Approach Model Research Articles

Invasion of spontaneous germinal centers by naive B cells is rapid and persistent.

In autoreactive germinal centers (GC) initiated by a single rogue B cell clone, wild-type B cells expand and give rise to clones that target other autoantigens, known as epitope spreading. The chronic, progressive nature of epitope spreading calls for early interventions to limit autoimmune pathologies, but the kinetics and molecular requirements for wild-type B cell invasion and participation in GC remain largely unknown. With parabiosis and adoptive transfer approaches in a murine model of systemic lupus erythematosus, we demonstrate that wild-type B cells join existing GCs rapidly, clonally expand, persist, and contribute to autoantibody production and diversification. The invasion of autoreactive GCs by wild-type B cells required TLR7, B cell receptor specificity, antigen presentation, and type I interferon signaling. The adoptive transfer model provides a tool for identifying early events in the breaking of B cell tolerance in autoimmunity.

Abstract 4206: Regional transcriptomic profiling of the head and neck squamous cell carcinoma tumor microenvironment paired with murine models identify extracellular matrix components that mediate tumor progression and immune suppression

Abstract Purpose: A substantial contribution to the poor prognosis for head and neck squamous cell carcinoma (HNSCC) patients is the progression to distant metastasis. This occurs in 30% of patients over the course of their disease, and radically reduces the 5-year survival rate to under 50%. Investigations in recent years have begun to unveil the intricate interplay of the extracellular matrix (ECM) in both tumor-intrinsic signaling and immunoregulation. However, studies conducted in the context of metastatic have been limited. Here, we employ spatial transcriptomics on HNSCC patient biopsies to identify ECM components that may contribute to cancer progression and immune suppression. Experimental design: Comprehensive transcriptome profiling of HNSCC patient biopsies was conducted using the GeoMx Digital Spatial Profiler (DSP). This approach allowed us to characterize regions of the tumor microenvironment (TME) by immunofluorescent staining for subsequent bioinformatic analysis. To investigate the biological consequences of associations observed in our dataset, we performed in vivo murine studies. We have produced a series of SCC C57BL/6 murine cell lines derived from Smad4-/-KrasG12D Keratin15+ stem cells, which faithfully mimic the clinical progression of HNSCC tumors, including metastasis. Using these murine models, we applied relevant pharmacologic inhibitors and genetic knockdown of targets identified with our GeoMx DSP analysis. In vitro immune-based and functional assays were conducted to elucidate the underlying mechanisms contributing to SCC progression. Results: GeoMx DSP analysis revealed that laminins were enriched in stage IV HNSCC patient stroma, relative to lower stage patients. This coincided with TGFβ enrichment and inversely associated with signatures of anti-tumor immune infiltration. Analysis of The Cancer Genome Atlas data revealed similar inverse correlations in SCCs, distinct from breast cancer and lung adenocarcinoma. Our metastatic SCC murine lines likewise exhibited elevated levels of these laminin proteins, accompanied by high levels of laminin-binding integrins and TGFβ-Smad signaling. Independent of impacting cell proliferation, shRNA knockdown of laminin decreased tumor volume in an immune-competent setting. Targeting laminin-integrin signaling with the small molecule inhibitors Galunisertnib and Buparlisib also reduced the metastatic capacity of these cells in C57BL/6 mice. Conclusions: Spatial transcriptomic profiling of the HNSCC TME uncovers intricate associations and promising targets not readily discernible in bulk RNAseq analyses. Validation through genetic and pharmacological approaches in immune-competent models underscores their potential as strategies to reduce HNSCC burden. Citation Format: John D. Aleman, Khoa A. Nguyen, Erica Wong, Yao Ke, Hanne T. Lind, Clifford G. Tepper, Andrew C. Birkeland, Christian D. Young, Sana D. Karam, Xiao-Jing Wang. Regional transcriptomic profiling of the head and neck squamous cell carcinoma tumor microenvironment paired with murine models identify extracellular matrix components that mediate tumor progression and immune suppression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4206.

