Dysregulation of extracellular potassium distinguishes healthy ageing from neurodegeneration.

Progressive neuronal loss is a hallmark feature distinguishing neurodegenerative diseases from normal ageing. However, the underlying mechanisms remain unknown. Extracellular K+ homeostasis is a potential mediator of neuronal injury as K+ elevations increase excitatory activity. The dysregulation of extracellular K+ and potassium channel expressions during neurodegeneration could contribute to this distinction. Here we measured the cortical extracellular K+ concentration ([K+]e) in awake wild-type mice as well as murine models of neurodegeneration using K+-sensitive microelectrodes. Unexpectedly, aged wild-type mice exhibited significantly lower cortical [K+]e than young mice. In contrast, cortical [K+]e was consistently elevated in Alzheimer's disease (APP/PS1), amyotrophic lateral sclerosis (ALS) (SOD1G93A) and Huntington's disease (R6/2) models. Cortical resting [K+]e correlated inversely with neuronal density and the [K+]e buffering rate but correlated positively with the predicted neuronal firing rate. Screening of astrocyte-selective genomic datasets revealed a number of potassium channel genes that were downregulated in these disease models but not in normal ageing. In particular, the inwardly rectifying potassium channel Kcnj10 was downregulated in ALS and Huntington's disease models but not in normal ageing, while Fxyd1 and Slc1a3, each of which acts as a negative regulator of potassium uptake, were each upregulated by astrocytes in both Alzheimer's disease and ALS models. Chronic elevation of [K+]e in response to changes in gene expression and the attendant neuronal hyperexcitability may drive the neuronal loss characteristic of these neurodegenerative diseases. These observations suggest that the dysregulation of extracellular K+ homeostasis in a number of neurodegenerative diseases could be due to aberrant astrocytic K+ buffering and as such, highlight a fundamental role for glial dysfunction in neurodegeneration.

Citalopram in the treatment of elderly chronic heart failure combined with depression: A systematic review and meta-analysis.

Background: Depression is an independent factor to predict the hospitalization and mortality in the chronic HF patients. Citalopram is known as an effective drug for depression treatment. Currently, there is no specific recommendation in the HF guidelines for the treatment of psychological comorbidity. In recent years, many studies have shown that the citalopram may be safe in treating of chronic HF with depression. Objective: To evaluate the efficacy and safety of the citalopram in the treatment of elderly chronic HF combined with depression. Methods: PubMed, EMBASE, Cochrane, Web of Science, CNKI, VIP, CBM, and Wanfang were searched from their inception to May 2022. In the treatment of elderly chronic HF combined with depression, randomized controlled studies of the citalopram were included. Independent screening and extraction of data information were conducted by two researchers, and the quality was assessed by the Cochrane bias risk assessment tool. Review manager 5.4.1 was employed for statistical analysis. Results: The results of meta-analysis prove that the citalopram treatment for depressed patients with chronic HF has a benefit for HAMD-24 (MD: -8.51, 95% CI: -10.15 to -6.88) and LVEF (MD: 2.42, 95% CI: 0.51 to 4.33). Moreover, the score of GDS decreases, and NT-proBNP (MD: -537.78, 95% CI: -718.03 to -357.54) is improved. However, the comparison with the control group indicates that there is no good effect on HAMD-17 (MD: -5.14, 95% CI: -11.60 to 1.32), MADRS (MD: -1.57, 95% CI: -3.47 to 0.32) and LVEDD (MD: -1.45, 95% CI: -3.65 to -0.76). No obvious adverse drug reactions were observed. Conclusion: Citalopram treatment for depressed patients with chronic HF has a positive effect on LVEF and NT-proBNP. It can alleviate HAMD-24 and GDS, but the relative benefits for LVEDD, HAMD-17 and MADRS still need to be verified.Systematic Review Registration: PROSPERO [CRD42021289917].

The effect of intensive family-centered health education on the awareness rate, diagnosis, and treatment of post-stroke depression in community families.

