Microglia modulate respiratory rhythm generation and autoresuscitation

Abstract

Inflammation has been linked to the induction of apneas and Sudden Infant Death Syndrome, whereas proinflammatory mediators inhibit breathing when applied peripherally or directly into the CNS. Considering that peripheral inflammation can activate microglia in the CNS and that this cell type can directly release all proinflammatory mediators that modulate breathing, it is likely that microglia can modulate breathing generation. It might do so also in hypoxia, since microglia are sensitive to hypoxia, and peripheral proinflammatory conditions affect gasping generation and autoresuscitation. Here, we tested whether microglial activation or inhibition affected respiratory rhythm generation. By measuring breathing as well as the activity of the respiratory rhythm generator (the preBötzinger complex), we found that several microglial activators or inhibitors, applied intracisternally in vivo or in the recording bath in vitro, affect the generation of the respiratory rhythms both in normoxia and hypoxia. Furthermore, microglial activation with lipopolysaccharide affected the ability of the animals to autoresuscitate after hypoxic conditions, an effect that is blocked when lipopolysaccharide is co-applied with the microglial inhibitor minocycline. Moreover, we found that the modulation of respiratory rhythm generation induced in vitro by microglial inhibitors was reproduced by microglial depletion. In conclusion, our data show that microglia can modulate respiratory rhythm generation and autoresuscitation.

Neuroimmune modulation of cardiorespiratory responses to acute severe hypoxia

“…() was a finding of blunted ventilation during hypoxia in minocycline‐treated rats compared with vehicle‐treated control animals, whereas normoxic ventilation was unaffected by minocycline treatment. The suppression of hypoxic ventilation is consistent with recent observations that microglial inactivation blunts time‐dependent ventilatory responses to hypoxia (Lorea‐Hernández, Morales, Rivera‐Angulo, Alcantara‐Gonzalez, & Peña‐Ortega, ; Stokes, Arbogast, Moya, Fu, & Powell, ; Tadmouri, Champagnat, & Morin‐Surun, ). The observation of Silva et al.…”

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

“…Minocycline also attenuated the hypoxia ventilatory response. Our findings are in agreement with the literature, indicating that microglia inhibition affects breathing activity, since intracisternal injection of minocycline reduces the hypoxia ventilatory response (Lorea‐Hernandez, Morales, Rivera‐Angulo, Alcantara‐Gonzalez, & Pena‐Ortega, ). In addition, minocycline was also able to decrease the ventilatory acclimatization of 24 h under hypoxia, due to blockade of the continuous increase in tidal volume (Tadmouri, Champagnat, & Morin‐Surun, ).…”

Advances in cellular and integrative control of oxygen homeostasis within the central nervous system

“…; Lorea‐Hernandez et al . ; Peña‐Ortega, ). Hypoxia evokes a biphasic response: a rapid augmentation with the generation of sighs is followed by a respiratory depression (Fig.…”