S-Nitrosylation of Dexras1 Controls Post-Stroke Recovery via Regulation of Neuronal Excitability and Dendritic Remodeling.

Aims: Stroke is a major public health concern leading to high rates of death and disability worldwide, unfortunately with no effective treatment available for stroke recovery during the repair phase.

Methods: Photothrombotic stroke was induced in mice. Adeno-associated viruses (AAV) were microinjected into the peri-infarct cortex immediately after photothrombotic stroke.

Nitric Oxide-Releasing Mesoporous Hollow Cerium Oxide Nanozyme-Based Hydrogel Synergizes with Neural Stem Cell for Spinal Cord Injury Repair.

Neural stem cell (NSCs) transplantation is a promising therapeutic strategy for spinal cord injury (SCI), but its efficacy is greatly limited by the local inhibitory microenvironment. In this study, based on l-arginine (l-Arg)-loaded mesoporous hollow cerium oxide (AhCeO) nanospheres, we constructed an injectable composite hydrogel (AhCeO-Gel) with microenvironment modulation capability. AhCeO-Gel protected NSCs from oxidative damage by eliminating excess reactive oxygen species while continuously delivering Nitric Oxide to the lesion of SCI in a pathological microenvironment, the latter of which effectively promoted the neural differentiation of NSCs.

Cedrol attenuates acute ischemic injury through inhibition of microglia-associated neuroinflammation via ERβ-NF-κB signaling pathways.

Microglia-associated neuroinflammation plays essential roles in pathology of acute stroke. Cedrol, a natural compound extracted from ginger, has been shown to confer inhibitory effects on inflammation in various diseases. However, whether Cedrol suppresses neuroinflammation and protects brains from acute ischemic injury still remains unclear.

Predictive value of white matter hyperintensity burden combined with collateral circulation in mechanical thrombectomy for acute anterior circulation large vessel occlusion.

Objective: To investigate the correlation and predictive value of white matter hyperintensity (WMH) burden in conjunction with collateral circulation during mechanical thrombectomy (MT) for acute anterior circulation occlusion.

Methods: A database comprising consecutive registrations of patients who underwent mechanical thrombectomy for acute anterior circulation large vessel occlusive cerebral infarction at Nanjing Drum Tower Hospital from January 2018 to December 2021 was analyzed. Collateral circulation was assessed using the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) scoring criteria.

Multi-systemic melioidosis in a patient with type 2 diabetes in non-endemic areas: A case report and review of literature.

Background: Melioidosis, an infectious disease caused by (), occurs endemically in Southeast Asia and Northern Australia and is a serious opportunistic infection associated with a high mortality rate.

Case Summary: A 58-year-old woman presented with scattered erythema on the skin of her limbs, followed by fever and seizures. i was isolated successively from the patient's urine, blood, and pus.

Association of tirofiban with improvement of functional outcomes of direct thrombectomy for acute anterior circulation occlusion: a retrospective, nonrandomized, multicenter, real-world study.

Objective: Although tirofiban and endovascular thrombectomy have been widely used in the treatment of acute ischemic stroke (AIS) patients, the effectiveness of their combined application remains a subject of debate. This study aimed to assess the efficacy and safety of tirofiban in direct thrombectomy for AIS with anterior circulation vessel occlusion.

Methods: A total of 204 patients undergoing direct thrombectomy between January 2020 and December 2021 for AIS with anterior circulation vessel occlusion from four hospitals were included in this study.

Fasting blood glucose-to-glycated hemoglobin ratio for evaluating clinical outcomes in patients with ischemic stroke.

Background: Stress hyperglycemia frequently occurs in patients with acute ischemic stroke (AIS). The influence of stress hyperglycemia on the outcomes of patients with AIS remains ambiguous.

Methods: Data from our institution on patients with AIS between June 2020 and June 2021 were retrospectively analyzed.

