Midcervical contusion injuries disrupt descending ipsilateral excitatory bulbospinal projections to phrenic motoneurons, compromising ventilation. We hypothesized that a unilateral contusion injury at C3 versus C5 would differentially impact phrenic activity reflecting more prominent disruption of ipsilateral descending excitatory drive to more caudal segments of the phrenic motor pool with more cranial injuries. Phrenic motoneuron counts and evidence of diaphragm muscle denervation at individual neuromuscular junctions (NMJ) were evaluated at 14 days post-injury after unilateral contusion injury (100 kDynes). Whole body plethysmography and chronic diaphragm EMG were measured before the injury and at 3, 7, and 14 days post-injury. Contusion injuries at either level resulted in a similarly sized cavity. C3 contusion resulted in loss of 39 ± 13% of ipsilateral phrenic motoneurons compared with 13 ± 21% after C5 contusion (p = 0.003). Cervical contusion injuries resulted in diaphragm muscle denervation (C3 contusion: 17 ± 4%; C5 contusion: 7 ± 4%; p = 0.047). The pattern of denervation revealed segmental innervation of the diaphragm muscle, with greater denervation ventrally after C3 contusion and dorsally after C5 contusion. Overall, diaphragm root mean square electromyography activity did not change ipsilaterally after C3 or C5 contusion, but increased contralaterally (∼ 11%) after C3 contusion only on the first day post-injury (p = 0.026). Similarly, there were no significant changes in breathing parameters during eupnea or exposure to hypoxia (10% O2) - hypercapnia (5% CO2) at any time post-injury. Unilateral midcervical contusions minimally impair ventilatory behaviors despite phrenic motoneuron loss and diaphragm muscle denervation.

Macrophages were first described as phagocytic immune cells responsible for maintaining tissue homeostasis by the removal of pathogens that disturb normal function. Historically, macrophages have been viewed as terminally differentiated monocyte-derived cells that originated through hematopoiesis and infiltrated multiple tissues in the presence of inflammation or during turnover in normal homeostasis. However, improved cell detection and fate-mapping strategies have elucidated the various lineages of tissue-resident macrophages, which can derive from embryonic origins independent of hematopoiesis and monocyte infiltration. The role of resident macrophages in organs such as the skin, liver, and the lungs have been well characterized, revealing functions well beyond a pure phagocytic and immunological role. In the heart, recent research has begun to decipher the functional roles of various tissue-resident macrophage populations through fate mapping and genetic depletion studies. Several of these studies have elucidated the novel and unexpected roles of cardiac-resident macrophages in homeostasis, including maintaining mitochondrial function, facilitating cardiac conduction, coronary development, and lymphangiogenesis, among others. Additionally, following cardiac injury, cardiac-resident macrophages adopt diverse functions such as the clearance of necrotic and apoptotic cells and debris, a reduction in the inflammatory monocyte infiltration, promotion of angiogenesis, amelioration of inflammation, and hypertrophy in the remaining myocardium, overall limiting damage extension. The present review discusses the origin, development, characterization, and function of cardiac macrophages in homeostasis, cardiac regeneration, and after cardiac injury or stress.

Infants born very prematurely (<28 weeks gestation) have immature lungs and often require supplemental oxygen. However, long‐term hyperoxia exposure can arrest lung development leading to bronchopulmonary dysplasia (BPD), which increases acute and long‐term respiratory morbidity and mortality. The neural mechanisms controlling breathing are highly plastic during development. Whether the ventilatory control system adapts to pulmonary disease associated with hyperoxia exposure in infancy remains unclear. Here, we tested the hypothesis that there would be age‐dependent adaptations in the control of breathing in an established rat model of hyperoxia‐induced BPD. Hyperoxia exposure (FIO2: 0.9 from 0–10 days of life) led to a BPD‐like lung phenotype, including sustained reductions in alveolar surface area and counts, and modest increases in airway resistance. Hyperoxia exposure also led to chronic increases in room air and acute hypoxic minute ventilation (VE) and age‐dependent changes in breath‐to‐breath tidal volume and breathing frequency variability. Hyperoxia‐exposed rats had normal hypoxic ventilatory responses, oxygen saturation (SpO2) in room air, but greater reductions in SpO2 during acute hypoxia (12% O2) indicating reduced hypoxic sensitivity and/or hypoventilation due to diseased lungs. However, VE was increased indicating an increase in respiratory drive. Perinatal hyperoxia led to greater glial fibrillary acidic protein expression and an increase in neuron counts within 6 of 8 and 1 of 8 key brainstem regions controlling breathing, respectively, suggesting astrocytic expansion. In conclusion, perinatal hyperoxia in rats induced a BPD‐like phenotype and age‐dependent adaptations in VE that may be mediated through changes to the neural architecture of the ventilatory control system. Our results suggest chronically altered ventilatory control in BPD. Support or Funding Information Children's Research Hospital of Wisconsin Research Institute, NIH R01 HL 122358, & Parker B. Francis Foundation This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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