Alpha-linolenic omega-3 fatty acid for stroke protection: from brain preconditioning paradigm to nutrition

International audienceStroke is the third leading cause of death, due to its high incidence, theseverity of the insult, and lack of treatment options. The only therapeutic is restoration ofcerebral blood flow achieved by recombinant tissue plasminogen activator treatment,but only approximately 5% of patients receive it. In addition, therapeutics aimed atachieving neuroprotection by blocking the ischemic cascade, as identified in numerouspreclinical studies, failed in clinical trials. This failure in translation from experimentalmodels to clinical trials led to a re-evaluation of properties which would constitute the‘‘best-in class’’ therapeutics to be used against stroke. Given that neuroprotectionappears ineffective per se, an emerging direction is to identify therapies, probablycombinatorial in nature, which protect the whole neurovascular unit and target timedependentneurotoxic mechanisms. Molecules that activate complex cellular signalingcascades that render the brain resistant to subsequent ischemia, known aspreconditioners, offer a novel perspective in stroke protection. Preconditioning elicitscomplex endogenous neuroprotective responses that act by pleiotropic mechanisms toblock death pathways, promote survival pathways and increase resistance. In addition tochemical preconditioners, natural/endogenous compounds such as adenosine,glutamate, lysophospholipids, and omega-3 polyunsaturated fatty acids have beendemonstrated to be excellent preconditioners. Consequently, a major new concept inpreconditioning to combat stroke is introduced, which is preconditioning achievedthrough supplementation of an essential item in diet or as a nutraceutical. Severalepidemiologic studies suggested a beneficial effect of a seafood/omega-3-enriched dietin cerebral diseases, but the omega-3-induced protective mechanisms are still poorlyidentified. This review highlights how a-linolenic acid (ALA), the omega-3 polyunsaturatedfatty acid precursor, protects the brain from in vivo and in vitro models of stroke,thus potentially fulfilling the goal of identifying the ‘‘best-in class’’ therapeutics againststroke. Also described is the surprising pleiotric nature of ALA in protecting neurons,vasodilating brain arteries and stimulating neuroplasticity. Importantly, feasibility ofdelivery has been demonstrated, since ALA supplementation can be achieved throughmodification of the daily diet, for which prevention of stroke-induced mortality andcerebral damage has been confirmed. Therefore evaluating ALA as an interestingpreconditioner against stroke represents a novel and extremely relevant concept in thecontext of nutraceutical and functional food development

The nutraceutical potential of omega-3 alpha-linolenic acid in reducing the consequences of stroke

International audienceStroke is a worldwide major cause of mortality and morbidity. Preclinical studies have identified over 1000 molecules with brain-protective properties. More than 200 clinical trials have evaluated neuroprotective candidates for ischemic stroke yet, to date almost all failed, leading to a re-analysis of treatment strategies against stroke. An emerging view is to seek combinatory therapy, or discovering molecules able to stimulate multiple protective and regenerative mechanisms. A pertinent experimental approach to identify such candidates is the study of brain preconditioning, which refers to how the brain protects itself against ischemia and others stress-inducing stimuli. The recent discovery that nutrients like alpha-linolenic acid (ALA is an essential omega-3 polyunsaturated fatty acid required as part of our daily diet), may be an efficient brain preconditionner against stroke fosters the novel concept of brain preconditioning by nutraceuticals. This review stresses the underestimated role of nutrition in preventing and combating stroke. Although there is a consensus that increased consumption of salt, fatty foods and alcoholic beverages may promote pathologies like hypertension, obesity and alcoholism - all of which are well known risk factors of stroke - few risk factors are attributed to a deficiency in an essential nutrient in the diet. The ALA deficiency observed in the Western modern diets may itself constitute a risk factor. This review outlines how ALA supplementation by modification of the daily diet prevented mortality and cerebral damage in a rodent model of ischemic stroke. It also describes the pleiotropic ability of ALA to trigger responses that are multicellular, mechanistically diverse, resulting in neuronal protection, stimulation of neuroplasticity, and brain artery vasodilation. Overall, this review proposes a promising therapeutic opportunity by integrating a nutritional-based approach focusing on enriching the daily diet in ALA to prevent the devastating damage caused by stroke