ROS-Scavenging Hydrogels Synergize with Neural Stem Cells to Enhance Spinal Cord Injury Repair via Regulating Microenvironment and Facilitating Nerve Regeneration.

Although stem cell-based therapy is recognized as a promising therapeutic strategy for spinal cord injury (SCI), its efficacy is greatly limited by local reactive oxygen species (ROS)-abundant and hyper-inflammatory microenvironments. It is still a challenge to develop bioactive scaffolds with outstanding antioxidant capacity for neural stem cells (NSCs) transplantation. In this study, albumin biomimetic cerium oxide nanoparticles (CeO @BSA nanoparticles, CeNPs) are prepared in a simple and efficient manner and dispersed in gelatin methacryloyl to obtain the ROS-scavenging hydrogel (CeNP-Gel).

Ketone bodies promote stroke recovery via GAT-1-dependent cortical network remodeling.

Stroke is a leading cause of adult disability worldwide, and better drugs are needed to promote functional recovery after stroke. Growing evidence suggests the critical role of network excitability during the repair phase for stroke recovery. Here, we show that β-hydroxybutyrate (β-HB), an essential ketone body (KB) component, is positively correlated with improved outcomes in patients with stroke and promotes functional recovery in rodents with stroke during the repair phase.

Identification of Pyroptosis-Relevant Signature in Tumor Immune Microenvironment and Prognosis in Skin Cutaneous Melanoma Using Network Analysis.

Background: Pyroptosis is closely related to the programmed death of cancer cells as well as the tumor immune microenvironment (TIME) via the host-tumor crosstalk. However, the role of pyroptosis-related genes as prognosis and TIME-related biomarkers in skin cutaneous melanoma (SKCM) patients remains unknown.

Methods: We evaluated the expression profiles, copy number variations, and somatic mutations (CNVs) of 27 genes obtained from MSigDB database regulating pyroptosis among TCGA-SKCM patients.

A Presurgical Unfavorable Prediction Scale of Endovascular Treatment for Acute Ischemic Stroke.

Objective: To develop a prognostic prediction model of endovascular treatment (EVT) for acute ischemic stroke (AIS) induced by large-vessel occlusion (LVO), this study applied machine learning classification model light gradient boosting machine (LightGBM) to construct a unique prediction model.

Methods: A total of 973 patients were enrolled, primary outcome was assessed with modified Rankin scale (mRS) at 90 days, and favorable outcome was defined using mRS 0-2 scores. Besides, LightGBM algorithm and logistic regression (LR) were used to construct a prediction model.

Atorvastatin ameliorates depressive behaviors via regulation of α7nAChR expression by PI3K/Akt-BDNF pathway in mice.

Some of the statins have been shown to have antidepressant effects, but whether atorvastatin (AV) has antidepressant effects is unknown. This study was to investigate the effect of AV treatment on depressive behaviors. Herein, we show that AV treatment had antidepressant-like effect in physiological conditions and antidepressant effect in depressive state which depended on α7 nicotinic acetylcholine receptor (α7nAChR) expression in the ventral hippocampus (vHPC), but not α4β2 nicotinic acetylcholine receptor (α4β2nAchR) expression in vHPC, nor the α7nAChR and α4β2nAchR expression in dorsal hippocampus (dHPC).

Mesencephalic astrocyte-derived neurotrophic factor restores blood-brain barrier integrity of aged mice after ischaemic stroke/reperfusion through anti-inflammation via TLR4/MyD88/NF-κB pathway.

Ischaemic stroke remains a leading cause of disability and mortality worldwide and ageing-associated inflammation for the aged patients specifically leads to worse post-stroke blood-brain barrier (BBB) disruption than young subjects. Accordingly, suppression of excessive inflammation can alleviate BBB injury, which provides potential therapeutic treatment for ischaemic stroke of the aged. Prior studies revealed that mesencephalic astrocyte-derived neurotrophic factor (MANF) regulated inflammatory response and alleviated liver injury in ageing.

