Astrocyte immunosenescence in IL-10 and cholesterol signaling in the aged brain impairs microglial regulation following peripheral immune activation

The diaphragm muscle (DIAm) has a large reserve capacity for force generation such that in rats, the transdiaphragmatic pressure (Pdi) generated during ventilatory behaviors is less than 50% of maximal Pdi (Pdimax) elicited by bilateral phrenic nerve stimulation. Accordingly, we hypothesized that following unilateral denervation (DNV), the ability of the contralateral DIAm to generate sufficient Pdi to accomplish ventilatory behaviors will not be compromised and normal ventilation (as determined by arterial blood gas measurements) will not be impacted, although neural drive to the DIAm increases. In contrast, we hypothesized that higher force, non-ventilatory behaviors requiring Pdi generation greater than 50% of Pdimax will be compromised following DIAm hemiparalysis, i.e., increased neural drive cannot fully compensate for lack of force generating capacity. Pdi generated during ventilatory behaviors (eupnea and hypoxia (10% O2)–hypercapnia (5% CO2)) did not change after DNV and arterial blood gases were unaffected by DNV. However, neural drive to the contralateral DIAm, assessed by the rate of rise of root mean squared (RMS) EMG at 75 ms after onset of inspiratory activity (RMS75), increased after DNV (p < 0.05). In contrast, Pdi generated during higher force, non-ventilatory behaviors was significantly reduced after DNV (p < 0.01), while RMS75 was unchanged. These findings support our hypothesis that only non-ventilatory behaviors requiring Pdi generation greater than 50% of Pdimax are impacted after DNV. Clinically, these results indicate that an evaluation of DIAm weakness requires examination of Pdi across multiple motor behaviors, not just ventilation.