Cruise ship pathologies in remote regions

Background: Navigations on cruise ships are rising and tend to spread to remote areas like polar regions. Our aim was to assess the prevalence of pathologies encountered on a cruise ship navigating in remote areas including Polar Seas. Materials and methods: A prospective observational, descriptive and cross-sectional study was conducted aboard a cruise ship with an overall capacity of 200–264 passengers and 140 crewmembers, sailing in remote areas as the Arctic Ocean and the Antarctic Peninsula over a period of 205 days. The database was built on all first consultations for passengers and crewmembers done by the onboard physician. Each symptom and diagnosis was coded according to the “International Classification of Primary Care, 2nd edition”. For statistical analysis, the quantitative data were expressed as mean ± standard deviation and qualitative data as percentages. The percentages were compared using a c2 test corrected according to the Yates’ method or by a Fisher test when appropriate. Results: A total of 446 diagnoses were studied on the 910 consultations originally included (13.7% of the people on board). The median age for the passengers and the crewmembers was respectively 68 (age ranging from 12 to 90) years and 31 (18–62) years. Likewise, the sex ratio (male/female) was 0.98 and 3.23. Infectious diseases were predominant (prevalence of 43.7%). Among them, respiratory infections were the most common and gastroenteritis seemed to be more frequent in passengers (prevalence of 11.5% vs. 5%, p = 0.10). Cutaneous pathologies were more frequent in crewmembers (prevalence of 26.6% vs. 18.7%, p = 0.04) and allergic dermatitis was the second most frequent in this group of patients (prevalence of 7.2%). Cardiovascular diseases, more common in passengers (p = 0.05), represented 4% of all diagnoses. Two cases of phlebitis, one stroke and one subacute heart failure were diagnosed. Among traumatic injuries, cutaneous traumas were the commonest (prevalence of 76.5%). Musculoskeletal traumas were more common in passengers (p = 0.04). An acute gastrointestinal haemorrhage required a medical evacuation from the Antarctic Peninsula. Conclusions: The physician should be prepared to face emergency cases by developing personal expertise specific to maritime medicine in remote areas. Highlighting the particularity of cases handled in remote areas, our results should also pave the way of the development of medical protocols for ships lacking physician

Tackling issues in the path toward clinical translation in brain conditioning: Potential offered by nutraceuticals

International audienceBrief periods of ischemia have been shown in many experimental setups to provide tolerance against ischemia in multiple organs including the brain, when administered before (preconditioning) or even after (postconditioning) the normally lethal ischemia. In addition to these so-called ischemic conditionings, many pharmacological and natural agents (e.g., chemicals and nutraceuticals) can also act as potent pre-and post-conditioners. Deriving from the original concept of ischemic preconditioning, these various conditioning paradigms may be promising as clinical-stage therapies for prevention of ischemic-related injury, especially stroke. As no proven experimentally identified strategy has translated into clinical success, the experimental induction of neuroprotection using these various conditioning paradigms has raised several questions, even before considering translation to clinical studies in humans. The first aim of the review is to consider key questions on preclinical studies of pre-or post-conditioning modalities including those induced by chemical or nutraceuticals. Second, we make the argument that several key issues can be addressed by a novel concept, nutraceutical preconditioning. Specifically, α-linolenic acid (alpha-linolenic acid [ALA] an omega-3 polyunsaturated fatty acid), contained in plant-derived edible products, is essential in the daily diet, and a body of work has identified ALA as a pre-and post-conditioner of the brain. Nutritional intervention and functional food development are an emerging direction for preventing stroke damage, offering the potential to improving clinical outcomes through activation of the endogenous protective mechanisms known collectively as conditioning