OBJECTIVE: To investigate the effects of intensive family-centered health education on the awareness rate, diagnosis, and treatment of post-stroke depression (PSD) in community families. METHODS: Elderly patients (60-90 years) from 20 community service centers affiliated with the Department of Neurology and the Medical Association of Tongling Municipal Hospital who had been diagnosed with stroke between January 2017 and June 2020 were screened using the hospital and community electronic medical record system. In this randomized cluster trial, 119 patients from 10 communities were assigned as the control group and received routine community treatment, while 126 patients from the other 10 communities were assigned as the experimental group and received routine treatment plus family-centered intensive health education. After 12 months of medical intervention, the assessment of PSD in the two groups was performed by a neurologist and a psychiatrist, both blind to the study design, using the Hamilton Rating Scale for Depression. RESULTS: The awareness rates of the causes, clinical manifestations, treatment plan, and family care of PSD in the experimental group were 88.89, 91.30, 93.65, and 92.06%, respectively. In the control group, the awareness rates of these parameters were 72.27, 69.75, 71.43, and 65.55%, respectively, and the differences between the two groups were statistically significant (P < 0.05). In the experimental group, the rates of PSD diagnosis, prompt medical attendance, drug treatment compliance, and psychotherapeutic treatment compliance were 27.78, 22.22, 18.25, and 11.90%, respectively. In the control group, the rates of these parameters were 13.79, 6.03, 3.48, and 1.72%, respectively, and the differences between the two groups were statistically significant (P < 0.05). CONCLUSION: Intensive family-centered health education can improve the level of knowledge of PSD in the community, promote the timely treatment and diagnosis of PSD in patients, and improve the compliance rates of drug therapy and psychotherapy, so this is worthy of promotion.

An evaluation of the efficacy and safety of thrombolysis in patients with wake-up stroke using the combination of inflammatory factors Interleukin-6 and C-reactive protein with multi-mode magnetic resonance imaging.

OBJECTIVE: To explore the efficacy and safety of using thrombolysis in patients with wake-up stroke (WUS). METHODS: The serum IL-6 and hs-CRP levels of the patients in both the experimental group and the standard group were measured before thrombolysis and at 1 and 24 h afterwards. National Institute of Health Stroke Scale (NIHHS) scores were also recorded at the same time points as well as at 10 and 90 d after thrombolysis, and modified Rankin Scale (mRS) scores were calculated before thrombolysis and at 10 and 90 d afterwards. The differences in all these observations before and after thrombolysis were then investigated. RESULTS: (1) The levels of serum IL-6 and hs-CRP in the experimental group and the standard group were higher than those in the healthy control group before thrombolysis (P < 0.05), indicating that higher levels of hs-CRP and IL-6 are risk factors for WUS (P < 0.05). (2) There were no significant differences in the serum hs-CRP and IL-6 levels of the patients in the experimental and standard groups before thrombolysis (P > 0.05). (3) The serum IL-6 and hs-CRP levels were positively correlated with the NIHHS scores in both the experimental group and the standard group (P < 0.05), and they correlated with the mRS scores at 90 d. CONCLUSIONS: Interleukin-6 and hs-CRP can be used as biological indicators of inflammatory injury and diagnosis of stroke, and the combined detection of IL-6 and hs-CRP is of importance in predicting a deterioration in stroke patients.

Imaging characteristics, misdiagnosis and microsurgical outcomes of patients with spinal dural arteriovenous fistula: a retrospective study of 32 patients.

Background: Spinal dural arteriovenous fistula (SDAVF) is an extremely rare spinal vascular malformation. As SDAVF exhibits no specific clinical manifestations nor diverse imaging results, it is easily misdiagnosed, resulting in delayed treatment and irreversible neurological damage. Most patients were initially misdiagnosed, but there were few reports on reducing misdiagnosis. Methods: A total of 32 consecutive patients, who presented to our institution (Shanghai Deji Hospital) with SDAVF between June 2013 and January 2016 were retrospectively analyzed. Data were collected on demographics, clinical presentation, imaging findings, follow-up, and clinical outcomes. The Aminoff-Logue scale (ALS) was used to assess clinical outcomes. Results: Of the 32 enrolled patients (3 females, mean age 59.1±3.8 years), 23 patients (71.9%) were misdiagnosed as acute myelitis (11 patients), intramedullary tumors (6 patients), lumbar disc herniation (4 patients), and other conditions (2 patients). All patients underwent surgical procedures under electrophysiological monitoring. Fistulas were found in all 32 patients and were successfully occluded. The mean follow-up period was 19.22±8.21 months (ranging from 2 weeks to 30 months). One year later, 20 patients underwent magnetic resonance imaging (MRI), and 14 showed no T2 edema, and the edema was relieved in 6 patients. A total of 10 patients underwent enhancement MRI and no enhancement signs were detected. Among the 27 patients with long-time follow-up, the fistula had no residual or recurrence, 21 patients showed decreased ALS scores (P<0.05). Six patients exhibited nonsignificant improvement. No aggravating patient was found. Prognosis differed significantly between patients with ALS <6 and those with ALS ≥6 (P<0.05). Conclusions: Spinal angiography should be performed with full intubation, and microcatheter angiography can reduce misdiagnosis. SDAVF must be differentiated from acute myelitis, intramedullary tumor, and other spinal vascular malformations. Microsurgical treatment is effective with a low recurrence rate.

