Maria Morell

Cortistatin reduces atherosclerosis in hyperlipidemic ApoE-deficient mice and the formation of foam cells

Atherosclerosis is a chronic inflammatory cardiovascular disease that is responsible of high mortality worldwide. Evidence indicates that maladaptive autoimmune responses in the arterial wall play critical roles in the process of atherosclerosis. Cortistatin is a neuropeptide expressed in the vascular system and atherosclerotic plaques that regulates vascular calcification and neointimal formation, and inhibits inflammation in different experimental models of autoimmune diseases. Its role in inflammatory cardiovascular disorders is largely unexplored. The aim of this study is to investigate the potential therapeutic effects of cortistatin in two well-established preclinical models of atherosclerosis, and the molecular and cellular mechanisms involved. Systemic treatment with cortistatin reduced the number and size of atherosclerotic plaques in carotid artery, heart, aortic arch and aorta in acute and chronic atherosclerosis induced in apolipoprotein E-deficient mice fed a high-lipid diet. This effect was exerted at multiple levels. Cortistatin reduced Th1/Th17-driven inflammatory responses and increased regulatory T cells in atherosclerotic arteries and lymphoid organs. Moreover, cortistatin reduced the capacity of endothelial cells to bind and recruit immune cells to the plaque and impaired the formation of foam cells by enhancing cholesterol efflux from macrophages. Cortistatin emerges as a new candidate for the treatment of the clinical manifestations of atherosclerosis.

Ultrastructure of the Odontocete organ of Corti: scanning and transmission electron microscopy.

The morphological study of the Odontocete organ of Corti, together with possible alterations associated with damage from sound exposure, represents a key conservation approach to assess the effects of acoustic pollution on marine ecosystems. By collaborating with stranding networks from several European countries, 150 ears from 13 species of Odontocetes were collected and analyzed by scanning (SEM) and transmission (TEM) electron microscopy. Based on our analyses, we first describe and compare Odontocete cochlear structures and then propose a diagnostic method to identify inner ear alterations in stranded individuals. The two species analyzed by TEM (Phocoena phocoena and Stenella coeruleoalba) showed morphological characteristics in the lower basal turn of high‐frequency hearing species. Among other striking features, outer hair cell bodies were extremely small and were strongly attached to Deiters cells. Such morphological characteristics, shared with horseshoe bats, suggest that there has been convergent evolution of sound reception mechanisms among echolocating species. Despite possible autolytic artifacts due to technical and experimental constraints, the SEM analysis allowed us to detect the presence of scarring processes resulting from the disappearance of outer hair cells from the epithelium. In addition, in contrast to the rapid decomposition process of the sensory epithelium after death (especially of the inner hair cells), the tectorial membrane appeared to be more resistant to postmortem autolysis effects. Analysis of the stereocilia imprint pattern at the undersurface of the tectorial membrane may provide a way to detect possible ultrastructural alterations of the hair cell stereocilia by mirroring them on the tectorial membrane. J. Comp. Neurol. 523:431–448, 2015.

Identifying Cetacean Hearing Impairment at Stranding Sites

While noise is now considered a marine hazard that can directly affect cetaceans and induce a stranding, no clinical approach has yet introduced the detection of a possible hearing loss at a stranding site as a necessary practice. This can be explained by the lack of time when facing vital decisions for the animal’s welfare as well as the unavailability of reliable, lightweight, autonomous, and portable audiometry equipment. Herein, we correlate measured electrophysiological evidence of a permanent threshold shift (PTS) in a rehabilitated striped dolphin (Stenella coeruleoalba) that prevented its release, with the postmortem analysis of an abnormal dilatation of the central nervous system ventricles that prevented the correct acoustic reception of the animal. We further propose to follow a five-minute auditory evoked potential (AEP) standard protocol of hearing measurements in-air on cetaceans at a stranding site that includes the stimulation of auditory brainstem responses (ABRs) with a single 4-μs broadband (> 150 kHz) pulse at three decreasing levels (129, 117, and 105 dBpp re 1 μPa at 15 cm), which covers most of the cetaceans’ known maximum acoustic sensitivity and allows the immediate sensing of an individual’s hearing capability before any final clinical decision is taken.

VIP in neurological diseases: more than a neuropeptide.

A hallmark in most neurological disorders is a massive neuronal cell death, in which uncontrolled immune response is usually involved, leading to neurodegeneration. The vasoactive intestinal peptide (VIP) is a pleiotropic peptide that combines neuroprotective and immunomodulatory actions. Alterations on VIP/VIP receptors in patients with neurodenegerative diseases, together with its involvement in the development of embryonic nervous tissue, and findings found in VIP-deficient mutant mice, have showed the relevance of this endogenous peptide in normal physiology and in pathologic states of the central nervous system (CNS). In this review, we will summarize the role of VIP in normal CNS and in neurological disorders. The studies carried out with this peptide have demonstrated its therapeutic effect and render it as an attractive candidate to be considered in several neurological disorders linked to neuroinflammation or abnormal neural development.

