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International audience; Acute peripheral vestibulopathy leads to a cascade of symptoms involving balance and gait disorders that are particularly disabling for vestibular patients. Vestibular rehabilitation protocols have proven to be effective in improving vestibular compensation in clinical practice. Yet, the underlying neurobiological correlates remain unknown. The aim of this study was to highlight the behavioural and cellular consequences of a vestibular rehabilitation protocol adapted to a rat model of unilateral vestibular neurectomy. We developed a progressive sensory-motor rehabilitation task, and the behavioural consequences were quantified using a weight-distribution device. This analysis method provides a precise and ecological analysis of posturolocomotor vestibular deficits. At the cellular level, we focused on the analysis of plasticity mechanisms expressed in the vestibular nuclei. The results obtained show that vestibular rehabilitation induces a faster recovery of posturolocomotor deficits during vestibular compensation associated with a decrease in neurogenesis and an increase in microgliogenesis in the deafferented medial vestibular nucleus. This study reveals for the first time a part of the underlying adaptative neuroplasticity mechanisms of vestibular rehabilitation. These original data incite further investigation of the impact of rehabilitation on animal models of vestibulopathy. This new line of research should improve the management of vestibular patients.

International audience; Pollen characters of the Algerian oleaster (Olea europaea subsp. europaea var. sylvestris [Mill.] Lehr) from eight ecotypes were analysed to evaluate the geo-climatic effect of their environment. Samples were collected along an altitudinal gradient from western to central Algeria. Eighteen morphological characters of the pollen grains were studied using scanning electron microscopy (SEM). The results show significant inter-populations variability. The geo-climatic conditions, duration and timing of dry periods vary from one area to another. Depending on the area, the length of the dry period (P p ≤ 2T) coincides more or less with anthesis periods. No significant geo-climatic effects on exine parameters were detected, except for lumina density (LD) and mean lumina diameter (Lm). However, polar axis (P), pollen size index (PSI) and pollen colpis length (PCL) were found to be related to latitude, longitude and temperature. LD and Lm were strongly linked to the pollen parameters, resulting in variation in pollen shape and size. Depending on the geo-climatic conditions, three morphotypes appear. The morphotype from a site with high temperature, low humidity associated with a long dry period is characterised by small pollen size, low lumina surface area and high lumina density/100 μm2 and vice versa. The results indicate that the exine has played an important role in the environmental adaption in these wild populations.

Damage to cochlear primary afferent synapses has been shown to be a key factor in various auditory pathologies. Similarly, the selective lesioning of primary vestibular synapses might be an underlying cause of peripheral vestibulopathies that cause vertigo and dizziness, for which the pathophysiology is currently unknown. To thoroughly address this possibility, we selectively damaged the synaptic contacts between hair cells and primary vestibular neurons in mice through the transtympanic administration of a glutamate receptor agonist. Using a combination of histological and functional approaches, we demonstrated four key findings: (1) selective synaptic deafferentation is sufficient to generate acute vestibular syndrome with characteristics similar to those reported in patients; (2) the reduction of the vestibulo-ocular reflex and posturo-locomotor deficits mainly depends on spared synapses; (3) damaged primary vestibular synapses can be repaired over the days and weeks following deafferentation; and (4) the synaptic repair process occurs through the re-expression and re-pairing of synaptic proteins such as CtBP2 and SHANK-1. Primary synapse repair might contribute to re-establishing the initial sensory network. Deciphering the molecular mechanism that supports synaptic repair could offer a therapeutic opportunity to rescue full vestibular input and restore gait and balance in patients., Summary: The molecular rearrangements of the synaptic proteins that accompany the deafferentation and subsequent reafferentation of the inner ear sensors following an excitotoxic insult are demonstrated for the first time.