Atrial Fibrillation and Depression: A Bibliometric Analysis From 2001 to 2021.

BACKGROUND: The control of diseases related to atrial fibrillation (AF) may reduce the occurrence of AF, delay progression, and reduce complications, which is beneficial to the prevention and treatment of AF. An increasing number of studies have shown that AF is associated with depression. However, to date, there has not been a bibliometric analysis to examine this field systematically. Our study aimed to visualize the publications to determine the hotspots and frontiers in research on AF and depression and provide guidance and reference for further study. METHODS: Publications about AF and depression between 2001 and 2021 were retrieved from the Web of Science Core Collection (WOSCC) database. CiteSpace 5.8. R1, VOSviewer 1.6.16, and Excel 2019 software tools were used to conduct this bibliometric study. RESULTS: In total, 159 articles and reviews were analyzed. The number of publications has been increased sharply since 2018. David D. McManus had the largest number of publications. The most prolific country was the USA with 54 publications but the centrality was <0.1. The most prolific institution was Northeastern University. Three clusters were formed based on keywords: The first cluster was composed of atrial fibrillation, depression, anxiety, symptoms, ablation, and quality of life, et al. The second cluster were risk, prevalence, mortality, heart failure, association, et al. While the third cluster included anticoagulation, impact, stroke, management, warfarin, et al. After 2019, stroke and prediction are the keywords with strongest citation bursts. CONCLUSION: Research on AF and depression is in its infancy. Cooperation and exchanges between countries and institutions must be strengthened in the future. The effect of depression on prevalence and mortality in AF, depression on ablation in AF, and impact of depression on anticoagulation treatment in AF have been the focus of current research. Stroke prevention (including anticoagulant therapy) is the research frontier, which may still be the focus of research in the future.

Comparative genomics provides insights into the aquatic adaptations of mammals.

The ancestors of marine mammals once roamed the land and independently committed to an aquatic lifestyle. These macroevolutionary transitions have intrigued scientists for centuries. Here, we generated high-quality genome assemblies of 17 marine mammals (11 cetaceans and six pinnipeds), including eight assemblies at the chromosome level. Incorporating previously published data, we reconstructed the marine mammal phylogeny and population histories and identified numerous idiosyncratic and convergent genomic variations that possibly contributed to the transition from land to water in marine mammal lineages. Genes associated with the formation of blubber (NFIA), vascular development (SEMA3E), and heat production by brown adipose tissue (UCP1) had unique changes that may contribute to marine mammal thermoregulation. We also observed many lineage-specific changes in the marine mammals, including genes associated with deep diving and navigation. Our study advances understanding of the timing, pattern, and molecular changes associated with the evolution of mammalian lineages adapting to aquatic life.

Comparison of different sequencing strategies for assembling chromosome-level genomes of extremophiles with variable GC content.

In this study, six bacterial isolates with variable GC, including Escherichia coli as mesophilic reference strain, were selected to compare hybrid assembly strategies based on next-generation sequencing (NGS) of short reads, single-tube long-fragment reads (stLFR) sequencing, and Oxford Nanopore Technologies (ONT) sequencing platforms. We obtained the complete genomes using the hybrid assembler Unicycler based on the NGS and ONT reads; others were de novo assembled using NGS, stLFR, and ONT reads by using different strategies. The contiguity, accuracy, completeness, sequencing costs, and DNA material requirements of the investigated strategies were compared systematically. Although all sequencing data could be assembled into accurate whole-genome sequences, the stLFR sequencing data yield a scaffold with more contiguity with more completeness of gene function than NGS sequencing assemblies. Our research provides a low-cost chromosome-level genome assembly strategy for large-scale sequencing of extremophile genomes with different GC contents.

Draft Genomes and Comparative Analysis of Seven Mangrove Rhizosphere-Associated Fungi Isolated From Kandelia obovata and Acanthus ilicifolius.