Implementation of a method to visualize noise-induced hearing loss in mass stranded cetaceans

Assessment of the impact of noise over-exposure in stranded cetaceans is challenging, as the lesions that lead to hearing loss occur at the cellular level and inner ear cells are very sensitive to autolysis. Distinguishing ante-mortem pathology from post-mortem change has been a major constraint in diagnosing potential impact. Here, we outline a methodology applicable to the detection of noise-induced hearing loss in stranded cetaceans. Inner ears from two mass strandings of long-finned pilot whales in Scotland were processed for scanning electron microscopy observation. In one case, a juvenile animal, whose ears were fixed within 4 hours of death, revealed that many sensory cells at the apex of the cochlear spiral were missing. In this case, the absence of outer hair cells would be compatible with overexposure to underwater noise, affecting the region which transduces the lowest frequencies of the pilot whales hearing spectrum. Perfusion of cochlea with fixative greatly improved preservation and enabled diagnostic imaging of the organ of Corti, even 30 hours after death. This finding supports adopting a routine protocol to detect the pathological legacy of noise overexposure in mass stranded cetaceans as a key to understanding the complex processes and implications that lie behind such stranding events.

Real‐time acoustic monitoring of the deep‐ocean environment

ESONET is a European Network of Excellence (NoE) associating 50 partners (research centres, universities, industrials and SMEs) from 14 countries: France, Germany, Italy, UK, Spain, Portugal, Greece, Belgium, Ireland, the Netherlands, Norway, Sweden, Bulgaria, and Turkey. More than 300 scientists and engineers will participate to its activities. The aim of the ESONET NoE is the lasting integration of European research on deep‐sea multidisciplinary observatories. ESONET is particularly sensitive on the effects of noise on marine organisms. Because our knowledge is still quite limited, ESONET is developing a Demonstration Mission, called LIDO, Listening to the Deep‐Ocean Environment, a research program that will help establishing a scientific base to allow (1) the real‐time automatic identification and classification of nonbiological and biological sounds, (2) the monitoring of marine organisms and population dynamics, (3) the assessment and control of the long term effects of anthropogenic sources on marin...

PAROTID CARCINOMA IN A FREE-RANGING CALIFORNIA SEA LION (ZALOPHUS CALIFORNIANUS)

Abstract A free-ranging juvenile California sea lion (Zalophus californianus) stranded on the coast of Vancouver, British Columbia, with signs of lethargy and emaciation in April 2016. An asymmetrical skull with a prominent superficial cervical lymph node was found on initial assessment. Fine-needle aspirates and biopsies of the lymph node were consistent with neoplasia and the animal was humanely euthanized and presented for necropsy. A metastatic parotid gland adenocarcinoma was diagnosed with regional lymph node and pulmonary metastases. Local invasion of contiguous skeletal muscle, bone, ear, and tonsils was extensive and likely accounted for the unilateral craniofacial deformity. Neoplasia of nonurogenital origin in juvenile California sea lions are reported infrequently. This is the first case of a parotid carcinoma in a California sea lion.

Parasites in the inner ear of harbour porpoise: cases from the North and Baltic Seas

Peribullar sinuses of harbour porpoises Phocoena phocoena are parasitized with high prevalence by the nematode Stenurus minor. The effect of S. minor on the hearing ability of this species is still undetermined. Here, we review the occurrence of S. minor in the inner ear of harbour porpoises recovered from strandings in the North and Baltic Seas. In particular, we present the results from ears collected in German and Danish waters from 2002 to 2016 and from Dutch waters from 2010 to 2016. While the prevalence of S. minor in pterygoid and peribullar sinuses and tympanic cavity was high in harbour porpoises (66.67% in our cases), its prevalence in the cochlea was rare. Only 1 case out of 129 analysed by either histology, electron microscopy or immunofluorescence showed the presence of a nematode parasite morphologically consistent with S. minor at the most basal portion of the right cochlea. This individual also had severe haemorrhage along the right cochlear spiral, which was likely caused by ectopic S. minor migration. Although this animal might have had impaired hearing in the right ear, it was otherwise in good body condition with evidence of recent feeding. These findings highlight the need to study the effect of parasites on hearing, and other pathological changes that might impair appropriate processing of acoustic information.

Description of Cochlear Morphology and Hair Cell Variation in the Beluga Whale

Environmental change and decreased ice cover in the Arctic make new areas accessible to humans and animals. It is important to understand how these changes impact marine mammals, such as beluga whales (Delphinapterus leucas Pallas, 1776). Hearing is crucial in the daily lives of cetaceans. Consequently, we need normal baselines to further understand how anthropogenic noise affects these animals. Relatively little is known about the inner ear morphology of belugas, particularly the organ of Corti, or hearing organ, found within the cochlea. The base of the cochlea encodes for high-frequency sounds, while low frequencies are detected in the apex. We showed differences between the apex, or centremost point of the cochlea, and the base, the region closest to the stapes. Our results showed that average outer hair cell density changed from 148 cells/mm in the apex to 117 cells/mm in the base. Cell width varied between the two regions, from 5.8 µm in the apex to 8.4 µm in the base. These results revealed variati...

Decalcifying Protocol of Odontocete Ear Samples with RDO

The study of the organ of Corti is essential to assess the impact of underwater noise on cetaceans. While classical histology techniques (including EDTA decalcification) have been previously considered, the process is time consuming and artifacts, probably directly deriving from the protocol, often appear and difficult the analysis. However, no matter the choice of the analysis technique, one of the challenging step after extraction and fixation of the samples is to decalcify the bone envelope to access the cochlea without damaging the soft tissues. Here, we propose to use a fast commercial decalcifier (RDO®). 103 ears from 12 different odontocetes species stranded in the Mediterranean, Spanish North Atlantic and North Sea have been used to precisely determine the decalcification time. Specifically, the species processed were: Phocoena phocoena (n=45), Stenella coeruleoalba (n=12), Stenella frontalis (n=12), Tursiops truncatus (n=13), Delphinus delphis (n=4), Kogia simus (n=3), Kogia breviceps (n=2), Glob...