Paradoxical anti-epileptic effects of a GluR5 agonist of kainate receptors.

International audienceKainate generates in adult hippocampal neurons a seizure but also a massive excitation of interneurons and a dramatic increase of the inhibitory drive that impinges on principal cells. This "overinhibition" is largely mediated by GluR5-containing kainate receptors that are enriched on interneurons. Here, using the neonatal intact hippocampus in vitro and the triple chamber, we first show that this mechanism is fully operative in neonatal neurons. We then report that application to one hippocampus of (RS)-2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid-a relatively selective agonist of GluR5 containing kainate receptors-depresses the propagation of seizure generated in the opposite hippocampus by a convulsive agent. We conclude that the selective excitation of interneurons by GluR5-containing kainate receptor agonists opens a new therapeutic approach for the epilepsies

Basic Concepts in Understanding Recovery of Function in Vestibular Reflex Networks during Vestibular Compensation

Unilateral peripheral vestibular lesions produce a syndrome of oculomotor and postural deficits with the symptoms at rest, the static symptoms, partially or completely normalizing shortly after the lesion due to a process known as vestibular compensation. The symptoms are thought to result from changes in the activity of vestibular sensorimotor reflexes. Since the vestibular nuclei must be intact for recovery to occur, many investigations have focused on studying these neurons after lesions. At present, the neuronal plasticity underlying early recovery from the static symptoms is not fully understood. Here we propose that knowledge of the reflex identity and input–output connections of the recorded neurons is essential to link the responses to animal behavior. We further propose that the cellular mechanisms underlying vestibular compensation can be sorted out by characterizing the synaptic responses and time course for change in morphologically defined subsets of vestibular reflex projection neurons. Accordingly, this review focuses on the perspective gained by performing electrophysiological and immunolabeling studies on a specific subset of morphologically defined, glutamatergic vestibular reflex projection neurons, the principal cells of the chick tangential nucleus. Reference is made to pertinent findings from other studies on vestibular nuclei neurons, but no comprehensive review of the literature is intended since broad reviews already exist. From recording excitatory and inhibitory spontaneous synaptic activity in principal cells, we find that the rebalancing of excitatory synaptic drive bilaterally is essential for vestibular compensation to proceed. This work is important for it defines for the first time the excitatory and inhibitory nature of the changing synaptic inputs and the time course for changes in a morphologically defined subset of vestibular reflex projection neurons during early stages of vestibular compensation

Admission profile and discharge outcomes for infants aged less than 6 months admitted to inpatient therapeutic care in 10 countries. A secondary data analysis.

Evidence on the management of acute malnutrition in infants aged less than 6 months (infants <6mo) is scarce. To understand outcomes using current protocols, we analysed a sample of 24 045 children aged 0-60 months from 21 datasets of inpatient therapeutic care programmes in 10 countries. We compared the proportion of admissions, the anthropometric profile at admission and the discharge outcomes between infants <6mo and children aged 6-60 months (older children). Infants <6mo accounted for 12% of admissions. The quality of anthropometric data at admission was more problematic in infants <6mo than in older children with a greater proportion of missing data (a 6.9 percentage point difference for length values, 95% CI: 6.0; 7.9, P < 0.01), anthropometric measures that could not be converted to indices (a 15.6 percentage point difference for weight-for-length z-score values, 95% CI: 14.3; 16.9, P < 0.01) and anthropometric indices that were flagged as outliers (a 2.7 percentage point difference for any anthropometric index being flagged as an outlier, 95% CI: 1.7; 3.8, P < 0.01). A high proportion of both infants <6mo and older children were discharged as recovered. Infants <6mo showed a greater risk of death during treatment (risk ratio 1.30, 95% CI: 1.09; 1.56, P < 0.01). Infants <6mo represent an important proportion of admissions to therapeutic feeding programmes, and there are crucial challenges associated with their care. Systematic compilation and analysis of routine data for infants <6mo is necessary for monitoring programme performance and should be promoted as a tool to monitor the impact of new guidelines on care

Immune Modulating Peptides for the Treatment and Suppression of Multiple Sclerosis

Multiple sclerosis (MS) is a neurodegenerative disease in which the immune system recognizes proteins of the myelin sheath as antigenic, thus initiating an inflammatory reaction in the central nervous system. This leads to demyelination of the axons, breakdown of the blood-brain barrier, and lesion formation. Current therapies for the treatment of MS are generally non-specific and weaken the global immune system, thus making the individual susceptible to opportunistic infections. Antigenic peptides and their derivatives are becoming more prevalent for investigation as therapeutic agents for MS because they possess immune-specific characteristics. In addition, other peptides that target vital components of the inflammatory immune response have also been developed. Therefore, the objectives of this review are to (a) summarize the immunological basis for the development of MS, (b) discuss specific and non-specific peptides tested in EAE and in humans, and (c) briefly address some problems and potential solutions with these novel therapies

Association of Type 1 Diabetes vs Type 2 Diabetes Diagnosed During Childhood and Adolescence With Complications During Teenage Years and Young Adulthood

The burden and determinants of complications and comorbidities in contemporary youth-onset diabetes are unknown

The effect of asthma on transitions to college: An exploratory study

This study explored the experiences of University of Northern Iowa students with asthma and the need for additional support for students with asthma, particularly regarding policy and cultural change. This study is significant because 9.1% of college students reported having asthmatic conditions in 2016 (Mullins et al., 2017). Many researchers have found that students with asthma are more likely to miss school and work, have increased rates of distress and anxiety, and decreased quality of life. Therefore, asthma can affect all aspects of an individual’s life. Transitioning from high school to college can be a stressful change even under the best of circumstances. For those with asthma, these stressors may also include anxiousness about medications and overall disease management along with the typical factors including making friends, stress, differing sleep schedules, and loneliness. The benefit of this study will be to gather information from UNI students regarding their opinion on the need for a policy or program to help students with asthma make the transition from high school as smooth as possible taking into account these extra factors. This is significant for school officials in order to create policies to benefit students with asthma and make the transition from high school to college as smooth as possible

Interneurones are not so dormant in temporal lobe epilepsy: a critical reappraisal of the dormant basket cell hypothesis.

International audienceOne axiom at the basis of epilepsy research is that there exists an imbalance between excitation and inhibition. This abnormality can be achieved by an increase of excitation on principal cells, a decreased inhibition (i.e. disinhibition) or both. This review focuses on dysfunction of inhibition, and in particular on the 'dormant basket cell hypothesis'. This hypothesis states that, (1) interneurones are functionally disconnected from excitatory afferents, resulting in hyperexcitability of principal neurones and loss of paired pulse inhibition, (2) when properly activated, interneurones can still perform their task, i.e. suppress epileptiform activity and restore paired pulse inhibition. The aim of this review is to discuss the evidence in support of the 'dormant basket cell hypothesis'. We will first discuss the rationale underlying the hypothesis and the criteria needed to validate the hypothesis. We will then show that, (1) the key experimental data offered in support of the hypothesis (Bekenstein and Lothman, 1993. Dormancy of inhibitory interneurones in a model of temporal lobe epilepsy. Science 259, 97-100; Sloviter, 1991. Permanently altered hippocampal structure, excitability, and inhibition after experimental status epilepticus in the rat: the 'dormant basket cell' hypothesis and its relevance to temporal lobe epilepsy. Hippocampus 1, 41-66) are difficult to interpret, and (2) recent recordings from interneurones in epileptic tissue argue against the hypothesis. The 'dormant basket cell hypothesis' is then discussed in the broader context of disinhibition