Phoenixin influences the excitability of nucleus of the solitary tract neurones,effects which are modified by environmental and glucocorticoid stress

Phoenixin (PNX) is a neuropeptide shown to play roles in the control of reproduction. The nucleus of the solitary tract (NTS), a critical autonomic integrating centre in the hindbrain, is one of many areas with dense expression of PNX. Using coronal NTS slices obtained from male Sprague‐Dawley rats, the present study characterised the effects of PNX on both spike frequency and membrane potential of NTS neurones. Extracellular recordings demonstrated that bath‐applied 10 nmol L^‐1 PNX increased the firing frequency in 32% of NTS neurones, effects which were confirmed with patch‐clamp recordings showing that 50% of NTS neurones tested depolarised in response to application of the peptide. Surprisingly, the responsiveness to PNX in NTS neurones then declined suddenly to 9% (P < 0.001). This effect was subsequently attributed to stress associated with construction in our animal care facility because PNX responsiveness was again observed in slices from rats delivered and maintained in a construction‐free facility. We then examined whether this loss of PNX responsiveness could be replicated in rats placed on a chronic stress regimen involving ongoing corticosterone (CORT) treatment in the construction‐free facility. Slices from animals treated in this way showed a similar lack of neuronal responsiveness to PNX (9.1 ± 3.9%) within 2 weeks of CORT treatment. These effects were specific to PNX responsiveness because CORT treatment had no effect on the responsiveness of NTS neurones to angiotensin II. These results are the first to implicate PNX with respect to directly controlling the excitability of NTS neurones and also provide intriguing data showing the plasticity of these effects associated with environmental and glucocorticoid stress levels of the animal.     

Sonoanatomy and Pathology of the Gluteus Minimus Tendon

Gluteus minimus disorders are a potential source of greater trochanteric or anterior hip pain. Disorders of the gluteus minimus tendon most commonly occur in conjunction with gluteus medius tendon abnormalities but can also occur in isolation. Understanding the sonoanatomy of the gluteus minimus muscle-tendon unit is a prerequisite for recognizing and characterizing gluteus minimus tendon disorders, which, in turn, guides treatment for patients with greater trochanteric or anterior hip pain syndromes.     

Recent Administration of Iodinated Contrast Renders Core Infarct Estimation Inaccurate Using RAPID Software

BACKGROUND AND PURPOSE:Automated CTP software is increasingly used for extended window emergent large-vessel occlusion to quantify core infarct. We aimed to assess whether RAPID software underestimates core infarct in patients with an extended window recently receiving IV iodinated contrast.MATERIALS AND METHODS:We reviewed a prospective, single-center data base of 271 consecutive patients who underwent CTA ± CTP for acute ischemic stroke from May 2018 through January 2019. Patients with emergent large-vessel occlusion confirmed by CTA in the extended window (>6 hours since last known well) and CTP with RAPID postprocessing were included. Two blinded raters independently assessed CT ASPECTS on NCCT performed at the time of CTP. RAPID software used relative cerebral blood flow of <30% as a surrogate for irreversible core infarct. Patients were dichotomized on the basis of receiving recent IV iodinated contrast (<8 hours before CTP) for a separate imaging study.RESULTS:The recent IV contrast and contrast-naïve cohorts comprised 23 and 15 patients, respectively. Multivariate linear regression analysis demonstrated that recent IV contrast administration was independently associated with a decrease in the RAPID core infarct estimate (proportional increase = 0.34; 95% CI, 0.12–0.96; P = .04).CONCLUSIONS:Patients who received IV iodinated contrast in proximity (<8 hours) to CTA/CTP as part of a separate imaging study had a much higher likelihood of core infarct underestimation with RAPID compared with contrast-naïve patients. Over-reliance on RAPID postprocessing for treatment disposition of patients with extended window emergent large-vessel occlusion should be avoided, particularly with recent IV contrast administration.

