Stroke is a complex and devastating neurological condition with limited treatment options. Brain edema is a serious complication of stroke. Early edema formation can significantly contribute to infarct formation and thus represents a promising target. Aquaporin (AQP) water channels contribute to water homeostasis by regulating water transport and are implicated in several disease pathways. At least 7 AQP subtypes have been identified in the rodent brain and the use of transgenic mice has greatly aided our understanding of their functions. AQP4, the most abundant channel in the brain, is up-regulated around the peri-infarct border in transient cerebral ischemia and AQP4 knockout mice demonstrate significantly reduced cerebral edema and improved neurological outcome. In models of vasogenic edema, brain swelling is more pronounced in AQP4-null mice than wild-type providing strong evidence of the dual role of AQP4 in the formation and resolution of both vasogenic and cytotoxic edema. AQP4 is co-localized with inwardly rectifying K+-channels (Kir4.1) and glial K+ uptake is attenuated in AQP4 knockout mice compared to wild-type, indicating some form of functional interaction. AQP4-null mice also exhibit a reduction in calcium signaling, suggesting that this channel may also be involved in triggering pathological downstream signaling events. Associations with the gap junction protein Cx43 possibly recapitulate its role in edema dissipation within the astroglial syncytium. Other roles ascribed to AQP4 include facilitation of astrocyte migration, glial scar formation, modulation of inflammation and signaling functions. Treatment of ischemic cerebral edema is based on the various mechanisms in which fluid content in different brain compartments can be modified. The identification of modulators and inhibitors of AQP4 offer new therapeutic avenues in the hope of reducing the extent of morbidity and mortality in stroke.
The axon myelin sheath is prone to injury associated with N-methyl-d-aspartate (NMDA)-type glutamate receptor activation but the source of glutamate in this context is unknown. Myelin damage results in permanent action potential loss and severe functional deficit in the white matter of the CNS, for example in ischemic stroke. Here, we show that in rats and mice, ischemic conditions trigger activation of myelinic NMDA receptors incorporating GluN2C/D subunits following release of axonal vesicular glutamate into the peri-axonal space under the myelin sheath. Glial sources of glutamate such as reverse transport did not contribute significantly to this phenomenon. We demonstrate selective myelin uptake and retention of a GluN2C/D NMDA receptor negative allosteric modulator that shields myelin from ischemic injury. The findings potentially support a rational approach toward a low-impact prophylactic therapy to protect patients at risk of stroke and other forms of excitotoxic injury.
Heterogeneous data collection in the marine environment has led to large gaps in our knowledge of marine species distributions. To fill these gaps, models calibrated on existing data may be used to predict species distributions in unsampled areas, given that available data are sufficiently representative. Our objective was to evaluate the feasibility of mapping cetacean densities across the entire Mediterranean Sea using models calibrated on available survey data and various environmental covariates. We aggregated 302,481 km of line transect survey effort conducted in the Mediterranean Sea within the past 20 years by many organisations. Survey coverage was highly heterogeneous geographically and seasonally: large data gaps were present in the eastern and southern Mediterranean and in non-summer months. We mapped the extent of interpolation versus extrapolation and the proportion of data nearby in environmental space when models calibrated on existing survey data were used for prediction across the entire Mediterranean Sea. Using model predictions to map cetacean densities in the eastern and southern Mediterranean, characterised by warmer, less productive waters, and more intense eddy activity, would lead to potentially unreliable extrapolations. We stress the need for systematic surveys of cetaceans in these environmentally unique Mediterranean waters, particularly in non-summer months.
1. Preservation of endangered species is now recognized as a relevant component of regional and global conservation actions achieved through the maintenance of the remaining populations in a favourable conservation status. The Mediterranean common dolphin (Delphinus delphis) is listed as an Endangered subpopulation in the International Union for Conservation of Nature Red List, with declining numbers in some of the areas where it has been studied for numerous years. Prey depletion, fisheries bycatch, pollution, health risks, and climate change are among the recognized threats that the species is facing in the region.2. The existing national, regional, and international legislation pertinent to Mediterranean countries should aid greater science-policy-management integration and support innovative research and monitoring towards effective conservation. The challenges inherent in studying the pelagic D. delphis should not preclude the use of long-term, year-round, multiplatform surveys, side by side with the latest molecular tools, which aid our understanding of its populations' genetic diversity, resistance to diseases, and resilience in a semi-enclosed fast-changing sea.3. Addressing the multiplicity of problems confronting the species requires collaborative effort at all levels to share and merge resources, data, and expertise more efficiently. In this review, we provide an overview of the current knowledge on the Mediterranean common dolphin, the main threats, and knowledge gaps that are priorities for addressing its conservation, while providing clear recommendations for effectively safeguarding the species and its habitat at both local and regional levels.
Objective To assess the perception of Maltese consumers regarding extended professional services for community pharmacists. Methods The self‐administered questionnaire developed by Wirth et al. was formulated into a concise questionnaire consisting of seven Likert scale statements focusing on extended professional services for community pharmacists including; longer pharmacy opening hours, pharmacist accessibility outside pharmacy opening hours, availability of a private consultation area, provision of diagnostic testing, keeping patient medication records, pharmacist–physician collaboration to manage chronic conditions and pharmacist prescribing. The questionnaire was distributed to 824 consumers recruited by random sampling during educational activities organised to promote the role of the community pharmacist in five localities in Malta. The importance given to each statement by the consumers was analysed. Key findings The consumers perceived pharmacist–physician collaboration in the management of chronic conditions (93%) and provision of diagnostic testing (92%) to be the most important extended professional services. Pharmacist prescribing (69%) and pharmacist accessibility outside pharmacy opening hours (68%) were perceived to be the least important. The percentage of consumers who perceived having a private consultation area in the pharmacy, keeping medication records and longer pharmacy opening hours as important was 87%, 83% and 81% respectively. Conclusions Maltese consumers perceive community pharmacist extended professional services as important, particularly pharmacist–physician collaboration in the management of chronic conditions and provision of diagnostic testing.
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