Biology subjects

Yasuda, S.

Publications and source records attributed to Yasuda, S..

14 recordsLinked to original sources

bioRxiv2026

Inosine Triphosphate Pyrophosphatase as a Candidate Associated with White Matter Abnormalities in Chronic Heart Failure

Background: White matter hyperintensities (WMHs) are common with normal brain aging and frequently observed also in chronic heart failure (CHF). However, the relationship between CHF and white matter abnormalities and the biological factors remain unclear. We investigated WMH and associated white matter microstructural changes, such as fractional anisotropy (FA), in CHF and explored candidate molecular factors. Methods: We conducted a longitudinal prospective observation including brain T2-FLAIR magnetic resonace imaging for 32 asymptomatic Stage B (mean age 63.3{+/-}10.5 years; 25% women) and 23 symptomatic Stage C CHF patients (mean age 67.3{+/-}7.1 years; 30% women). Plasma proteomics and Mendelian randomization (MR) were used to identify candidate proteins associated with both CHF and WMH. The association of candidate proteins was further investigated using complementary analyses in CHF rats, cultured cortical neurons, and community-based genetic data in UK Biobank. Results: Global WMH volume increased more in Stage C than Stage B patients, predominantly near the anterior periventricular white matter, despite comparable cardiac indices (4,717{+/-}5,335 mm3 vs. 2,116{+/-}3,134 mm3, P=0.027). SomaScan-based proteomic analysis of plasma samples from this patient cohort revealed that 44 proteins are significantly associated with both Stage C CHF and WMH progression (P<0.05). Of these 44 proteins, two-step Mendelian randomization analysis identified inosine triphosphate pyrophosphatase (ITPA) as the only candidate protein, further supported by an association between rare variants in ITPA and FA. In CHF rats, the anterior pericallosal cortex showed decreases in myelin basic protein density and FA and an increase in ITPA expression compared to sham rats. In cultured cortical neurons, recombinant ITPA exposure reduced total axonal length. Conclusions: Symptomatic CHF was associated with WMH and impaired white matter integrity. ITPA emerged as a candidate factor across human, animal, and cellular analyses. These findings provide a basis for investgating the biological pathways linking CHF and white matter injury.

neuroscience↗

bioRxiv2026

Iron-dependent reprogramming of damage-associated peptide receptor signaling coordinates immunity and phosphate stress adaptation

Plant adaptation to inorganic phosphate (Pi) limitation entails extensive developmental and metabolic reprogramming, collectively termed the phosphate starvation response (PSR). How plants balance nutrient acquisition with immune competence remains unresolved. Here, we show that PSR selectively remodels pattern-recognition receptor (PRR) signaling in Arabidopsis thaliana. Membrane proteomics reveals increased abundance of the Pep receptor PEPR1 under Pi deficiency, whereas most receptor kinases, including the microbial PRRs FLS2 and CERK1, are reduced. Immunoblotting further shows increased PEPR2 abundance. Consistently, Pep-triggered responses are strongly potentiated under Pi depletion, while flagellin- and chitin-induced responses are not, indicating selective PEPR sensitization rather than global immune suppression. This sensitization requires the PSR-associated ferroxidases LPR1/LPR2, NADPH oxidases RBOHD/RBOHF, and transcription factor WRKY33, linking iron-dependent redox remodeling to immune amplification. Beyond inducible defense, PEPRs promote basal PSR transcriptional reprogramming and growth under Pi limitation. Loss of PEPR1/PEPR2 compromises bacterial resistance and alters root-associated microbiota assembly under nutrient deficiency. Together, Pi depletion selectively sensitizes specific PRR pathways. PEPRs exhibit context-dependent dual functionality, promoting either immunity or nutrient stress adaptation, potentially in response to distinct PROPEP-derived ligands, thereby supporting nutrient acquisition without compromising immune vigilance. These findings provide a framework for how nutritional status selectively remodels PRR signaling to coordinate immunity with nutrient stress adaptation.

plant biology↗

bioRxiv2025

Cellular energy sensor SnRK1 suppresses salicylic acid-dependent and -independent defenses and bacterial resistance in Arabidopsis

