Time Course of Altered Ventilatory Activity Evoked by Systemic Lipopolysaccharide (LPS) Administration in Spontaneously Breathing Adult C57BL/6 Male Mice

Abstract

Systemic administration of the bacterial endotoxin lipopolysaccharide (LPS) is commonly used to study inflammation‐associated behavioral and biochemical changes in rodents that are attributed to neuroinflammation. Little is known, however, about the time course of alterations in ventilatory activity following systemic LPS administration. Therefore, the present study was designed to evaluate the effects of a single bolus of high dose LPS (5 mg/kg, ip) or vehicle (saline) on basal ventilatory behavior (recorded using whole body plethysmography) in unanesthetized spontaneously breathing adult C57BL/6 male mice at 2‐, 6‐, and 24‐hr post administration. Before LPS, ventilatory activity was characterized by a regular pattern of breathing that included spontaneous apneic pauses (which have been previously described in this strain) and periodic sighs. A similar ventilatory pattern was seen following saline administration. After LPS, changes in ventilatory activity were noted as early as 2‐hr, with the primary changes consisting of: (1) an increase in breathing frequency of up to 50% above pre‐LPS levels at 2‐hr post‐LPS, after which a progressive attenuation of the frequency increase to 蠄25% was noted; (2) a decrease in the incidence of apneic pauses and sighs by 2‐hr post‐LPS, after which both ventilatory behaviors were further reduced or eliminated; and (3) a progressive decrease in tidal volume. These findings indicate that systemic LPS administration produces time‐dependent modulation of ventilatory activity, which we propose results from the time‐dependent LPS‐induced changes in cytokine expression in respiratory‐related brainstem and spinal cord regions.