Differential Effects of Systemic versus Intratracheal Lipopolysaccharide (LPS) Administration on Ventilatory Behavior in Spontaneously Breathing Adult C57BL/6 Male Mice

Abstract

Both intraperitoneal (ip; systemic) and intratracheal (IT) administration of the bacterial endotoxin LPS have been used to elicit neuroinflammation. While both methods are reported to induce time‐dependent changes in expression levels of pro‐inflammatory cytokines in the CNS, their effects on basal ventilatory activity remain to be characterized. Here, we report the ventilatory behavior (recorded using whole body plethysmography) before and after administration of LPS delivered either ip (5 mg/kg) or IT (0.5 mg/kg) in unanesthetized spontaneously breathing adult C57BL/6 male mice. Before LPS, ventilatory activity consisted of a fairly regular pattern of breathing, which included periodic short duration apneic pauses (as previously described in this strain) and occasional sighs. Both ip and IT LPS altered ventilatory activity; however, the effects were not identical. IP LPS (1) robustly increased breathing frequency and progressively decreased tidal volume and (2) reduced or eliminated the incidence of both apneic pauses and sighs. IT LPS (1) increased breathing frequency and progressively decreased tidal volume, but to a lesser extent than ip, (2) produced periods of dysrhythmic breathing, (3) prolonged the durations of the apneic pauses; and (4) increased the incidence of sighs. These findings indicate that while both methods of administration alter ventilatory activity, the resulting ventilatory patterns are markedly different. We suggest that differences in the extent of ip versus IT LPS‐induced neuroinflammatory changes in respiratory‐related brainstem and spinal cord regions mediate, at least in part, these different ventilatory behaviors.