Mechanisms of action of intracerebral neural implants: studies on nigral and striatal grafts to the lesioned striatum

The ability of intracerebrally implanted grafts of neural tissues to promote functional recovery in brain-damaged recipient animals has raised the question of how such implants exert their functional effects. Non-specific, diffuse release of active compounds may be sufficient to restore defective neurotransmission in a denervated brain region, for example, or to provide trophic support for the survival and regeneration of damaged host neurons. The positive therapeutic effects of adrenal medullary grafts, recently reported in patients with Parkinson's disease, are likely to reflect such nonspecific hormonal or neurohumoral mechanisms. Morphological and electrophysiological studies, on the other hand, have shown that grafted fetal neurons can establish extensive efferent synaptic connections with previously denervated or neuron-depleted host brain regions and become at least partially integrated into the host neuronal circuitry. In the damaged nigrostriatal system, grafts of fetal nigral or striatal neurons can restore normal synaptic transmitter release and can also participate in a partial reconstruction of functional neural circuits in the host brain. This indicates that the potential of intracerebral grafts to induce or improve behavioral recovery in brain-damaged recipients rests on the multitude of trophic, neurohumoral and synaptic mechanisms that may allow the implanted tissue to promote host brain function and repair.     

Insulin receptors and insulin action in dissociated brain cells

The present study was conducted to characterize insulin receptors and insulin action in rat brain cells. Binding of [125I]insulin to cells obtained by mechanically dissociating rat brains was 86% specific, time-dependent and reached equilibrium within 90 min. The t1/2 of association was 14 min and t1/2 of dissociation was 8 min. Scatchard analysis demonstrated the typical curvilinear plot providing high affinity (0.03 nM) and low affinity (6.6 nM) binding sites. The total number of binding sites were 0.15 pmol/mg protein. Crosslinking of [125I]insulin to its receptors on dissociated brain cells followed by SDS-PAGE and autoradiography showed that the alpha-subunit of the receptor had a molecular weight of 122,000. This was in contrast with a molecular weight of 134,000 for the liver alpha-subunit. Incubation of dissociated brain cells with insulin resulted in a concentration-dependent inhibition of total [3H]norepinephrine (NE) uptake. This inhibitory effect of insulin on [3H]NE uptake was sodium ion-dependent suggesting that 80-90% of the sodium ion-dependent uptake was insulin-sensitive. Incubation of lectin-purified insulin receptors with insulin resulted in a time- and concentration-dependent stimulation of phosphorylation of the tyrosine residue of an exogenous substrate poly (Glu, Tyr) (4:1). In addition, insulin also stimulated the autophosphorylation of the beta-subunit of the insulin receptors. These observations corroborate our contention that insulin exerts neuromodulatory effects mediated by the specific insulin receptors in the brain.     

Infant brain imaging using magnetoencephalography: Challenges,solutions, and best practices

The excellent temporal resolution and advanced spatial resolution of magnetoencephalography (MEG) makes it an excellent tool to study the neural dynamics underlying cognitive processes in the developing brain. Nonetheless, a number of challenges exist when using MEG to image infant populations. There is a persistent belief that collecting MEG data with infants presents a number of limitations and challenges that are difficult to overcome. Due to this notion, many researchers either avoid conducting infant MEG research or believe that, in order to collect high‐quality data, they must impose limiting restrictions on the infant or the experimental paradigm. In this article, we discuss the various challenges unique to imaging awake infants and young children with MEG, and share general best‐practice guidelines and recommendations for data collection, acquisition, preprocessing, and analysis. The current article is focused on methodology that allows investigators to test the sensory, perceptual, and cognitive capacities of awake and moving infants. We believe that such methodology opens the pathway for using MEG to provide mechanistic explanations for the complex behavior observed in awake, sentient, and dynamically interacting infants, thus addressing core topics in developmental cognitive neuroscience.     

Morphologische Untersuchungen zur Form der Cupula in der Bogengangsampulle

Hintergrund und Fragestellung. In der Ampulle des Bogengangs ist die Cupula, ?hnlich wie die Tektorialmembran in der Kochlea, das wesentliche Bindeglied in der Reizübertragung von Flüssigkeitsbewegungen auf die Haarzellen. über die physiologische Cupulabewegung gibt es erst seit Ende der 1970er Jahre klare Vorstellungen. Man geht von einer stabilen Anhaftung der Cupula an der Ampullenwand aus, w?hrend Bewegungen v. a. in der Cupulamitte und an der Basis stattfinden.     