Mangroves are one of the most productive and biologically diverse ecosystems, with unique plants, animals, and microorganisms adapted to the harsh coastal environments. Although fungi are widely distributed in the mangrove ecosystem and they are playing an important role in the decomposition of organic matter, their genomic profiles are still poorly understood. In this study, we isolated seven Ascomycota fungi (Westerdykella dispersa F012, Trichoderma lixii F014, Aspergillus tubingensis F023, Penicillium brefeldianum F032, Neoroussoella solani F033, Talaromyces fuscoviridis F034, and Arthrinium marii F035) from rhizospheres of two mangroves of Kandelia obovata and Acanthus ilicifolius. We sequenced and assembled the whole genome of these fungi, resulting in size ranging from 29 to 48 Mb, while contig N50 from 112 to 833 Kb. We generated six novel fungi genomes except A. tubingensis, and the gene completeness and genome completeness of all seven genomes are higher than 94%. Comparing with non-mangrove fungi, we found Carbohydrate-Binding Modules (CBM32), a subfamily of carbohydrate active enzymes, only detected in two mangrove fungi. Another two subfamilies, Glycoside Hydrolases (GH6) and Polysaccharide Lyases (PL4), were significantly different in gene copy number between K. obovata and A. ilicifolius rhizospheres (P-value 0.041 for GH6, 0.047 for PL4). These findings may indicate an important influence of mangrove environments or hosts on the ability of decomposition in rhizosphere fungi. Secondary metabolite biosynthesis gene clusters were detected and we found the mangrove fungi averagely contain 18 Type I Polyketide (t1pks) synthase, which was significantly higher than 13 in non-mangrove fungi (P-value 0.048), suggesting their potential roles in producing bioactive compounds that important for fungi development and ecology. We reported seven mangrove-associated fungal genomes in this study and compared their carbohydrate active enzymes and secondary metabolites (SM) genes with those of non-mangrove fungi, and the results suggest that there are differences in genetic information among fungi in different habitats.

The White-Spotted Bamboo Shark Genome Reveals Chromosome Rearrangements and Fast-Evolving Immune Genes of Cartilaginous Fish.

Chondrichthyan (cartilaginous fish) occupies a key phylogenetic position and is important for investigating evolutionary processes of vertebrates. However, limited whole genomes impede our in-depth knowledge of important issues such as chromosome evolution and immunity. Here, we report the chromosome-level genome of white-spotted bamboo shark. Combing it with other shark genomes, we reconstructed 16 ancestral chromosomes of bamboo shark and illustrate a dynamic chromosome rearrangement process. We found that genes on 13 fast-evolving chromosomes can be enriched in immune-related pathways. And two chromosomes contain important genes that can be used to develop single-chain antibodies, which were shown to have high affinity to human disease markers by using enzyme-linked immunosorbent assay. We also found three bone formation-related genes were lost due to chromosome rearrangements. Our study highlights the importance of chromosome rearrangements, providing resources for understanding of cartilaginous fish diversification and potential application of single-chain antibodies.

The Chromosome Level Genome and Genome-wide Association Study for the Agronomic Traits of Panax Notoginseng.

The Chinese ginseng Panax notoginseng is a domesticated herb with significant medicinal and economic value. Here we report a chromosome-level P. notoginseng genome assembly with a high (∼79%) repetitive sequence content. The juxtaposition with the widely distributed, closely related Korean ginseng (Panax ginseng) genome revealed contraction of plant defense genes (in particular R-genes) in the P. notoginseng genome. We also investigated the reasons for the larger genome size of Panax species, revealing contributions from two Panax-specific whole-genome duplication events and transposable element expansion. Transcriptome data and comparative genome analysis revealed the candidate genes involved in the ginsenoside synthesis pathway. We also performed a genome-wide association study on 240 cultivated P. notoginseng individuals and identified the associated genes with dry root weight (63 genes) and stem thickness (168 genes). The P. notoginseng genome represents a critical step toward harnessing the full potential of an economically important and enigmatic plant.

An ocular glymphatic clearance system removes ß-amyloid from the rodent eye.

Despite high metabolic activity, the retina and optic nerve head lack traditional lymphatic drainage. We here identified an ocular glymphatic clearance route for fluid and wastes via the proximal optic nerve in rodents. ß-amyloid (Aß) was cleared from the retina and vitreous via a pathway dependent on glial water channel aquaporin-4 (AQP4) and driven by the ocular-cranial pressure difference. After traversing the lamina barrier, intra-axonal Aß was cleared via the perivenous space and subsequently drained to lymphatic vessels. Light-induced pupil constriction enhanced efflux, whereas atropine or raising intracranial pressure blocked efflux. In two distinct murine models of glaucoma, Aß leaked from the eye via defects in the lamina barrier instead of directional axonal efflux. The results suggest that, in rodents, the removal of fluid and metabolites from the intraocular space occurs through a glymphatic pathway that might be impaired in glaucoma.