Quantifying core infarction versus viable ischemic penumbra is at the crux of patient selection for mechanical thrombectomy (MT) in the setting of anterior circulation emergent large-vessel occlusion (ELVO). While patients with large infarcts tend to demonstrate worse clinical outcomes following reperfusion, successful recanalization of sizable ischemic penumbra, indicative of salvageable tissue, may result in drastic clinical improvement.¹ Segregation of core infarction from ischemic penumbra is particularly relevant for extended window ELVOs (>6 hours since last known well [LKW]).^2,3The semiquantitative ASPECTS system is highly predictive of clinical outcome with ELVO but demonstrates high inter- and intrareader variability.^4,5 Additionally, ASPECTS regions are volumetrically weighted unequally; consequently, patients with the same ASPECTS may have different core infarct volumes depending on the regions involved. The automated quantitative RApid processing of PerfusIon and Diffusion (RAPID; iSchemaView) CTP platform offers standardized and numeric estimation of core infarct and ischemic penumbra, lessening reliance on neuroradiologic ASPECTS interpretation. RAPID estimates a variety of perfusion parameters indicative of cerebral hemodynamics at the moment of scanning. Accordingly, RAPID may predict tissue fate in the hyperacute setting (<1 hour since LKW). NCCT, however, is dependent on parenchymal hypoattenuation, which becomes apparent at least several hours from symptom onset.RAPID software has been validated in multiple clinical trials, notably in DAWN (DWI or CTP Assessment with Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention with Trevo) and DEFUSE-3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3), both using RAPID for patient selection for MT in extended window ELVOs. Patients allocated to MT versus best medical therapy alone in the DAWN and DEFUSE-3 trials demonstrated markedly better clinical outcomes with unprecedented numbers needed to treat (NNT) of 2.8 and 4, respectively, to achieve functional independence at 90 days.^2,3Through more ubiquitous RAPID use, we encountered a recurrent phenomenon in which transfer patients with extended window ELVO demonstrated MCA territory hypoattenuation on NCCT but with disproportionately small and, in some instances, zero RAPID estimated core infarct. Essentially, all ELVO transfers to our institution are recent recipients of IV iodinated contrast. Given this imaging incongruity and our ongoing need to optimize patient selection for MT, we aimed to assess whether RAPID software underestimated core infarct volume in patients who received recent (<8 hours) IV contrast for a separate imaging study, most commonly CTA ± CTP at an outside hospital before transfer.     

Working memory training and brain structure and function in extremely preterm or extremely low birth weight children

This study in children born extremely preterm (EP; <28 weeks’ gestational age) or extremely low birth weight (ELBW; <1,000 g) investigated whether adaptive working memory training using Cogmed® is associated with structural and/or functional brain changes compared with a placebo program. Ninety‐one EP/ELBW children were recruited at a mean (standard deviation) age of 7.8 (0.4) years. Children were randomly allocated to Cogmed or placebo (45‐min sessions, 5 days a week over 5–7 weeks). A subset had usable magnetic resonance imaging (MRI) data pretraining and 2 weeks posttraining (structural, n = 48; diffusion, n = 43; task‐based functional, n = 18). Statistical analyses examined whether cortical morphometry, white matter microstructure and blood oxygenation level‐dependent (BOLD) signal during an n‐back working memory task changed from pretraining to posttraining in the Cogmed and placebo groups separately. Interaction analyses between time point and group were then performed. There was a significant increase in neurite density in several white matter regions from pretraining to posttraining in both the Cogmed and placebo groups. BOLD signal in the posterior cingulate and precuneus cortices during the n‐back task increased from pretraining to posttraining in the Cogmed but not placebo group. Evidence for group‐by‐time interactions for the MRI measures was weak, suggesting that brain changes generally did not differ between Cogmed and placebo groups. Overall, while some structural and functional MRI changes between the pretraining and posttraining period in EP/ELBW children were observed, there was little evidence of training‐induced neuroplasticity, with changes generally identified in both groups. Trial registration Australian New Zealand Clinical Trials Registry, anzctr.org.au ; ACTRN12612000124831.     

Increased activation of the fear neurocircuitry in children exposed to violence

Most studies investigating the effect of childhood trauma on the brain are retrospective and mainly focus on maltreatment, whereas different types of trauma exposure such as growing up in a violent neighborhood, as well as developmental stage, could have differential effects on brain structure and function. The current magnetic resonance imaging study assessed the effect of trauma exposure broadly and violence exposure more specifically, as well as developmental stage on the fear neurocircuitry in 8‐ to 14‐year‐old children and adolescents (N = 69). We observed reduced hippocampal and increased amygdala volume with increasing levels of trauma exposure. Second, higher levels of violence exposure were associated with increased activation in the amygdala, hippocampus, and ventromedial prefrontal cortex during emotional response inhibition. This association was specifically observed in children younger than 10 years. Finally, increased functional connectivity between the amygdala and brainstem was associated with higher levels of violence exposure. Based on the current findings, it could be hypothesized that trauma exposure during childhood results in structural changes that are associated with later risk for psychiatric disorders. At the same time, it could be postulated that growing up in an unsafe environment leads the brain to functionally adapt to this situation in a way that promotes survival, where the long‐term costs or consequences of these adaptations are largely unknown and an area for future investigations.