Day 1 serum lactate values in preterm infants less than 32 weeks gestation

Base deficit and serum lactate concentrations may be important prognostic indicators in preterm infants. We sought to (1) determine the relationship between day 1 serum lactate values and base deficit and (2) determine the relationship between day 1 biochemical parameters and adverse outcome in preterm infants <32 weeks. This was a retrospective study of all patients less than 32 weeks gestation admitted to neonatal intensive care unit over a 6-month period. All blood gases performed during the first 24 h post delivery were analysed. Adverse outcome was defined as death, severe (grade 3 or 4) intraventricular haemorrhage or periventricular leukomalaica on cranial ultrasonography. Patients were excluded if there was a known lethal malformation or cardiac defect. Seventy-two infants had a total of 473 lactate levels performed in the first 24 h. Mean (SD) gestational age was 29 (2.3) weeks, mean (SD) birth weight 1.28 (0.42) kg. Mean (SD) lactate values in first 6 h was 4.63 (3.69), at 12 h 3.08 (2.6), at 18 h 2.47 (2.68) and 2.08 (2.74) mmol/l at 24 h. There was a strong correlation between lactate values and base deficit values (R value 0.8, p < 0.01). Mean base deficit values at 6 h were 5.9 (4.5), at 12 h 3.8 (3.9), at 18 h 3.6 (3.1) and at 24 h 4.1 (3.8) mmol/l. A single lactate value greater than 5.6 mmol/l had a sensitivity of 100% and specificity of 85% of identifying adverse outcome. Persistently elevated or worsening lactates were associated with adverse outcome. There is a strong correlation between lactate values and base deficit on day 1 of life. Serial lactate measurements greater than 5.6 mmol/l predict adverse outcome and may aid the clinician in bedside decision making.     

IL-1β is released from the host brain following transplantation but does not compromise embryonic dopaminergic neuron survival

Poor survival of transplanted dopaminergic (DA) neurons remains a serious obstacle to the success of cell replacement therapy as an alternative to the current treatments for Parkinson's disease. We have examined the temporal release profile of an inflammatory cytokine, interleukin-1 beta (IL-1 beta) following transplantation of fetal mesencephalic tissue into the rat striatum. The amounts of IL-1 beta released in vivo when added to cultures of embryonic DA neurons, did not significantly reduce the survival of DA neurons in vitro, and inclusion of the naturally-occurring IL-1 receptor antagonist, IL-1ra, did not appear to affect the numbers of surviving DA neurons present after 5 days in vitro. Neither did inclusion of IL-1ra in cell suspensions during transplantation increase the survival of transplanted fetal DA neurons. Thus, although IL-1 beta is released following implantation of a neural transplant, we suggest that this pro-inflammatory cytokine does not play an active role in reducing survival of transplanted DA neurons, unlike other cytokines such as tumor necrosis factor alpha. Modulation of IL-1 beta activity, therefore, will not offer significant improvements to neural transplantation as a treatment for PD.     

Right ventricular dynamic cardiomyoplasty: an experimental model

The effectiveness of dynamic cardiomyoplasty as a means of haemodynamic support in heart failure remains controversial. We have undertaken a study of right ventricular dynamic cardiomyoplasty in sheep using intravenous propranolol to provoke heart failure. Muscle conditioning was performed with cardiomyostimulators following a previously established protocol. We performed multiple invasive measurements of haemodynamic parameters including arterial blood pressure, cardiac output, pulmonary artery capillary wedge pressure, right ventricular dp/dt and end diastolic pressures. These were performed before induction of heart failure, after induction of heart failure, and with pacing of the cardiomyoplasty flap in established heart failure. Our results confirm that we were able to establish significant heart failure and that subsequent pacing of the conditioned muscle flap was able to return cardiac output and right ventricular function to their pre-failure control levels.     

Comparative study of endoscopic clips: duration of attachment at the site of clip application

BACKGROUND: Several designs of endoscopic clips are now commercially available, and the indications for endoclip application are rapidly expanding. However, very limited data have been published to aid in choosing between the different types of endoclips. OBJECTIVE: To compare the duration of clip attachment between all commercially available endoclips. SETTING: Long-term experiments on 50-kg pigs under general anesthesia. DESIGN AND INTERVENTIONS: Upper endoscope was inserted into the stomach. One clip of each type (Resolution clip, TriClip, and HX-5L clip) was placed along the same gastric fold at a distance of 0.5 to 1 cm from each other. The animals were recovered. In pig nos. 1 and 2, repeat endoscopy was performed after 2 and 4 weeks. In pig nos. 3 to 5, endoscopy was repeated after 1, 2, and 5 weeks. MAIN OUTCOME MEASUREMENTS: Duration of clip retention at the site of application. RESULTS: In all animals, only the Resolution endoclip remained attached to the site of application for the entire duration of the study (4-5 weeks). No TriClips or HX-5L clips were attached at the 4- to 5-week follow-up endoscopies. Most of the TriClips (67%) detached within the first week after application. Most of the HX-5L clips (80%) dislodged within the first 2 weeks of follow-up. LIMITATIONS: The study was performed in a porcine model with a small number of animals. CONCLUSIONS: The Resolution clip has the longest duration of retention at the site of application (more than 4-5 weeks) and should be preferred when long-term attachment of endoclips is necessary.