In nature, plants cope with various pathogens that compete for cellular resources during infection. It has long been suggested that plant defense activity must be linked to cellular energy and metabolic states to optimize the balance between growth and defense. However, the molecular mechanisms that regulate immune activity in relation to cellular energy status remain unclear. Here, we demonstrate that the plant energy sensor SNF1-RELATED KINASE 1 (SnRK1) plays a critical role in modulating defense responses and bacterial resistance in Arabidopsis thaliana. Bacterial elicitor-induced expression of defense marker genes, such as PATHOGENESIS-RELATED 1 (PR1), is significantly repressed under sugar-limited conditions in wild-type seedlings, whereas this expression is markedly enhanced in the snrk1 knockdown mutants. SnRK1 restricts defense-related gene expression and resistance to the biotrophic bacterial pathogen Pseudomonas syringe pv. tomato DC3000, which are partly dependent on salicylic acid (SA). In addition, we found that the SnRK1 kinase activity is increased by high humidity. Consistently, SnRK1 is critical for the suppression of SA-mediated defense responses under high humidity conditions. SnRK1 physically associates with the SA-related transcription factors TGACG SEQUENCE-SPECIFIC BINDING PROTEIN 4 (TGA4) and TGA2 to attenuate PR1 expression. These findings provide valuable insight into the molecular mechanisms linking cellular energy status with immune regulation in plants.

plant biology↗

bioRxiv2025

Ectoine production by newly isolated halophilic methanotroph Methylotuvimicrobium percolatum using surplus methane from anaerobic digestion

Anaerobic digestion (AD) processes that convert waste such as livestock wastewater into biomethane for energy recovery are expanding globally. However, biogas exceeding storage capacity is typically flared, resulting in the release of carbon dioxide, a greenhouse gas. To address this issue, we focused on halophilic methane-oxidizing bacteria (methanotrophs) capable of converting methane into ectoine, a high-value compatible solute widely used in more than 400 cosmetic active ingredients and valued at approximately US$1,000/kg. Nevertheless, research on halophilic methanotrophs and ectoine biosynthesis remains limited. Here, we report the successful isolation of the Type I methanotroph Methylotuvimicrobium percolatum from activated sludge in a brackish water environment. Complete genome sequencing revealed genes for methane oxidation, osmoadaptation, and notably the ectABCask cluster responsible for ectoine biosynthesis. Activity tests under varying NaCl concentrations confirmed ectoine production, with a maximum yield of 20.1 mg ectoine/g-DCW achieved at 25% methane, 30 {degrees}C, and 3 wt% salinity. Biomass growth remained robust up to 6% salinity but declined sharply at higher NaCl concentrations, indicating that optimal conditions for growth and ectoine synthesis do not entirely coincide. These findings advance the fundamental understanding of halophilic methanotroph physiology and highlight their potential as sustainable platforms for converting surplus methane from AD processes into commercially valuable ectoine.

microbiology↗

bioRxiv2025

Development of a digital analysis system for a novel 3D culture-based colony formation to detect malignantly transformed cells in human cell-based therapeutic products

The presence of malignantly transformed cells in human cell-based therapeutic products (hCTPs) is a significant safety concern. Although such cellular impurities in hCTPs can be assessed by detecting anchorage-independent growth using conventional soft agar colony formation (SACF) assays, the sensitivity of these assays is often insufficient. To overcome this limitation, we previously developed a novel tumorigenicity-associated testing method, the digital SACF (D-SACF) assay, which combines a partitioned culture of test cells to concentrate target cells with colony detection via image analysis. However, conventional soft agar culture involves complicated operations, such as preparing multilayered culture media and temperature control, and further technical optimization is required for the widespread adoption of the D-SACF assay. In this study, we focused on a new culture system incorporating a three-dimensional (3D) culture method using a liquid medium containing the low-molecular-weight agar polymer LA717 in low-adhesion culture vessels. We initially confirmed conditions for the efficient high-density 3D culture of normal cells using LA717-supplemented medium in low-adhesion 96-well plates. Using human mesenchymal stem/stromal cells (MSCs) as a normal cell model and HeLa cells as a transformed cell model, we demonstrated that the new 3D culture system effectively maintained the dispersion of MSCs and prevented their aggregation, while transformed HeLa cells exhibited robust anchorage independence, thereby establishing the new liquid/low-molecular-weight agar colony formation (LACF) method as an alternative to SACF. Finally, by systematizing the digital analysis system for the LACF assay (D-LACF assay), which streamlines the overall workflow from the performance evaluation of the test method to product testing and result interpretation, the limitations of the conventional soft agar-based D-SACF assay were addressed and its practicality and utility were enhanced. This in vitro evaluation system is expected to provide a promising approach for improving the quality and safety of hCTPs.