Application of Machine Learning Approaches in Particle Tracking Model to Estimate Sediment Transport in Natural Streams

Application of Machine Learning Approaches in Particle Tracking Model to Estimate Sediment Transport in Natural Streams

AU Introspection and Symmetry under non-trivial unawareness

This note discusses the relationship between AU Introspection (i.e., an agent is unaware of some event, then she is unaware of that she is unaware of the event) and Symmetry (i.e., an agent is unaware of some event if and only if she is unaware of the complement set) for non-trivial unawareness (i.e., there is an event an agent is unaware of). without Negative Introspection using a set-theoretical approach in standard state-space models. Previous studies have explored the equivalence between Negative Introspection and AU Introspection, or the equivalence between Negative Introspection and Symmetry, by assuming Necessitation of the knowledge operator. As a corollary, AU Introspection is equivalent to Symmetry. However, no studies have shown the relationship between AU Introspection and Symmetry without Necessitation. Therefore, we explore this issue. Our main result shows that if the knowledge operator satisfies Monotonicity, Truth, and Positive introspection, then Modica and Rustichini’s definition of unawareness leads to the equivalence of AU Introspection and Symmetry. In other words, we show that both AU Introspection and Symmetry hold without clashing with non-trivial unawareness.

Plant responses to elevated CO2 under competing hypotheses of nitrogen and phosphorus limitations.

The future ecosystem carbon cycle has important implications for biosphere-climate feedback. The magnitude of future plant growth and carbon accumulation depends on plant strategies for nutrient uptake under the stresses of nitrogen (N) versus phosphorus (P) limitations. Two archetypal theories have been widely acknowledged in the literature to represent N and P limitations on ecosystem processes: Liebig's Law of the Minimum (LLM) and the Multiple Element Limitation (MEL) approach. LLM states that the more limiting nutrient controls plant growth, and commonly leads to predictions of dramatically dampened ecosystem carbon accumulation over the 21st century. Conversely, the MEL approach recognizes that plants possess multiple pathways to coordinate N and P availability and invest resources to alleviate N or P limitation. We implemented these two contrasting approaches in the E3SM model, and compiled 98 in situ forest N or P fertilization experiments to evaluate how terrestrial ecosystems will respond to N and P limitations. We find that MEL better captured the observed plant responses to nutrient perturbations globally, compared with LLM. Furthermore, LLM and MEL diverged dramatically in responses to elevated CO2 concentrations, leading to a two-fold difference in CO2 fertilization effects on Net Primary Productivity by the end of the 21st century. The larger CO2 fertilization effects indicated by MEL mainly resulted from plant mediation on N and P resource supplies through N2 fixation and phosphatase activities. This analysis provides quantitative evidence of how different N and P limitation strategies can diversely affect future carbon and nutrient dynamics.

A modified Mediterranean-style diet enhances brain function via specific gut-microbiome-brain mechanisms.

Alzheimer's disease (AD) is a debilitating brain disorder with rapidly mounting prevalence worldwide, yet no proven AD cure has been discovered. Using a multi-omics approach in a transgenic AD mouse model, the current study demonstrated the efficacy of a modified Mediterranean-ketogenic diet (MkD) on AD-related neurocognitive pathophysiology and underlying mechanisms related to the gut-microbiome-brain axis. The findings revealed that MkD induces profound shifts in the gut microbiome community and microbial metabolites. Most notably, MkD promoted growth of the Lactobacillus population, resulting in increased bacteria-derived lactate production. We discovered elevated levels of microbiome- and diet-derived metabolites in the serum as well, signaling their influence on the brain. Importantly, these changes in serum metabolites upregulated specific receptors that have neuroprotective effects and induced alternations in neuroinflammatory-associated pathway profiles in hippocampus. Additionally, these metabolites displayed strong favorable co-regulation relationship with gut-brain integrity and inflammatory markers, as well as neurobehavioral outcomes. The findings underscore the ameliorative effects of MkD on AD-related neurological function and the underlying gut-brain communication via modulation of the gut microbiome-metabolome arrays.

Evaluation of Leaf‐To‐Canopy Upscaling Approaches for Simulating Canopy Carbonyl Sulfide Uptake and Gross Primary Productivity

AbstractCarbonyl sulfide (COS) measurements provide an important mechanism for quantifying the terrestrial carbon and water cycles. Terrestrial photosynthesis can be inferred from vegetative uptake of COS due to the shared diffusion pathway of COS and CO2 into the chloroplasts. However, the efficacy of different leaf‐to‐canopy upscaling approaches for estimating plant COS uptake and photosynthesis at the canopy scale remains uncertain. In this study, the daytime canopy COS uptake rate (Fcosc) and gross primary productivity (GPP) were simulated using big leaf (BL), two big leaf (TBL) and two leaf (TL) upscaling approaches in the Boreal Ecosystem Productivity Simulator terrestrial biosphere model for two forest sites. We found that TL and TBL performed better than BL in estimating GPP as evaluated by the eddy covariance derived GPP at the studied sites. BL overestimated GPP and canopy stomatal conductance to COS (Gs_cos), resulting from the overestimation of canopy intercepted solar radiation. The positive biases of GPP by TBL could be attributed to the positive biases in GPP of shaded leaves by TBL. The results in this study demonstrate the improved accuracy in using TL for estimating GPP at the canopy scale. Improved leaf‐to‐canopy upscaling approach in terrestrial biosphere models will improve the accuracy of canopy COS uptake and GPP estimation on regional to global scales.

