Concept and Development of an Electronic Framework Intended for Electrode and Surrounding Environment Characterization In Vivo.

There has been substantial progress over the last decade towards miniaturizing implantable microelectrodes for use in Active Implantable Medical Devices (AIMD). Compared to the rapid development and complexity of electrode miniaturization, methods to monitor and assess functional integrity and electrical functionality of these electrodes, particularly during long term stimulation, have not progressed to the same extent. Evaluation methods that form the gold standard, such as stimulus pulse testing, cyclic voltammetry and electrochemical impedance spectroscopy, are either still bound to laboratory infrastructure (impractical for long term in vivo experiments) or deliver no comprehensive insight into the material's behaviour. As there is a lack of cost effective and practical predictive measures to understand long term electrode behaviour in vivo, material investigations need to be performed after explantation of the electrodes. We propose the analysis of the electrode and its environment in situ, to better understand and correlate the effects leading to electrode failure. The derived knowledge shall eventually lead to improved electrode designs, increased electrode functionality and safety in clinical applications. In this paper, the concept, design and prototyping of a sensor framework used to analyse the electrode's behaviour and to monitor diverse electrode failure mechanisms, even during stimulation pulses, is presented. We focused on the electronic circuitry and data acquisition techniques required for a conceptual multi-sensor system. Functionality of single modules and a prototype framework have been demonstrated, but further work is needed to convert the prototype system into an implantable device. In vitro studies will be conducted first to verify sensor performance and reliability.

Neonatal arrhythmias in Turner syndrome: a case report and review of the literature.

BACKGROUND: While left-sided congenital heart defects have been well described in females with Turner syndrome (45, X), the literature is scarce regarding arrhythmias in this patient population. CASE SUMMARY: A full-term neonate referred to cardiology was found to have a non-apex forming left ventricle and partial anomalous pulmonary venous return. During the echocardiogram, she developed atrial flutter, followed by orthodromic reentrant supraventricular tachycardia (SVT). She was started on propranolol and eventually switched to sotalol due to breakthrough SVT. A genetics evaluation revealed Turner syndrome with complete monosomy X (45, X). The patient is now 18 months old and has not had any further arrhythmias. DISCUSSION: We present a rare case of atrial flutter followed by supraventricular tachycardia in a neonate with Turner syndrome and left-sided heart defects. This case highlights the importance of early and precise investigation of cardiac abnormalities in neonatal patients, especially among females with Turner syndrome given their relatively higher risk of cardiovascular disease compared to the general population.

Impact of indolent inflammation on neonatal hypoxic-ischemic brain injury in mice.

This report describes a new experimental model to evaluate the effect of a recurrent systemic inflammatory challenge, after cerebral hypoxia-ischemia in immature mice, on the progression of brain injury. Treatment with a low dose of lipopolysaccharide (E. coli O55:B5, 0.2mg/kg for 3 days, then 0.1mg/kg for 2 days) daily for 5 days after unilateral cerebral hypoxia-ischemia (right carotid ligation followed by 35min in 10% O2) in 10-day-old mice resulted in increased right forebrain tissue damage (35.6% reduction in right hemisphere volume compared to 20.6% reduction in saline-injected controls), in bilateral reductions in corpus callosum area (by 12%) and myelin basic protein immunostaining (by 19%), and in suppression of injury-related right subventricular zone cellular proliferation. The post-hypoxic-ischemic lipopolysaccharide regimen that amplified brain injury was not associated with increased mortality, nor with changes in body temperature, weight gain or blood glucose concentrations. The results of the present study demonstrate that systemic inflammation influences the evolution of tissue injury after neonatal cerebral hypoxia-ischemia and may also impair potential recovery mechanisms.

Distribution of progesterone receptor immunoreactivity in the fetal and neonatal rat forebrain.

Steroid hormones play an influential role in neural development. In addition to androgens and estrogens of fetal and neonatal origin, the developing brain may also be exposed to progesterone. In this regard, identifying forebrain nuclei that are sensitive to progesterone during neural development may elucidate the impact of progesterone on the developing brain. Using immunocytochemistry, the present study documented the distribution of progesterone receptor (PR) expression in the rat forebrain from embryonic day (E) 17 through postnatal day (P) 28. The results indicate that PR expression in the developing brain is extensive, present in numerous forebrain nuclei, but transient, in that PR expression was absent in most nuclei by P28. Regions displaying the highest levels of PR-immunoreactivity (PRir) were found in preoptic and hypothalamic nuclei including the medial preoptic, anteroventral periventricular, arcuate, and ventromedial nuclei. PRir was moderately abundant in the limbic region, particularly in subdivisions of the amygdala, the bed nucleus of the stria terminalis, and hippocampus. The choroid plexus and neocortex were additional structures that demonstrated relatively abundant levels of PRir. The presence PR expression in the developing forebrain implicates the involvement of progesterone and PR in fundamental mechanisms of neural development.

Neonatal mice possessing an Sry transgene show a masculinized pattern of progesterone receptor expression in the brain independent of sex chromosome status.

To assess the relative roles of sex chromosome genes and gonadal steroid hormones in producing sex differences in progesterone receptor (PR) expression in the forebrain of neonatal mice, we used mice in which the Sry gene had been deleted from the Y-chromosome and inserted as a transgene on an autosome in both XX and XY genotypes. Levels of PR immunoreactivity (PRir) in the anteroventral periventricular nucleus, the medial preoptic nucleus, and the ventromedial nucleus were significantly higher in mice that possessed an Sry transgene compared with mice that lacked an Sry transgene, regardless of their complement of sex chromosomes (XX vs. XY). This result suggests that sexual differentiation of PR expression in these regions is likely controlled mainly by gonadal hormones, not by the genetic sex of the brain cells. No differences in PRir were detected between wild-type XY mice with the Sry gene on the Y-chromosome and XY mice with the Sry transgene, suggesting that testicular hormones produced in these two genotypes have comparable effects on neural tissue.

Sex differences in progesterone receptor expression: a potential mechanism for estradiol-mediated sexual differentiation.

The differential exposure of males and females to testosterone (T) and its metabolite estradiol (E) contributes to the development of sex differences in the brain. However, the mechanisms by which T and E permanently alter neural development remain virtually unknown. Two regions of the rat preoptic area, the anteroventral periventricular nucleus (AVPv) and the medial preoptic nucleus (MPN), are sexually dimorphic and serve as models for studying the hormonal mechanisms of sexual differentiation. Around birth, these regions express dramatically higher levels of progesterone receptor immunoreactivity (PRir) in males than they do in females. The present study examined the possibility that sexually dimorphic induction of PR expression in these two regions constitutes a potential mechanism of E-mediated sexual differentiation. Prenatal exposure to either T propionate or the synthetic estrogen, diethylstilbestrol, but not dihydrotestosterone propionate, significantly increased PRir levels in the MPN and AVPv of fetal females compared with controls. Prenatal exposure to the aromatase inhibitor, 1,4,6-androstatriene-3,17-dione, significantly reduced PRir in the MPN and AVPv of fetal males, whereas the androgen receptor antagonist flutamide had no effect. This suggests that aromatization of T into E is crucial for the sex difference in PR expression in the MPN and AVPv during development.