the high-dose bleo (severe ALI) group. During recovery from ALI, at W3-W4, both low-dose and high-dose groups exhibited a sensitized chemoreflex in response to hypoxia and normoxic-hypercapnia. We then hypothesized that the blunted chemoreflex at W1 post-ALI in the high-dose bleo group could be due to near maximal tonic activation of chemoreceptors, called the “ceiling effect”. To test this possibility, 90% hyperoxia (90% O2, 0% CO2) was given to bleo treated rats to inhibit the chemoreflex. Our results showed no changes in fR, suggesting absence of the tonic chemoreflex activation in response to hypoxia at W1 post-ALI. These data suggest that during the acute stage of moderate (low-dose bleo) and severe (high-dose bleo) ALI, chemoreflex activity trends to be slightly sensitized and blunted, respectively while it becomes significantly sensitized during the recovery stage. Future studies are required to examine the molecular/cellular mechanisms underlying the time-course changes in chemoreflex sensitivity post-ALI.

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Section: Discussionmentioning

confidence: 99%

Time-dependent alteration in the chemoreflex post-acute lung injury

Kamra

Karpuk²,

Adam³

et al. 2022

Front. Physiol.

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“…Various disease models with short temporal activation of the immune system, such as bleomycininduced lung injury and dextran sulfate sodium induced colitis (26,27), suggest that activation of microglia in the sCVOs accompanies in ammatory symptoms, but only for a limited period. Acute systemic injection of IL-1β, TNF-α, and lipopolysaccharide (LPS) increase c-Fos expression in the AP within a short latency and duration (19,(45)(46)(47).…”

Section: Discussionmentioning

confidence: 99%

“…Morphologically activated microglia are characterized by an ameboid-shape with a swollen cell body (22), and also by expression and release of in ammatory cytokines (23) that can modulate neuronal activity (24), which suggests their morpho-functional coactivation (25). It is likely that microglia in the sCVOs play a role in mediating peripheral in ammation and neuronal activity in the brain, as shown in various in ammatory disease models, such as bleomycin-induced lung injury and dextran sulfate sodium induced colitis (26,27). We therefore determined whether microglia in sCVOs are morpho-functionally activated in collagen-induced arthritis (CIA) mice, a model for RA with autoimmune arthritis and increased levels of systemic in ammatory mediators (28) that can activate microglia cells (29)(30)(31).…”

mentioning

confidence: 99%

Sustained Microglial Activation in the Area Postrema of Collagen-induced Arthritis Mice: a Potential Pathway Linking Arthritis and the Brain

Matsushita

Otani

Oto

et al. 2021

Preprint

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Background. Neuropsychological symptoms are common complications among patients with rheumatoid arthritis (RA), while it is largely unexplored how RA pathology spread to brain protected by blood-brain barrier (BBB). The sensory circumventricular organs (sCVOs) (brain regions lacking a blood–brain barrier) is the brain site that peripheral inflammatory signals, such as blood cytokines and chemokines, can directly access and modulate cell activities in the brain parenchyma. To determine whether microglia, resident immune cells in neuronal tissue, in the sCVOs can function as an interface between peripheral inflammation and brain under the autoimmune-arthritis conditions, we analyzed microglia in the sCVOs of a mouse model of collagen-induced arthritis (CIA).Methods. Microglial number and morphology were analyzed in the sCVOs of CIA and control mice (controls were administrated Freund’s adjuvant [FA] and/or saline). Immunostaining for ionized calcium-binding adaptor molecule-1 was performed at various disease phases: “pre-onset” (post-immunization day [PID] 21), ”establishment” (PID 35), and “chronic” (PID 56 and 84). Quantitative analyses on microglial number and morphology were performed, with principal component analysis used to classify microglia. Interleukin-1β (IL-1β) mRNA expression in microglia was also analyzed by multiple fluorescent in situ hybridization.Results. In the area postrema (AP), one of the sCVOs located in the medulla, microglia significantly increased in density (CIA, n = 15; FA, n = 6; saline: n = 10) with changes in morphology during the establishment and chronic phases. In other sCVOs (subfornical organs [SFO] and organum vasculosum laminae terminalis [OVLT]), microglial changes were not significant. In the AP microglia, non-subjective clustering classification of cell morphology (CIA, 1,256 cells; saline, 852 cells) showed that the proportion of microglia in a highly activated form was increased in the CIA group. Also, the density of IL-1β-positive microglia, a hallmark of functional activation, increased in the AP. These microglial changes in the AP persisted until the chronic phase.Conclusions. Our findings indicate that an increase and activation of microglia is sustained in the AP during chronic arthritis. This suggests that there is a direct physiological pathway linking peripheral arthritis to the brain through the AP.

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“…It is therefore legitimate to focus on these cells as a priority when we want to identify neuroglial interactions within DVC. The simple detection of the emblematic marker of astrocytes, glial fibrillary acidic protein (GFAP), has revealed a striking pattern of GFAP immunoreactivity in DVC, which distinguishes it from the surrounding brainstem nuclei, i.e., the hypoglossal nucleus, dorsal tegmentum, and medullary reticular nucleus ( [21][22][23] and Figure 2). While NTS and DMNX appear heavily labeled throughout their entire rostrocaudal extent, weak GFAP labelling is observed in AP [22].…”

Section: Cellular Diversity and Glial Organization Within The Adult Dvcmentioning

confidence: 99%

Glial Modulation of Energy Balance: The Dorsal Vagal Complex Is No Exception

Troadec

Gaigé

Barbot

et al. 2022

IJMS

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The avoidance of being overweight or obese is a daily challenge for a growing number of people. The growing proportion of people suffering from a nutritional imbalance in many parts of the world exemplifies this challenge and emphasizes the need for a better understanding of the mechanisms that regulate nutritional balance. Until recently, research on the central regulation of food intake primarily focused on neuronal signaling, with little attention paid to the role of glial cells. Over the last few decades, our understanding of glial cells has changed dramatically. These cells are increasingly regarded as important neuronal partners, contributing not just to cerebral homeostasis, but also to cerebral signaling. Our understanding of the central regulation of energy balance is part of this (r)evolution. Evidence is accumulating that glial cells play a dynamic role in the modulation of energy balance. In the present review, we summarize recent data indicating that the multifaceted glial compartment of the brainstem dorsal vagal complex (DVC) should be considered in research aimed at identifying feeding-related processes operating at this level.

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Peripheral-to-central immune communication at the area postrema glial-barrier following bleomycin-induced sterile lung injury in adult rats

Cited by 18 publications

References 330 publications

Time-dependent alteration in the chemoreflex post-acute lung injury

Time-dependent alteration in the chemoreflex post-acute lung injury

Sustained Microglial Activation in the Area Postrema of Collagen-induced Arthritis Mice: a Potential Pathway Linking Arthritis and the Brain

Glial Modulation of Energy Balance: The Dorsal Vagal Complex Is No Exception

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