Comparative Plastome Analysis of Root- and Stem-Feeding Parasites of Santalales Untangle the Footprints of Feeding Mode and Lifestyle Transitions.

In plants, parasitism triggers the reductive evolution of plastid genomes (plastomes). To disentangle the molecular evolutionary associations between feeding on other plants below- or aboveground and general transitions from facultative to obligate parasitism, we analyzed 34 complete plastomes of autotrophic, root- and stem-feeding hemiparasitic, and holoparasitic Santalales. We observed inexplicable losses of housekeeping genes and tRNAs in hemiparasites and dramatic genomic reconfiguration in holoparasitic Balanophoraceae, whose plastomes have exceptionally low GC contents. Genomic changes are related primarily to the evolution of hemi- or holoparasitism, whereas the transition from a root- to a stem-feeding mode plays no major role. In contrast, the rate of molecular evolution accelerates in a stepwise manner from autotrophs to root- and then stem-feeding parasites. Already the ancestral transition to root-parasitism coincides with a relaxation of selection in plastomes. Another significant selectional shift in plastid genes occurs as stem-feeders evolve, suggesting that this derived form coincides with trophic specialization despite the retention of photosynthetic capacity. Parasitic Santalales fill a gap in our understanding of parasitism-associated plastome degeneration. We reveal that lifestyle-genome associations unfold interdependently over trophic specialization and feeding mode transitions, where holoparasitic Balanophoraceae provide a system for exploring the functional realms of plastomes.

Chromosome-Level Comprehensive Genome of Mangrove Sediment-Derived Fungus Penicillium variabile HXQ-H-1.

Penicillium is an ascomycetous genus widely distributed in the natural environment and is one of the dominant fungi involved in the decomposition of mangroves, which can produce a variety of antitumor compounds and bioactive substances. However, in mangrove ecosystems there is no complete genome in this genus. In this study, we isolated a fungus strain named Penicillium variabile HXQ-H-1 from coast mangrove (Fujian Province, China). We generated a chromosome-level genome with total size of 33.32 Mb, scaffold N50 of 5.23 Mb and contig N50 of 96.74 kb. Additionally, we anchored about 95.91% assembly sequences into the longest seven scaffolds, and predicted 10,622 protein-coding genes, in which 99.66% could be annotated by eight protein databases. The secondary metabolites analysis reveals the strain has various gene clusters involving polyketide synthase (PKS), non-ribosomal peptide synthetase (NRPS) and terpene synthase that may have a largely capacity of biotechnological potential. Comparison genome analysis between Penicillium variabile and Talaromyces islandicus reveals a small difference in the total number of genes, whereas HXQ-H-1 has a higher gene number with COG functional annotation. Evolutionary relationship of Penicillum based on genome-wide data was carried out for the first time, showing the strain HXQ-H-1 is closely related to Talaromyces islandicus. This genomic resource may provide a new resource for development of novel bioactive antibiotics, drug candidates and precursors in Penicillium variabile.

A chromosome-level assembly of the Atlantic herring genome-detection of a supergene and other signals of selection.

The Atlantic herring is a model species for exploring the genetic basis for ecological adaptation, due to its huge population size and extremely low genetic differentiation at selectively neutral loci. However, such studies have so far been hampered because of a highly fragmented genome assembly. Here, we deliver a chromosome-level genome assembly based on a hybrid approach combining a de novo Pacific Biosciences (PacBio) assembly with Hi-C-supported scaffolding. The assembly comprises 26 autosomes with sizes ranging from 12.4 to 33.1 Mb and a total size, in chromosomes, of 726 Mb, which has been corroborated by a high-resolution linkage map. A comparison between the herring genome assembly with other high-quality assemblies from bony fishes revealed few inter-chromosomal but frequent intra-chromosomal rearrangements. The improved assembly facilitates analysis of previously intractable large-scale structural variation, allowing, for example, the detection of a 7.8-Mb inversion on Chromosome 12 underlying ecological adaptation. This supergene shows strong genetic differentiation between populations. The chromosome-based assembly also markedly improves the interpretation of previously detected signals of selection, allowing us to reveal hundreds of independent loci associated with ecological adaptation.