Netvibes, un tout en un numérique

Netvibes est un outil facile à utiliser pour rassembler l’éventail des ressources d’une bibliothèque. C’est aussi une carte heuristique utile pour évaluer une politique documentaire, en identifiant soit les inclinaisons trop prononcées, soit les lacunes dans le développement des collections. Entrons dans la danse des widgets

An acute coronary syndrome in Antarctica

Cruise tourism to Antarctica is constantly growing. Passengers and crewmembers may experience illnesses or injuries while traveling to remote areas with harsh weather conditions from where prompt evacuation is mostly unavailable. While a small explorer ship was at Wilhelmina bay (64°39’ South and 62°08’ West) in the Antarctic Peninsula, a 73-year-old male passenger presented with acute chest pain after two short excursions off the vessel in cold weather conditions. He was treated on board and remained clinically stable until the ship reached Ushuaia at the end of the cruise which was 5 days after the symptoms onset.

Conditioning Medicine A new pharmacological preconditioning-based target: from drosophila to kidney transplantation

International audienceOne of the biggest challenges in medicine is to dampen the pathophysiological stress induced by an episode of ischemia. Such stress, due to various pathological or clinical situations, follows a restriction in blood and oxygen supply to tissue, causing a shortage of oxygen and nutrients that are required for cellular metabolism. Ischemia can cause irreversible damage to target tissue leading to a poor physiological recovery outcome for the patient. Contrariwise, preconditioning by brief periods of ischemia has been shown in multiple organs to confer tolerance against subsequent normally lethal ischemia. By definition, preconditioning of organs must be applied preemptively. This limits the applicability of preconditioning in clinical situations, which arise unpredictably, such as myocardial infarction and stroke. There are, however, clinical situations that arise as a result of ischemia-reperfusion injury, which can be anticipated, and are therefore adequate candidates for preconditioning. Organ and more particularly kidney transplantation, the optimal treatment for suitable patients with end stage renal disease (ESRD), is a predictable surgery that permits the use of preconditioning protocols to prepare the organ for subsequent ischemic/reperfusion stress. It therefore seems crucial to develop appropriate preconditioning protocols against ischemia that will occur under transplantation conditions, which up to now mainly referred to mechanical ischemic preconditioning that triggers innate responses. It is not known if preconditioning has to be applied to the donor, the recipient, or both. No drug/target pair has been envisioned and validated in the clinic. Options for identifying new target/drug pairs involve the use of model animals, such as drosophila, in which some physiological pathways, such as the management of oxygen, are highly conserved across evolution. Oxygen is the universal element of life existence on earth. In this review we focus on a very specific pathway of pharmacological preconditioning identified in drosophila that was successfully transferred to mammalian models that has potential application in human health. Very few mechanisms identified in these model animals have been translated to an upper evolutionary level. This review highlights the commonality between oxygen regulation between diverse animals

Le rôle majeur du canal potassique TREK-1 dans la protection neuronale induite par les oméga-3