bioengineering↗

bioRxiv2025

Humidity-driven ABA depletion determines plant-pathogen competition for leaf water

Bacterial phytopathogens, such as Pseudomonas syringae pv. tomato (Pst) DC3000, induce water-soaked lesions in the leaf apoplast under high humidity, facilitating infection. However, it remains largely unclear how plants regulate their resistance to restrict bacterial infection in response to humidity. Here, we demonstrate that abscisic acid (ABA)-catabolizing ABA 8-hydroxylase, encoded by CYP707A3, plays a critical role in this resistance in Arabidopsis thaliana. Elevated humidity induces CYP707A3 expression, which is essential for reducing ABA levels and promoting stomatal opening, thereby limiting bacterial water-soaking and infection following leaf invasion. High humidity also increases cytosolic Ca2+ levels via the Ca2+ channels CNGC2 and CNGC4, with partial involvement from CNGC9, activating the calmodulin-binding transcription activator CAMTA3 to drive CYP707A3 induction. However, Pst DC3000 counteracts this defense response using type III secretion effectors, particularly AvrPtoB, facilitating water-soaking. These findings provide insights into the mechanisms underlying the competition between plants and bacteria for leaf water under elevated humidity.

plant biology↗

bioRxiv2024

Meta-omic insights into active bacteria mediating N2O mitigation and dissimilatory nitrate reduction to ammonium in an ammonia recovery bioreactor

Shifting from ammonia removal to recovery is the current strategy in wastewater treatment management. We recently developed a microaerophilic activated sludge (MAS) system for retaining ammonia while removing organic carbon with minimal N2O emissions. A comprehensive understanding of nitrogen metabolisms in the MAS system is essential to optimize system performance. Here, we employed metagenomics and metatranscriptomics analyses to characterize the microbial community structure and activity during the transition from a microaerophilic to an aerobic condition. A hybrid approach of high-quality Illumina short reads and Nanopore long reads recovered medium-to high-quality 98 non-redundant metagenome-assembled genomes (MAGs) from the MAS communities. The suppressed bacterial ammonia monooxygenase (amoA) expression was upregulated after shifting from a microaerophilic to an aerobic condition. The 73 MAGs (>74% of the total) from 11 bacterial phyla harbored genes encoding proteins involved in nitrate respiration; 39 MAGs ([~]53%) carried N2O reductase (nosZ) genes with the predominance of clade II nosZ (31 MAGs), and 24 MAGs ([~]33%) possessed nitrite reductase (ammonia forming) genes (nrfA). Clade II nosZ and nrfA genes exhibited the highest and second-highest expressions among nitrogen metabolism genes, indicating robust N2O consumption and ammonification. Non-denitrifying clade II nosZ bacteria, Cloacibacterium spp., in the most abundant and active phylum Bacteroioda, were likely major N2O sinks. Elevated dissolved oxygen (DO) concentration inhibited clade II nosZ expression but not nrfA expression, potentially switching phenotypes from N2O reduction to ammonification. Collectively, the multi-omics analysis illuminated vital bacteria responsible for N2O reduction and ammonification in microaerophilic and aerobic conditions, facilitating high-performance ammonia recovery.

ecology↗

bioRxiv2023

Potential survival strategies of novel comammox and nitrite-oxidizing Nitrospira present in a reactor treating high-ammonia brackish landfill leachate

