Carotid bodies mediate glial cell activation and neuroinflammation in the NTS following long-term intermittent hypoxia: role in cardiorespiratory dysfunction.

Chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea, heightened chemosensory discharges of the carotid body (CB), which contributes to potentiate the ventilatory hypoxic response and elicits hypertension. We aimed to determine: 1) whether the persistence of cardiorespiratory alterations found in long-term CIH depend on the inputs from the CB and, 2) in what extension the activation of glial cells and neuroinflammation in the caudal region of the nucleus of the Solitary Tract (NTS) requires functional CB chemosensory activity. To evaluate these hypotheses, we exposed male mice to CIH for 60 days. At 50 days of CIH, CBs were denervated and animals were kept in CIH for 10 additional days. At the end of the experiments, we measured arterial blood pressure, breathing regularity, and hypoxic ventilatory response (HVR) and assessed astrocyte and microglia cell activation. Compared to Sham, CIH induces hypertension (MABP: 83.47±1.39 vs. 95.00±2.18 mmHg), disordered breathing (IS: 7.77±0.49 vs. 12.56±1.66), increased the HVR (1.69±0.17 vs. 4.31±0.87 ΔV_E/min), and produced an early transient activation of astrocytes followed by a late and persistent activation of microglia in the NTS. In addition, CIH increased IL-1β, IL-6, and TNF-α levels in the NTS. Bilateral CB denervation after 50 days of CIH results in the restoration of normal glial cell activation in the NTS, lower levels of IL-6 and TNF-α, reductions in arterial blood pressure (83.47±1.38 mmHg) and HVR (1.63±0.43 ΔV_E/min). Present results suggest that CB inputs to the NTS during long-term CIH contributes to maintain the cardiorespiratory alterations and the formation of a neuroinflammatory niche at the NTS by modifying glial cell activity.