Applying Proteomics and Computational Approaches to Identify Novel Targets in Blast-Associated Post-Traumatic Epilepsy.

Traumatic brain injury (TBI) can lead to post-traumatic epilepsy (PTE). Blast TBI (bTBI) found in Veterans presents with several complications, including cognitive and behavioral disturbances and PTE; however, the underlying mechanisms that drive the long-term sequelae are not well understood. Using an unbiased proteomics approach in a mouse model of repeated bTBI (rbTBI), this study addresses this gap in the knowledge. After rbTBI, mice were monitored using continuous, uninterrupted video-EEG for up to four months. Following this period, we collected cortex and hippocampus tissues from three groups of mice: those with post-traumatic epilepsy (PTE+), those without epilepsy (PTE-), and the control group (sham). Hundreds of differentially expressed proteins were identified in the cortex and hippocampus of PTE+ and PTE- relative to sham. Focusing on protein pathways unique to PTE+, pathways related to mitochondrial function, post-translational modifications, and transport were disrupted. Computational metabolic modeling using dysregulated protein expression predicted mitochondrial proton pump dysregulation, suggesting electron transport chain dysregulation in the epileptic tissue relative to PTE-. Finally, data mining enabled the identification of several novel and previously validated TBI and epilepsy biomarkers in our data set, many of which were found to already be targeted by drugs in various phases of clinical testing. These findings highlight novel proteins and protein pathways that may drive the chronic PTE sequelae following rbTBI.

Incidence and Antepartum Risk Factors of Severe Postpartum Haemorrhage in Anaemic Pregnant Women in Lagos, Nigeria: A Secondary Cohort Analysis.

The magnitude and risk factors for postpartum haemorrhage (PPH) have been extensively investigated, although little is currently known about the incidence and predictors of severe PPH, specifically among women affected by prenatal anaemia in Nigeria. The study determined the incidence and antepartum risk factors of severe PPH in anaemic pregnant women in five health institutions in Lagos, Southwest Nigeria. A secondary analysis was performed using the data of pregnant women with anaemia from the "Predict-PPH" study that was conducted between January and June 2023. This study included n=570 pregnant women affected by anaemia who gave birth in five hospitals in the Lagos metropolis of Nigeria. The study outcome was severe PPH, defined as an estimated blood loss of at least 1000 mL within 24 hours of childbirth. A backward stepwise conditional approach in a multivariable logistic regression model was utilised to identify the independent risk factors for severe PPH in anaemic pregnant women. Of the 570 women with prenatal anaemia enrolled in the primary study, 42 (7.4%) had severe PPH. The identified independent risk factors for severe PPH were maternal obesity (adjusted OR = 3.85, 95% CI = 1.85-8.02), antepartum haemorrhage in index pregnancy (adjusted OR = 2.98, 95% CI = 1.29-6.90), uterine fibroids (adjusted OR = 6.10, 95% CI = 2.39-15.52), delivery gestational age ≥39 weeks (adjusted OR = 2.62, 95% CI = 1.23-5.56), and delivery by caesarean birth (adjusted OR = 16.75, 95% CI = 5.81-48.31). About one in 13 anaemic pregnant women enrolled in the study developed severe PPH during childbirth. Maternal obesity, antepartum bleeding in the current pregnancy, co-existing uterine fibroids in pregnancy, delivery gestational age beyond 38 weeks, and caesarean birth in the current pregnancy were factors that were significantly associated with severe PPH in anaemic pregnant women. These findings underscore the importance of increased vigilance during both the antenatal and peripartum periods to identify women with these risk factors for the initiation of timely interventions to prevent severe PPH.

Radiofrequency Combined with Intratumoral Immunotherapy: Preclinical Results and Safety in Metastatic Colorectal Carcinoma.

