Respiratory physiology & neurobiology
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Respir Physiol Neurobiol · Dec 2009
Role of cholinergic-nicotinic receptors on hypoxic chemoreflex during postnatal development in rats.
We tested the hypothesis that the function of cholinergic-nicotinic receptors on respiration is age dependent. To this end, we used whole body plethysmography to measure breathing frequency (fR), tidal volume (V(T)) and minute ventilation (V (E)) under normoxia (21% O(2)) in rats at 1, 4, 7, 12 and 21 postnatal days before and after administration of epibatidine (nicotinic agonist 5 microg/kg, i.p.). In normoxia, epibatidine increased fR and V (E) in a proportionally age-dependent manner (p for age <0.001), without affecting V(T). ⋯ In P12 rats, in vitro recordings of carotid sinus nerve activity showed that superfusion with nicotine enhanced chemosensory discharge rate in normoxia and hexamethonium reduced the discharge rate in hypoxia. We also identified the nicotinic receptor alpha7 subunit by immunohistochemistry in carotid bodies from P12 rat. These data show that the role of cholinergic-nicotinic receptor on hypoxic chemoreflex is age dependent and this effect likely implicates carotid body nicotinic receptor activation.
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Respir Physiol Neurobiol · Jun 2012
Anti-inflammatory and neuroprotective effects of triptolide on traumatic brain injury in rats.
Traumatic brain injury (TBI) is characterized by neuroinflammation, brain edema, and cerebral damage leading to impairment of neurobehavioral function. Triptolide (PG-490), a diterpenoid component from Tripterygium wilfordii Hook F., has anti-inflammatory properties. Whether triptolide has neuroprotective functions when treating TBI is unclear. ⋯ Thriptolide reversed the TBI-induced decrease in brain levels of anti-inflammatory cytokine interleukin-10. Importantly, triptolide improved neurobehavioral outcomes regarding motor, sensory, reflex and balance function. We conclude that triptolide confers neuroprotection against TBI, at least in part, via its anti-inflammatory activity.
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Respir Physiol Neurobiol · Jul 2010
Methylxanthine reversal of opioid-evoked inspiratory depression via phosphodiesterase-4 blockade.
Hypothetic mechanisms for respirogenic methylxanthine actions include blockade of adenosine receptors or phosphodiesterase-4 (PDE4) in inspiratory pre-Bötzinger complex (preBötC) networks. Here, we studied this by analyzing stimulating caffeine and theophylline actions on mu-opioid-depressed inspiratory-related rhythm in the ventrolateral aspect of rat brainstem slices. The methylxanthines restored DAMGO (0.5-1 microM) depressed rhythm only at >1mM, which is approximately 10-fold higher than selective for adenosine receptors. ⋯ At 0.25 microM, rolipram boosted incomplete recovery by 1 mM theophylline of DAMGO-depressed rhythm. Findings indicate that methylxanthines excite rhythmogenic preBötC networks via blockade of cAMP dependent PDE4 and suggest that specific PDE4 inhibitors (plus low methylxanthine doses) stimulate breathing effectively. We discuss why methylxanthine doses for preBötC stimulation need to be higher than those for respirogenic effects in vivo.
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Respir Physiol Neurobiol · Dec 2009
Lung volume recruitment maneuvers and respiratory system mechanics in mechanically ventilated mice.
The study aim was to establish how recruitment maneuvers (RMs) influence lung mechanics and to determine whether RMs produce lung injury. Healthy BALB/c mice were allocated to receive positive end-expiratory pressure (PEEP) at 2 or 6 cmH(2)O and volume- (20 or 40 mL/kg) or pressure-controlled (25 cmH(2)O) RMs every 5 or 75 min for 150 min. ⋯ Large RMs resulting in peak airway opening pressures (P(ao))>30 cmH(2)O did not increase inflammatory response or affect transcutaneous oxygen saturation but significantly lowered airway resistance, tissue damping and tissue elastance; the latter changes are likely associated with the bimodal pressure-volume behavior observed in mice. PEEP increase alone and application of RMs producing peak P(ao) below 25 cmH(2)O did not prevent or reverse changes in lung mechanics; whereas frequent application of substantial RMs on top of elevated PEEP levels produced stable lung mechanics without signs of lung injury.
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Respir Physiol Neurobiol · Aug 2011
Alteration of carotid body chemoreflexes after neonatal intermittent hypoxia and caffeine treatment in rat pups.
In human neonates, caffeine therapy for apnoea of prematurity, especially when associated with hypoxemia, is maintained for several weeks after birth. In the present study, we used newborn rats and whole-body plethysmography to test whether chronic exposure to neonatal caffeine treatment (NCT), alone or combined with neonatal intermittent hypoxia (n-IH) alters: (1) baseline ventilation and response to hypoxia (12% O(2), 20 min); and (2) response to acute i.p. injection of caffeine citrate (20 mg/kg) or domperidone, a peripheral dopamine D2 receptor antagonist (1 mg/kg). Four groups of rats were studied as follows: raised under normal conditions with daily gavage with water (NWT) or NCT, or exposed to n-IH (n-IH+NWT and n-IH+NCT) from postnatal days 3 to 12. ⋯ During the late response phase to hypoxia (20 min), ventilation was lower in n-IH+NWT and n-IH+NCT rats compared to NWT or NCT, and were not affected by caffeine or domperidone injection. NCT or caffeine injection decreased baseline apnoea frequency in all groups. These data suggest that chronic exposure to NCT alters both carotid body dopaminergic and adenosinergic systems and central regulation of breathing under baseline conditions and in response to hypoxia.