Nitrification is mediated by numerous different microorganisms, but knowledge of their ecophysiologies is insufficient. Leachate in the late stages of landfill operation provides a brackish environment with a high ammonia concentration, and methanol is added as an electron donor for denitrification. Such a unique environment may contain novel nitrifiers. Here, we present metagenomic analysis of the microbiome from a closed landfill leachate treatment facility to investigate the identity and functions of nitrifiers. Using a genome-centric approach with metagenomic analysis, we retrieved draft genomes for a novel complete ammonia-oxidizing (comammox) bacterium Nitrospira LAS72; and canonical Nitrospira LAS18, clustered within a novel sub-lineage VII of Nitrospira; Candidatus Nitrosocosmicus LAS21 and Nitrosarchaeum LAS73, belonging to the ammonia-oxidizing archaea (AOA). This is the first evidence of comammox Nitrospira in a high-ammonia-containing brackish environment. Canonical ammonia-oxidizing bacteria were not detected. Given the brackish environment and supplementation of methanol used in the facility, we also investigated the methanol metabolism of these nitrifiers and their potential to produce compatible solutes as osmoprotectants. Uniquely among Nitrospira, comammox Nitrospira LAS72 possesses genes associated with formaldehyde reductase and glycine betaine biosynthesis. Thus, Nitrospira LAS72 may proliferate because of the availability of formaldehyde upstream of carbon metabolism and adapt to fluctuating osmotic pressure by producing a variety of compatible solutes. The discovery of this novel comammox Nitrospira, and canonical Nitrospira forming a new sub-lineage VII in an ammonia-concentrated brackish environment broadens our knowledge of the diversity and functions of nitrifying microorganisms.

microbiology↗

bioRxiv2023

CTRP7 as a Molecular Biomarker for Predicting Responsiveness to Pulmonary Vasodilators: Insights from Human and Animal Studies in Pulmonary Arterial Hypertension

BackgroundPulmonary arterial hypertension (PAH) is a life-threatening condition. Although pulmonary vasodilators have shown promise in managing PAH, the overall prognosis improvement is modest, partly because of the absence of a biomarker for guiding their selection. This study aimed to identify the molecular-based predictors of responsiveness to pulmonary vasodilators by combining human and basic studies. Methods and ResultsRNA sequencing was conducted on cultured pulmonary artery smooth muscle cells (PASMCs) from patients with and without PAH, identifying variations in 2,076 genes. The candidates were narrowed down to established clinical biomarkers, and their plasma levels were assessed in PAH (n = 123) and non-PAH patients (n = 25). C1q/TNF-related protein 7 (CTRP7) exhibited elevated expression in PASMCs (5.37 Log2 fold change, p < 0.01), and the plasma of patients with PAH compared to non-PAH (28.2 (9.3- 101.2) vs. 9.32 (4.6-18.6) ng/ml, p < 0.01). A plasma assessment revealed a significant correlation between CTRP7 and interleukin 6 (IL-6) levels (r = 0.544, p < 0.001). Chromatin immunoprecipitation demonstrated that IL-6 upregulated CTRP7 expression in PASMCs. Among pivotal factors, CTRP7 reduced prostacyclin analog receptor (PTGIR) expression through Rab5a-mediated internalization, resulting in diminished responsiveness to selexipag (a prostacyclin analog). Incorporating the human study, hypoxic PH mice demonstrated reduced PTGIR expression in the pulmonary arteries, which correlated with limited responses to selexipag treatment (low cardiac output and persistent pulmonary artery resistance), which was mitigated by silencing CTRP7 expression in the pulmonary arteries using adeno-associated virus 6. ConclusionsAmong the candidates with increased expression in patients with PAH based on RNA sequencing of PASMCs, CTRP7 demonstrated elevated plasma levels compared to non-PAH. CTRP7 regulated PTGIR internalization via inflammation and Rab5a, influencing responsiveness to selexipag. CTRP7 emerged as a compelling biomarker for predicting responsiveness to prostacyclin analogs, potentially advancing the development of innovative PAH treatment strategies. Novel and SignificanceO_ST_ABSWhat Is Known?C_ST_ABSO_LIPulmonary arterial hypertension (PAH) is a life-threatening vascular disease with limited treatment options. C_LIO_LIAlthough pulmonary vasodilators have shown promise in managing PAH, the overall improvement in prognosis is modest. C_LIO_LIFurther research is needed to understand the molecular features of pulmonary vasodilators and identify biomarkers for appropriate selection. C_LI What New Information Does This Article Contribute?O_LIC1q/TNF-related protein 7 (CTRP7) was found to be elevated in the pulmonary artery smooth muscle cells (PASMCs) and plasma of patients with pulmonary arterial hypertension (PAH). C_LIO_LIThis study established a connection between inflammation and pulmonary vascular responsiveness via CTRP7-mediated internalization and degradation of the prostacyclin analog receptor. C_LIO_LIThis study indicated the possibility of using plasma CTRP levels as a clinical biomarker to monitor pulmonary responsiveness, which can contribute to the development of novel treatment strategies for patients with PAH. C_LI Pulmonary arterial hypertension (PAH) is a life-threatening and enigmatic lung vascular disorder characterized by progressive pulmonary vascular remodeling and vasoconstriction. Despite significant advancements in the treatment of PAH using pulmonary vasodilators, some individuals display limited responses, primarily due to a lack of understanding of the molecular features of each pulmonary vasodilator and the absence of a biomarker for appropriate selection. The present study aimed to identify promising biomarkers for predicting a patients responsiveness to pulmonary vasodilators through a two-step approach, involving RNA sequencing of PASMCs and the measurement of plasma levels. CTRP7 emerged as a prominent biomarker, displaying increased expression in both PASMCs and plasma obtained from patients with PAH. Mechanistically, IL-6 transcriptionally modulated CTPR7, leading to the internalization and degradation of PTGIR, resulting in a reduced response to selexipag (prostacyclin analog) in PASMCs. Integrating the human studies, a hypoxic mouse model exhibited lower PTGIR expression in pulmonary arteries, correlating with limited responses to selexipag treatment, which were ameliorated by silencing CTRP7 expression in pulmonary arteries using adeno-associated virus 6 transduction. This study collectively demonstrates that CTRP7 emerges as a compelling biomarker for predicting responsiveness to prostacyclin analogs, with the potential to advance the development of innovative PAH treatment strategies.