Radiofrequency ablation (RFA) of cancer induces an anti-tumor immunity, which is insufficient to prevent recurrences. In mice, RFA-intratumoral immunotherapy by granulocyte-macrophage colony-stimulating factor (GM-CSF) and Bacillus Calmette-Guerin resulted in complete metastases regression. Infectious risk in human needs replacement of live vaccines. Intratumoral purified protein derivatives (PPD) have never been tested in digestive cancers, and the safety of intratumoral immunotherapy after RFA has not yet been validated in human models. We investigated the therapeutic efficacy of combined radiofrequency ablation (RFA) and intratumoral immunotherapy (ITI) using an immune-muco-adherent thermogel (IMT) in a mouse model of metastatic colorectal cancer (CRC) and the safety of this approach in a pig model. Intratumoral stability of the immunogel was assessed using magnetic resonance imaging (MRI) and bioluminescent imaging. Seventy-four CT26 tumor-bearing female BALB/c mice were treated with RFA either alone or in combination with intratumoral IMT. Regression of distant metastasis and survival were monitored for 60 days. Six pigs that received liver radiofrequency and intralesional IMT injections were followed for 15 days. Experimental gel embolisms were treated using an intravascular approach. Pertinent rheology of IMT was confirmed in tumors, by the signal stability during 3 days in MRI and 7 days in bioluminescence imaging. In mice, the abscopal effect of RFA-intratumoral immunotherapy resulted in regression of distant lesions completed at day 16 vs. a volume of 350 ± 99.3 mm3 in the RFA group at day 25 and a 10-fold survival rate at 60 days. In pigs, injection of immunogel in the liver RFA area was safe after volume adjustment without clinical, hematological, and liver biology disorder. Flow cytometry showed an early increase in CD3 TCRγδ+T cells at D7 (p < 0.05) and a late decrease in CD29+-CD8 T cells at D15 (p < 0.05), reflecting the inflammation status changes. Systemic GM-CSF release was not detectable. Experimental caval and pulmonary thermogel embolisms were treated by percutaneous catheterism and cold serum infusion. RFA-intratumoral immunotherapy as efficient and safe mini-invasive interventional oncology is able to improve ablative treatment of colorectal liver metastases.

Sistem Informasi Buku Tamu Berbasis Website pada Kantor Badan Pertanahan Nasional Kota Medan

The web-based guest book information system is an innovative solution designed for easy and efficient management of guest books at the National Land Agency office in Medan City. Using the PhpMyAdmin database system, an open-source web-based program built to simplify guest book management. The focus of this research is on the web-based guest book information system, which makes it easy for employees to record and monitor guest data at specific times. This research uses the Waterfall Method, a software built using a methodical and sequential approach in the classic model. The results of this study show that the web-based guest book information system is an effective solution for managing data and monitoring guest visits at the National Land Agency office in Medan City. Using web technology, guest information can be accessed quickly and accurately.

Gene editing improves endoplasmic reticulum-mitochondrial contacts and unfolded protein response in Friedreich's ataxia iPSC-derived neurons.

Friedreich ataxia (FRDA) is a multisystemic, autosomal recessive disorder caused by homozygous GAA expansion mutation in the first intron of frataxin (FXN) gene. FXN is a mitochondrial protein critical for iron-sulfur cluster biosynthesis and deficiency impairs mitochondrial electron transport chain functions and iron homeostasis within the organelle. Currently, there is no effective treatment for FRDA. We have previously demonstrated that single infusion of wild-type hematopoietic stem and progenitor cells (HSPCs) resulted in prevention of neurologic and cardiac complications of FRDA in YG8R mice, and rescue was mediated by FXN transfer from tissue engrafted, HSPC-derived microglia/macrophages to diseased neurons/myocytes. For a future clinical translation, we developed an autologous stem cell transplantation approach using CRISPR/Cas9 for the excision of the GAA repeats in FRDA patients' CD34+ HSPCs; this strategy leading to increased FXN expression and improved mitochondrial functions. The aim of the current study is to validate the efficiency and safety of our gene editing approach in a disease-relevant model. We generated a cohort of FRDA patient-derived iPSCs and isogenic lines that were gene edited with our CRISPR/Cas9 approach. iPSC derived FRDA neurons displayed characteristic apoptotic and mitochondrial phenotype of the disease, such as non-homogenous microtubule staining in neurites, increased caspase-3 expression, mitochondrial superoxide levels, mitochondrial fragmentation, and partial degradation of the cristae compared to healthy controls. These defects were fully prevented in the gene edited neurons. RNASeq analysis of FRDA and gene edited neurons demonstrated striking improvement in gene clusters associated with endoplasmic reticulum (ER) stress in the isogenic lines. Gene edited neurons demonstrated improved ER-calcium release, normalization of ER stress response gene, XBP-1, and significantly increased ER-mitochondrial contacts that are critical for functional homeostasis of both organelles, as compared to FRDA neurons. Ultrastructural analysis for these contact sites displayed severe ER structural damage in FRDA neurons, that was undetected in gene edited neurons. Taken together, these results represent a novel finding for disease pathogenesis showing dramatic ER structural damage in FRDA, validate the efficacy profile of our FXN gene editing approach in a disease relevant model, and support our approach as an effective strategy for therapeutic intervention for Friedreich's ataxia.

