RESUMEN
Bronchoscopy has garnered increased popularity in the biopsy of peripheral lung lesions. The development of navigational guided bronchoscopy systems along with radial endobronchial ultrasound (REBUS) allows clinicians to access and sample peripheral lesions. The development of robotic bronchoscopy improved localization of targets and diagnostic accuracy. Despite such technological advancements, published diagnostic yield remains lower compared to computer tomography (CT)-guided biopsy. The discordance between the real-time location of peripheral lesions and anticipated location from preplanned navigation software is often cited as the main variable impacting accurate biopsies. The utilization of cone beam CT (CBCT) with navigation-based bronchoscopy has been shown to assist with localizing targets in real-time and improving biopsy success. The resources, costs, and radiation associated with CBCT remains a hindrance in its wider adoption. Recently, digital tomosynthesis (DT) platforms have been developed as an alternative for real-time imaging guidance in peripheral lung lesions. In North America, there are several commercial platforms with distinct features and adaptation of DT. Early studies show the potential improvement in peripheral lesion sampling with DT. Despite the results of early observational studies, the true impact of DT-based imaging devices for peripheral lesion sampling cannot be determined without further prospective randomized trials and meta-analyses.
RESUMEN
Injury to the supraspinal motor systems, especially the corticospinal tract, leads to movement impairments. In addition to direct disruption of descending motor pathways, spinal motor circuits that are distant to and not directly damaged by the lesion undergo remodeling that contributes significantly to the impairments. Knowing which spinal circuits are remodeled and the underlying mechanisms are critical for understanding the functional changes in the motor pathway and for developing repair strategies. Here, we target spinal premotor cholinergic interneurons (IN) that directly modulate motoneuron excitability via their cholinergic C-bouton terminals. Using a model of unilateral medullary corticospinal tract lesion in male rats, we found transneuronal downregulation of the premotor cholinergic pathway. Phagocytic microglial cells were upregulated in parallel with cholinergic pathway downregulation and both were blocked by minocycline, a microglia activation inhibitor. Additionally, we found a transient increase in interneuronal complement protein C1q expression that preceded cell loss. 3D reconstructions showed ongoing phagocytosis of C1q-expressing cholinergic INs by microglia 3 d after injury, which was complete by 10 d after injury. Unilateral motor cortex inactivation using the GABAA receptor agonist muscimol replicated the changes detected at 3 d after lesion, indicating activity dependence. The neuronal loss after the lesion was rescued by increasing spinal activity using cathodal trans-spinal direct current stimulation. Our finding of activity-dependent modulation of cholinergic premotor INs after CST injury provides the mechanistic insight that maintaining activity, possibly during a critical period, helps to protect distant motor circuits from further damage and, as a result, may improve motor functional recovery and rehabilitation.SIGNIFICANCE STATEMENT Supraspinal injury to the motor system disrupts descending motor pathways, leading to movement impairments. Whether and how intrinsic spinal circuits are remodeled after a brain injury is unclear. Using a rat model of unilateral corticospinal tract lesion in the medulla, we show activity-dependent, transneuronal downregulation of the spinal premotor cholinergic system, which is mediated by microglial phagocytosis, possibly involving a rapid and transient increase in neuronal C1q before neuronal loss. Spinal cord neuromodulation after injury to augment spinal activity rescued the premotor cholinergic system. Our findings provide the mechanistic insight that maintaining activity, possibly during an early critical period, could protect distant motor circuits from further damage mediated by microglia and interneuronal complement protein and improve motor functional outcomes.