molecular biology↗

bioRxiv2023

Temporal segmentation and 'look ahead' simulation: Physical events structure visual perception of intuitive physics

How we perceive the physical world is not only organized in terms of objects, but also structured in time as sequences of events. This is especially evident in intuitive physics, with temporally bounded dynamics such as falling, occlusion, and bouncing demarcating the continuous flow of sensory inputs. While the spatial structure and attentional consequences of physical objects have been well-studied, much less is known about the temporal structure and attentional consequences of physical events in visual perception. Previous work has recognized physical events as units in the mind, and used pre-segmented object interactions to explore physical representations. However, these studies did not address whether and how perception imposes the kind of temporal structure that carves these physical events to begin with, and the attentional consequences of such segmentation during intuitive physics. Here, we use performance-based tasks to address this gap. In Experiment 1, we find that perception not only spontaneously separates visual input in time into physical events, but also, this segmentation occurs in a nonlinear manner within a few hundred milliseconds at the moment of the event boundary. In Experiment 2, we find that event representations, once formed, use coarse look ahead simulations to selectively prioritize those objects that are predictively part of the unfolding dynamics. This rich temporal and predictive structure of physical events, formed during vision, should inform models of intuitive physics.

neuroscience↗

bioRxiv2022

CiDRE+ M2c macrophages hijacked by SARS-CoV-2 cause COVID-19 severity

Infection of the lungs with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via the angiotensin I converting enzyme 2 (ACE2) receptor induces a type of systemic inflammation known as a cytokine storm. However, the precise mechanisms involved in severe coronavirus disease 2019 (COVID-19) pneumonia are unknown. Here, we show that interleukin-10 (IL-10) changed normal alveolar macrophages into ACE2-expressing M2c-type macrophages that functioned as spreading vectors for SARS-CoV-2 infection. The depletion of alveolar macrophages and blockade of IL-10 attenuated SARS-CoV-2 pathogenicity. Furthermore, genome-wide association and quantitative trait locus analyses identified novel mRNA transcripts in human patients, COVID-19 infectivity enhancing dual receptor (CiDRE), which has unique synergistic effects within the IL-10-ACE2 system in M2c-type macrophages. Our results demonstrate that alveolar macrophages stimulated by IL-10 are key players in severe COVID-19. Collectively, CiDRE expression levels are potential risk factors that predict COVID-19 severity, and CiDRE inhibitors might be useful as COVID-19 therapies. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=195 HEIGHT=200 SRC="FIGDIR/small/510331v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@1e96c82org.highwire.dtl.DTLVardef@1d2dc32org.highwire.dtl.DTLVardef@7689d1org.highwire.dtl.DTLVardef@520d17_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2022

Microaerophilic activated sludge system for ammonia recovery from high-strength nitrogenous wastewater: Performance and microbial communities