Systematic review of hematopoietic stem cell gene therapy approach in thalassemia: Comparative analysis in animal models.

Hematopoietic stem cell (HSC) gene therapy has shown potential as a therapeutic approach for thalassemia in recent years. However, a comparison of the varying gene therapy methods of HSC gene therapy in thalassemia has never been reviewed. This study aims to evaluate the utilization of HSC gene therapy approaches in animal models of thalassemia. A systematic review was conducted in five databases: PubMed, EBSCOHost, Science Direct, SCOPUS, and Proquest using a combination of the terms hematopoietic stem cell or hematopoietic stem cell or HSC, thalassemia, genetic therapy or gene therapy and animal model. Only journals published in English between 2008 and 2023 were included. This literature included six studies analyzing the use of HSC gene therapy in thalassemic mice models. The three outcomes being assessed in this review were globin levels, hematological parameters, and red blood cell (RBC) phenotypes. Gene therapy approaches for thalassemia using HSC showed significant improvement in β-globin levels and RBC phenotypes. Phenotypic improvements were also observed. These outcomes indicate good efficacy in gene therapy for thalassemia in mice models. Furthermore, more studies assessing the efficacy of HSC gene therapy in the human model should be done in future studies.

7,8‑Dihydroxyflavone functions as an antioxidant through the inhibition of Kelch‑like ECH‑associated protein 1: Molecular docking and an in vivo approach in a rat model of ischemia‑reperfusion brain injury

7,8‑Dihydroxyflavone functions as an antioxidant through the inhibition of Kelch‑like ECH‑associated protein 1: Molecular docking and an <i>in vivo</i> approach in a rat model of ischemia‑reperfusion brain injury

Investigating and Advancing Approaches in Deep Learning Models: Platforms, Applications, and the Dynamics of Emerging Research Trends

Investigating and Advancing Approaches in Deep Learning Models: Platforms, Applications, and the Dynamics of Emerging Research Trends

Strong Extratropical Impact on Observed ENSO

Abstract Previous studies have indicated that the extratropics can influence ENSO via specific processes. However, it is still unclear to what extent ENSO is influenced by the extratropics in observation. Now we assess this issue by applying the regional data assimilation (RDA) approach in an advanced model, the GFDL CM2.1. Our study confirms a strong extratropical impact on observed ENSO. Quantitatively, the extratropical atmospheric variability poleward of 20° explains 56% of the observed variance of ENSO and greatly influences ∼67% of observed El Niño events during 1969–2008. This extratropical impact is still significant even as far as poleward of 30°. Furthermore, the impact from the southern extratropics is slightly stronger than that from the northern extratropics, partly caused by the Pacific ITCZ location north of the equator and different mixed-layer depth along the northern Pacific meridional mode (NPMM) and the southern Pacific meridional mode (SPMM). Our study further shows that all of three super El Niño events, those in 1972/73, 1982/83, and 1997/98, are influenced greatly by both hemispheric extratropics, with NPMM and SPMM interfering constructively, while most weak and moderate El Niño events are triggered by only one hemispheric extratropics, with NPMM and SPMM interfering destructively. Besides the extratropical Pacific influence on ENSO via NPMM/SPMM, the extratropics also has a potential impact on ENSO by influencing other tropical oceans and then by interbasin interactions.

Expanding the Genetic Code of Xenopus laevis Embryos.

The incorporation of unnatural amino acids into proteins through genetic code expansion has been successfully adapted to African claw-toed frog embryos. Six unique unnatural amino acids are incorporated site-specifically into proteins and demonstrate robust and reliable protein expression. Of these amino acids, several are caged analogues that can be used to establish conditional control over enzymatic activity. Using light or small molecule triggers, we exhibit activation and tunability of protein functions in live embryos. This approach was then applied to optical control over the activity of a RASopathy mutant of NRAS, taking advantage of generating explant cultures from Xenopus. Taken together, genetic code expansion is a robust approach in the Xenopus model to incorporate novel chemical functionalities into proteins of interest to study their function and role in a complex biological setting.