International audienceThe nutritional interest of polyunsaturated fatty acids from omega-3, that are mainly present in vegetal and fish oils is now validated by the scientific community. Their beneficial effects have first been reported in coronary heart diseases. Many neurological and chronic diseases are often related to deficiencies in omega-3 and omega-6 and their derivatives. Polyunsaturated fatty acids from omega-3 family are essential to brain growth and neuronal preserving (foetuses, children, old people) as well as visual and cognitive functions. They are recently considered as factors of improvement in some mental diseases. Today, polyunsaturated fatty acids could play a key role in the prevention and/or or the treatment of cerebral diseases. With the development of in vitro and in vivo experimental models, it is now possible to demonstrate the omega-3-induced neuronal protection against major pathologies such as epileptic seizures and cerebral ischemia. The molecular mechanism of neuronal protection induced by omega-3 is now clarified. The omega-3 target would be a potassium channel, TREK-1, which belongs to the new family of 2-P domain potassium channels (K-2P). The discovery of the physiopathological role of these K-2P channels can represent an important therapeutical challenge not only in cerebrovascular diseases, but also in psychiatry.Les acides gras polyinsaturés (AGPI), incorporés dans les phospholipides membranaires sont desconstituants structuraux fondamentaux du système nerveux central (SNC) dont la teneur conditionnele fonctionnement des cellules neuronales. Ils représentent environ 20 %de la matière sèchecérébrale et sont constitués des familles oméga-3 (n-3) et oméga-6 (n-6). Les acides grasprécurseurs de ces deux familles (acide alphalinolénique et acide linoléique) sont trouvés enquantités appréciables dans certaines huiles végétales (colza, noix et soja) et sont considéréscomme des acides gras essentiels. Ne pouvant pas être synthétisés de novo par l’homme et lesanimaux, leur apport ne peut se faire que par l’alimentation. L’acide alphalinolénique (ALA,18 :3n-3), précurseur des longues chaînes oméga-3, peut être transformé par l’homme en dérivésà longues chaînes (LC-n-3), dont les plus importants sont les acides eicosapentaénoïque (EPA,20:5n-3) et docosahexanoïque (DHA, 22:6n-3), qui peuvent aussi être apportés par la consommationde poissons gras. L’acide linoléique (LA, 18:2n-6), précurseur des oméga-6 est transformé parl’homme en acide arachidonique (AA, 20:4n-6), LC-n-6 que l’on trouve aussi dans les viandesanimales terrestres. Un déséquilibre dans le rapport LA/ALA dans l’apport alimentaire (optimal auxalentours de 5) est source de déséquilibres métaboliques et peut avoir de profondes répercussionssur divers processus physiologique

La tolérance cérébrale : un choix prometteur vers de nouvelles thérapies contre les maladies neurologiques

International audienceIschemia and seizures are common diseases that result in neuronal death. To-date, there are no available treatments to block or reverse neuronal death pathways in patients who suffer from these diseases. All drugs that have been shown to be neuroprotective in animal models have failed in human trials. Therefore, the potential of preventative strategies for therapy is increasingly explored. Experimental studies have demonstrated that a brief cerebral ischemic insult, that is not harmful by itself, results in a temporary protective adaptation in the brain against a subsequent ischemic episode that would otherwise be lethal. This process, termed ischemic preconditioning, has been confirmed in different models of cerebral ischemia. A similar phenomenon observed after a mild epileptic insult conferred a transitory tolerance to a subsequent epileptic episode. This process is termed epileptic tolerance. Other stresses, like hyperthermia or spreading depression, also enhanced brain resistance to detrimental effects of ischemic or epileptic injury. Recently, a cross tolerance between ischemia and epilepsy has been reported. Also, some retrospective studies in humans suggest that endogenous ischemic preconditioning exists in the brain. Altogether these insights of brain tolerance point to the future discovery of potentially useful targets for acute neuroprotection as well as preventive therapy.Les accidents ischémiques et les crises épileptiques font partie des causes majeures de mort neuronale. Malgré les nombreuses recherches sur la neuroprotection et la découverte de nouvelles molécules capables de bloquer certains des événements délétères chez l’animal, peu de traitements sont disponibles pour lutter contre la mort neuronale induite par ces maladies. Le plus efficace reste le traitement thrombolytique en phase aiguë des accidents ischémiques cérébraux, qui ne peut toutefois être administré que chez une très faible population de patients. La prévention visant à réduire l’incidence des facteurs de risque reste donc la principale stratégie thérapeutique. La tolérance cérébrale est un phénomène endogène reposant sur l’induction préventive de la résistance neuronale. La compréhension de ses mécanismes permettrait d’identifier de nouvelles cibles thérapeutiques. Les inducteurs pharmacologiques de la tolérance cérébrale devraient conduire à la même neuroprotection et à la mise en œuvre de nouvelles thérapeutique