The generation of replacement inner ear hair cells (HCs) remains a challenge and stem cell therapy holds the potential for developing therapeutic solutions to hearing and balance disorders. Recent developments have made significant strides in producing mouse otic progenitors using cell culture techniques to initiate HC differentiation. However, no consensus has been reached as to efficiency and therefore current methods remain unsatisfactory. In order to address these issues, we compare the generation of otic and HC progenitors from embryonic stem (ES) cells in two cell culture systems: suspension vs. adherent conditions. In the present study, an ES cell line derived from an Atoh1-green fluorescent protein (GFP) transgenic mouse was used to track the generation of otic progenitors, initial HCs and to compare these two differentiation systems. We used a two-step short-term differentiation method involving an induction period of 5 days during which ES cells were cultured in the presence of Wnt/transforming growth factor TGF-β inhibitors and insulin-like growth factor IGF-1 to suppress mesoderm and reinforce presumptive ectoderm and otic lineages. The generated embryoid bodies were then differentiated in medium containing basic fibroblast growth factor (bFGF) for an additional 5 days using either suspension or adherent culture methods. Upon completion of differentiation, quantitative polymerase chain reaction analysis and immunostaining monitored the expression of otic/HC progenitor lineage markers. The results indicate that cells differentiated in suspension cultures produced cells expressing otic progenitor/HC markers at a higher efficiency compared with the production of these cell types within adherent cultures. Furthermore, we demonstrated that a fraction of these cells can incorporate into ototoxin-injured mouse postnatal cochlea explants and express MYO7A after transplantation. Copyright © 2016 John Wiley & Sons, Ltd.

Breast cancer frequency in human and other mammal female populations has worryingly increased lately. The acute necessity for taxonomy of the aetiological factors along with seeking for new diagnostic tools and therapy procedures aimed at reducing mortality have yielded in an intense research effort worldwide. Surgery is a regular method to counteract extensive development of breast cancer and prevent metastases provided that negative surgical margins are achieved. This highly technical challenge requires fast, extremely sensitive and selective discrimination between malignant and benign tissues even down to molecular level. The particular advantages of Raman spectroscopy, such as high chemical specificity, and the ability to measure raw samples and optical responses in the visible or near-infrared spectral range, have recently recommended it as a means with elevated potential in precise diagnostic in oncology surgery. This review spans mainly the latter 10 years of exceptional efforts of scientists implementing Raman spectroscopy as a nearly real-time diagnostic tool for clean margins assessment in mastectomy and lumpectomy. Although greatly contributing to medical discoveries for the wealth of humanity, animals as patients have benefitted less from advances in surgery diagnostic using Raman spectroscopy. This work also dedicates a few lines to applications of surface enhanced Raman spectroscopy in veterinary oncological surgery.

This paper shows some results of our work on the use of Surface Enhanced Raman Scattering as an ex vivo and in vivo diagnostic means in veterinary surgery and oncology. Also, as part of the involved research, interspecies discrimination of adipose constituents and body fluids is illustrated. These later outcomes would supply efficient instruments to forensics. An innovative system based on surface enhanced Raman scattering, primarily used in small animal surgery, will add to the ongoing research on tumour margin assessment. Samples from animal patients following therapeutic mastectomy have been investigated ex vivo using a LABRAM HR 800 micro-Raman spectrometer. Spectra were collected from 100 cm−1 to 4000 cm−1 using a 632 nm HeNe laser, which to date has been reported on in vitro human samples only. A surface enhanced Raman effect of up to 107 has been obtained on areas of surgery instruments either raw or coated with silver or gold. This dramatically improves spectral resolution and reduces the accumulation time down to 60 s, which would allow for real time diagnostic.

International audience; In the field of keratoconus treatment, a lipid-based liquid crystal nanoparticles system has been developed to improve the preocular retention and ocular bioavailability of riboflavin, a water-soluble drug. The formulation of this ophthalmic drug delivery system was optimized by a simplex lattice experimental design. The delivery system is composed of three main components that are mono acyl glycerol (monoolein), poloxamer 407 and water and two secondary components that are riboflavin and glycerol (added to adjust the osmotic pressure). The amounts of these three main components were selected as the factors to systematically optimize the dependent variables that are the encapsulation efficiency and the particle size. In this way, 12 formulas describing experimental domain of interest were prepared. Results obtained using small angle X-rays scattering (SAXS) and cryo-transmission electron microscopy (cryo-TEM) evidenced the presence of nano-objects with either sponge or hexagonal inverted structure. In the zone of interest, the percentage of each component was determined to obtain both high encapsulation efficiency and small size of particles. Two optimized formulations were found: F7 and F1. They are very close in the ternary phase diagram as they contain 6.83% of poloxamer 407; 44.18% and 42.03% of monoolein; 46.29% and 48.44% of water for F7 and F11, respectively. These formulations displayed a good compromise between inputs and outputs investigated.