Barrel cortex development lacks a key stage of hyperconnectivity from deep to superficial layers in a rat model of Absence Epilepsy

During development of the sensory cortex, the ascending innervation from deep to upper layers provides a temporary scaffold for the construction of other circuits that remain at adulthood. Whether an alteration in this sequence leads to brain dysfunction in neuro-developmental diseases remains unknown. Using functional approaches in a genetic model of Absence Epilepsy (GAERS), we investigated in barrel cortex, the site of seizure initiation, the maturation of excitatory and inhibitory innervations onto layer 2/3 pyramidal neurons and cell organization into neuronal assemblies. We found that cortical development in GAERS lacks the early surge of connections originating from deep layers observed at the end of the second postnatal week in normal rats and the concomitant structuring into multiple assemblies. Later on, at seizure onset (1 month old), excitatory neurons are hyper-excitable in GAERS when compared to Wistar rats. These findings suggest that early defects in the development of connectivity could promote this typical epileptic feature and/or its comorbidities.

IFNγ drives neuroinflammation, demyelination, and neurodegeneration in a mouse model of multiple system atrophy

Multiple system atrophy (MSA) is a rare and fatal synucleinopathy characterized by insoluble alpha-synuclein (α-syn) cytoplasmic inclusions located within oligodendroglia. Neuroinflammation, demyelination, and neurodegeneration are correlated with areas of glia cytoplasmic inclusions (GCI) pathology, however it is not known what specifically drives disease pathogenesis. Recent studies have shown that disease pathologies found in post-mortem tissue from MSA patients can be modeled in rodents via a modified AAV overexpressing α-syn, Olig001-SYN, which has a 95% tropism for oligodendrocytes. In the Olig001-SYN mouse model, CD4+ T cells have been shown to drive neuroinflammation and demyelination, however the mechanism by which this occurs remains unclear. In this study we use genetic and pharmacological approaches in the Olig001-SYN model of MSA to show that the pro-inflammatory cytokine interferon gamma (IFNγ) drives neuroinflammation, demyelination, and neurodegeneration. Furthermore, using an IFNγ reporter mouse, we found that infiltrating CD4+ T cells were the primary producers of IFNγ in response to α-syn overexpression in oligodendrocytes. Results from these studies indicate that IFNγ expression from CD4+ T cells drives α-syn-mediated neuroinflammation, demyelination, and neurodegeneration. These results indicate that targeting IFNγ expression may be a potential disease modifying therapeutic strategy for MSA.

The role of serum/glucocorticoid-regulated kinase 1 in brain function following cerebral ischemia

Cardiopulmonary arrest (CA) is a major cause of death/disability in the U.S. with poor prognosis and survival rates. Current therapeutic challenges are physiologically complex because they involve hypoperfusion (decreased cerebral blood flow), neuroinflammation, and mitochondrial dysfunction. We previously discovered novel serum/glucocorticoid-regulated kinase 1 (SGK1) is highly expressed in brain of neurons that are susceptible to ischemia (hippocampus and cortex). We inhibited SGK1 and utilized pharmacological (specific inhibitor, GSK650394) and neuron-specific genetic approaches (shRNA) in rodent models of CA to determine if SGK1 is responsible for hypoperfusion, neuroinflammation, mitochondrial dysfunctional, and neurological deficits after CA. Inhibition of SGK1 alleviated cortical hypoperfusion and neuroinflammation (via Iba1, GFAP, and cytokine array). Treatment with GSK650394 enhanced mitochondrial function (via Seahorse respirometry) in the hippocampus 3 and 7 days after CA. Neuronal injury (via MAP2, dMBP, and Golgi staining) in the hippocampus and cortex was observed 7 days after CA but ameliorated with SGK1-shRNA. Moreover, SGK1 mediated neuronal injury by regulating the Ndrg1-SOX10 axis. Finally, animals subjected to CA exhibited learning/memory, motor, and anxiety deficits after CA, whereas SGK1 inhibition via SGK1-shRNA improved neurocognitive function. The present study suggests the fundamental roles of SGK1 in brain circulation and neuronal survival/death in cerebral ischemia-related diseases.