Preterm infants are at risk for a broad spectrum of neurobehavioral disabilities associated with diffuse disturbances in cortical growth and development. During brain development, subplate neurons (SPNs) are a largely transient population that serves a critical role to establish functional cortical circuits. By dynamically integrating into developing cortical circuits, they assist in consolidation of intracortical and extracortical circuits. Although SPNs reside in close proximity to cerebral white matter, which is particularly vulnerable to oxidative stress, the susceptibility of SPNs remains controversial. We determined SPN responses to two common insults to the preterm brain: hypoxia-ischemia and hypoxia. We used a preterm fetal sheep model using both sexes that reproduces the spectrum of human cerebral injury and abnormal cortical growth. Unlike oligodendrocyte progenitors, SPNs displayed pronounced resistance to early or delayed cell death from hypoxia or hypoxia-ischemia. We thus explored an alternative hypothesis that these insults alter the maturational trajectory of SPNs. We used DiOlistic labeling to visualize the dendrites of SPNs selectively labeled for complexin-3. SPNs displayed reduced basal dendritic arbor complexity that was accompanied by chronic disturbances in SPN excitability and synaptic activity. SPN dysmaturation was significantly associated with the level of fetal hypoxemia and metabolic stress. Hence, despite the resistance of SPNs to insults that trigger white matter injury, transient hypoxemia disrupted SPN arborization and functional maturation during a critical window in cortical development. Strategies directed at limiting the duration or severity of hypoxemia during brain development may mitigate disturbances in cerebral growth and maturation related to SPN dysmaturation. The human preterm brain commonly sustains blood flow and oxygenation disturbances that impair cerebral cortex growth and cause life-long cognitive and learning disabilities. We investigated the fate of subplate neurons (SPNs), which are a master regulator of brain development that plays critical roles in establishing cortical connections to other brain regions. We used a preterm fetal sheep model that reproduces key features of brain injury in human preterm survivors. We analyzed the responses of fetal SPNs to transient disturbances in fetal oxygenation. We discovered that SPNs are surprisingly resistant to cell death from low oxygen states but acquire chronic structural and functional changes that suggest new strategies to prevent learning problems in children and adults that survive preterm birth.
Children who survive premature birth often exhibit reductions in hippocampal volumes and deficits in working memory. However, it is unclear whether synaptic plasticity and cellular mechanisms of learning and memory can be elicited or disrupted in the preterm fetal hippocampus. CA1 hippocampal neurons were exposed to two common insults to preterm brain: transient hypoxia-ischemia (HI) and hypoxia (Hx). We used a preterm fetal sheep model using both sexes in twin 0.65 gestation fetuses that reproduces the spectrum of injury and abnormal growth in preterm infants. Using Cavalieri measurements, hippocampal volumes were reduced in both Hx and HI fetuses compared with controls. This volume loss was not the result of neuronal cell death. Instead, morphometrics revealed alterations in both basal and apical dendritic arborization that were significantly associated with the level of systemic hypoxemia and metabolic stress regardless of etiology. Anatomical alterations of CA1 neurons were accompanied by reductions in probability of presynaptic glutamate release, long-term synaptic plasticity and intrinsic excitability. The reduction in intrinsic excitability was in part due to increased activity of the channels underlying the fast and slow component of the afterhyperpolarization in Hx and HI. Our studies suggest that even a single brief episode of hypoxemia can markedly disrupt hippocampal maturation. Hypoxemia may contribute to long-term working memory disturbances in preterm survivors by disrupting neuronal maturation with resultant functional disturbances in hippocampal action potential throughput. Strategies directed at limiting the duration or severity of hypoxemia during brain development may mitigate disturbances in hippocampal maturation.
Background It is common practice to use a combination approach of computed tomography (CT) scan followed by upright radiographs when assessing traumatic thoracolumbar (TL) vertebral fractures. The purpose of this study was to determine the clinical utility of upright spine radiographs in the setting of traumatic TL fracture management. Our null hypothesis is that upright TL radiographs rarely change management of acute vertebral fractures. Methods A retrospective study was performed on patients with an initial plan of non-operative management for a TL fracture between January 2014 and June 2020 at a single Level 1 trauma center. Patients were followed from time of initial consult to either conversion to surgery (operative) or last available outpatient follow up imaging (non-operative). Lateral kyphotic angle of the fractured vertebra and anterior vertebral body height% loss on initial CT, first upright radiograph, and endpoint upright radiograph imaging were measured. Measurements were compared between and within operative and non-operative groups using t-tests and Mann-Whitney U tests when appropriate. P-values ≤ 0.05 were considered statistically significant. Results The study included 70 patients with an average age of 54 years and 37 (52.9%) were women. Six (8.6%) of 70 patients had a change from non-operative to operative management based on upright radiographs. The mean (standard deviation) change in degrees of kyphosis from CT scan to first X-ray was 4.6 (7.0) in the non-operative group and 11.5 (8.1) in the operative group (P = 0.03). Delta degrees of kyphosis from CT scan to endpoint X-ray was 6.4 (9.0) and 16.2 (6.2) in the non-operative and operative groups, respectively (P = 0.01). In the operative group, mean degrees of kyphosis increased from 1.6 (7.6) in initial CT to 13.1 (8.9) in first X-ray (P = 0.02). First X-ray mean anterior body height% loss was 37.5 (17.6) and 53.2 (16.1) in the non-operative and operative groups, respectively (P = 0.04). Conclusions Upright radiographs are useful in guiding traumatic vertebral fracture management decisions. Larger studies are needed to determine the degree of change in kyphosis between CT and first standing radiograph that is suggestive of operative management. Trial registration number and date of registration Not applicable.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.