A transition to ammonia recovery from wastewater has started; however, a technology for sustainable nitrogen retention in the form of ammonia is still in development. This study validated a microaerophilic activated sludge (MAS) system to efficiently retain ammonia from high-strength nitrogenous wastewater. The MAS is based on conventional activated sludge (CAS) with aerobic and settling compartments. Low dissolved oxygen (DO) concentrations (<0.1 mg/L) and short solid retention times (SRTs) (<5 d) eliminated nitrifying bacteria. The two parallel MASs were successfully operated for 300 d and had ammonia retention of 101.7 {+/-} 24.9% and organic carbon removal of 85.5 {+/-} 8.9%. The MASs mitigated N2O emissions with an emission factor of <0.23%, much lower than the default value of CAS (1.6%). A short-term step-change test demonstrated that N2O indicated the initiation of nitrification and the completion of denitrification in the MAS. The parallel MASs had comparable microbial diversity, promoting organic carbon oxidation while inhibiting ammonia-oxidizing microorganisms (AOMs), as revealed by 16S rRNA gene amplicon sequencing, qPCR of functional genes, and fluorescent in situ hybridization of {beta}-Proteobacteria AOB. The microbial analyses also uncovered that filamentous bacteria were positively correlated with effluent turbidity. Together, controlling DO and SRT achieved successful ammonia retention, mainly by suppressing AOM activity. This process represents a new nitrogen management paradigm. SynopsisMoving from nitrogen removal to nitrogen recovery is critical for establishing a sustainable society. We provided proof-of-the-concept for a novel ammonia retention technology by retrofitting an activated sludge system.

microbiology↗

bioRxiv2020

TGN/EE SNARE protein SYP61 is ubiquitinated and required for carbon/nitrogen-nutrient responses in Arabidopsis

Ubiquitination is a post-translational modification with reversible attachment of the small protein ubiquitin, which is involved in numerous cellular processes including membrane trafficking. For example, ubiquitination of cargo proteins is known to regulate their subcellular dynamics, and plays important roles in plant growth and stress adaptation. However, the regulatory mechanism of the trafficking machinery components remains elusive. Here, we report Arabidopsis trans-Golgi network/early endosome (TGN/EE) localized soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) protein SYP61 as a novel ubiquitination target of a membrane localized ubiquitin ligase ATL31. SYP61 is a key component of membrane trafficking in Arabidopsis. SYP61 was ubiquitinated with K63-linked chain by ATL31 in vitro and in plants. The knockdown mutants of SYP61 were hypersensitive to the disrupted carbon (C)/nitrogen (N)-nutrient stress, suggesting its critical role in plant homeostasis in response to nutrients. We also found the ubiquitination status of SYP61 is affected by C/N-nutrient availability. These results provided possibility that ubiquitination of SNARE protein has important role in plant physiology.

plant biology↗

bioRxiv2020

Intravenous edaravone plus therapeutic hypothermia offers limited neuroprotection in the hypoxic-ischaemic newborn piglet

Therapeutic hypothermia is a standard therapy for neonatal hypoxic-ischaemic encephalopathy. One potential additional therapy is the free radical scavenger edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one). To compare the neuroprotective effects of edaravone plus therapeutic hypothermia with those of therapeutic hypothermia alone after a hypoxic-ischaemic insult in the newborn piglet, anaesthetized piglets were subjected to 40 min of hypoxia (3-5% inspired oxygen) and cerebral ischaemia was assessed by cerebral blood volume. Body temperature was maintained at 38.5 {degrees}C in the normothermia group (NT, n = 8) and at 34 {degrees}C (24 h after the insult) in the therapeutic hypothermia (TH, n = 7) and therapeutic hypothermia plus edaravone (3 mg intravenous every 12 h for 3 days after the insult; TH+EV, n = 6) groups under mechanical ventilation. Five days after the insult, the mean (standard deviation) neurological scores were 10.9 (5.7) in the NT group, 17.0 (0.4) in the TH group (p = 0.025 vs. NT) and 15.0 (3.9) in the TH+EV group. The histopathological score of the TH+EV group showed no significant improvement compared with that of the other groups. In conclusion, edaravone plus therapeutic hypothermia had no additive neuroprotective effects after hypoxia-ischaemia in neurological and histopathological assessments.

neuroscience↗