Resequencing 545 ginkgo genomes across the world reveals the evolutionary history of the living fossil.

As Charles Darwin anticipated, living fossils provide excellent opportunities to study evolutionary questions related to extinction, competition, and adaptation. Ginkgo (Ginkgo biloba L.) is one of the oldest living plants and a fascinating example of how people have saved a species from extinction and assisted its resurgence. By resequencing 545 genomes of ginkgo trees sampled from 51 populations across the world, we identify three refugia in China and detect multiple cycles of population expansion and reduction along with glacial admixture between relict populations in the southwestern and southern refugia. We demonstrate multiple anthropogenic introductions of ginkgo from eastern China into different continents. Further analyses reveal bioclimatic variables that have affected the geographic distribution of ginkgo and the role of natural selection in ginkgo's adaptation and resilience. These investigations provide insights into the evolutionary history of ginkgo trees and valuable genomic resources for further addressing various questions involving living fossil species.

Cortex-wide Changes in Extracellular Potassium Ions Parallel Brain State Transitions in Awake Behaving Mice.

Brain state fluctuations modulate sensory processing, but the factors governing state-dependent neural activity remain unclear. Here, we tracked the dynamics of cortical extracellular K+ concentrations ([K+]o) during awake state transitions and manipulated [K+]o in slices, during visual processing, and during skilled motor execution. When mice transitioned from quiescence to locomotion, [K+]o increased by 0.6-1.0 mM in all cortical areas analyzed, and this preceded locomotion by 1 s. Emulating the state-dependent [K+]o increase in cortical slices caused neuronal depolarization and enhanced input-output transformation. In vivo, locomotion increased the gain of visually evoked responses in layer 2/3 of visual cortex; this effect was recreated by imposing a [K+]o increase. Elevating [K+]o in the motor cortex increased movement-induced neuronal spiking in layer 5 and improved motor performance. Thus, [K+]o increases in a cortex-wide state-dependent manner, and this [K+]o increase affects both sensory and motor processing through the dynamic modulation of neural activity.

A survey of the sperm whale (Physeter catodon) commensal microbiome.

BACKGROUND: Mammalian commensal microbiota play important roles in the health of its host. In comparison to terrestrial mammals, commensal microbiota of marine mammals is mainly focused on the composition and function of skin and gut microbiota, with less attention paid to the health impact of bacteria and viruses. Previous studies on sperm whales (Physeter catodon) have affirmed their important phylogenetic position; however, studies on their commensal microbiota have not been published, due to difficulty in sample collection. METHODS: Here, we sequenced the metagenomes of blood, muscle and fecal samples from a stranded sperm whale using the BGISEQ-500 platform. We compared the diversity and abundance of microbiomes from three different tissues and tried to search pathogenic bacterial and virulence genes probably related to the health of the sperm whale. We also performed 16S rDNA sequencing of the fecal sample to compare to published gut metagenome data from other marine mammals. RESULTS: Our results demonstrated notable differences in species richness and abundance in the three samples. Extensive bacteria, including Enterococcus faecium, Fusobacterium nucleatum, Pseudomonas aeruginosa, Streptococcus anginosus, Streptococcus pneumoniae, and Streptococcus suis, and five toxigenic Clostridium species usually associated with infection, were found in the three samples. We also found the taxa composition of sperm whale gut microbiota was similar to that of other whales, suggesting co-evolution with its host. This study is the first report of the sperm whale gut microbiome, and provides a foundation for the pathogen detection and health assessment of the sperm whale.

Adrenergic receptor antagonism induces neuroprotection and facilitates recovery from acute ischemic stroke.

Spontaneous waves of cortical spreading depolarization (CSD) are induced in the setting of acute focal ischemia. CSD is linked to a sharp increase of extracellular K+ that induces a long-lasting suppression of neural activity. Furthermore, CSD induces secondary irreversible damage in the ischemic brain, suggesting that K+ homeostasis might constitute a therapeutic strategy in ischemic stroke. Here we report that adrenergic receptor (AdR) antagonism accelerates normalization of extracellular K+, resulting in faster recovery of neural activity after photothrombotic stroke. Remarkably, systemic adrenergic blockade before or after stroke facilitated functional motor recovery and reduced infarct volume, paralleling the preservation of the water channel aquaporin-4 in astrocytes. Our observations suggest that AdR blockers promote cerebrospinal fluid exchange and rapid extracellular K+ clearance, representing a potent potential intervention for acute stroke.