Environmental enrichment implies GAT-1 as a potential therapeutic target for stroke recovery.

Stroke is a leading cause of adult disability worldwide, but no drug provides functional recovery during the repair phase. Accumulating evidence demonstrates that environmental enrichment (EE) promotes stroke recovery by enhancing network excitability. However, the complexities of utilizing EE in a clinical setting limit its translation.

Dissociating nNOS (Neuronal NO Synthase)-CAPON (Carboxy-Terminal Postsynaptic Density-95/Discs Large/Zona Occludens-1 Ligand of nNOS) Interaction Promotes Functional Recovery After Stroke via Enhanced Structural Neuroplasticity.

Background and Purpose- Stroke is a major public health concern worldwide. Although clinical treatments have improved in the acute period after stroke, long-term therapeutics remain limited to physical rehabilitation in the delayed phase. This study is aimed to determine whether nNOS (neuronal NO synthase)-CAPON (carboxy-terminal postsynaptic density-95/discs large/zona occludens-1 ligand of nNOS) interaction may serve as a new therapeutic target in the delayed phase for stroke recovery.

2-Methyl-5H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine, an edaravone analog, exerts neuroprotective effects against acute ischemic injury via inhibiting oxidative stress.

Oxidative stress plays an indispensable role in the pathogenesis of cerebral ischemia. Inhibiting oxidative stress has been considered as an effective approach for stroke treatment. Edaravone, a free radical scavenger, has been shown to prevent cerebral ischemic injury.

Hippocampal nuclear factor kappa B accounts for stress-induced anxiety behaviors via enhancing neuronal nitric oxide synthase (nNOS)-carboxy-terminal PDZ ligand of nNOS-Dexras1 coupling.

Anxiety disorders are associated with a high social burden worldwide. Recently, increasing evidence suggests that nuclear factor kappa B (NF-κB) has significant implications for psychiatric diseases, including anxiety and depressive disorders. However, the molecular mechanisms underlying the role of NF-κB in stress-induced anxiety behaviors are poorly understood.

nNOS-CAPON interaction mediates amyloid-β-induced neurotoxicity, especially in the early stages.

In neurons, increased protein-protein interactions between neuronal nitric oxide synthase (nNOS) and its carboxy-terminal PDZ ligand (CAPON) contribute to excitotoxicity and abnormal dendritic spine development, both of which are involved in the development of Alzheimer's disease. In models of Alzheimer's disease, increased nNOS-CAPON interaction was detected after treatment with amyloid-β in vitro, and a similar change was found in the hippocampus of APP/PS1 mice (a transgenic mouse model of Alzheimer's disease), compared with age-matched background mice in vivo. After blocking the nNOS-CAPON interaction, memory was rescued in 4-month-old APP/PS1 mice, and dendritic impairments were ameliorated both in vivo and in vitro.

(+)-Borneol suppresses conditioned fear recall and anxiety-like behaviors in mice.

Fear- and anxiety-related psychiatric disorders have been one of the major chronic diseases afflicting patients for decades, and new compounds for treating such disorders remain to be developed. (+)-Borneol, a bicyclic monoterpene found in several species of Artemisia and Dipterocarpaceae, is widely used for anxiety, pain and anesthesia in Chinese medicine. Meanwhile, it can potentiate GABA (γ-aminobutyric acid) activity directly in recombinant GABAA receptors.

Dissociation of nNOS from PSD-95 promotes functional recovery after cerebral ischaemia in mice through reducing excessive tonic GABA release from reactive astrocytes.

Mechanisms underlying functional recovery after stroke are little known, and effective drug intervention during the delayed stage is desirable. One potential drug target, the protein-protein interaction between neuronal nitric oxide synthase (nNOS) and postsynaptic density protein 95 (PSD-95), is critical to acute ischaemic damage and neurogenesis. We show that nNOS-PSD-95 dissociation induced by microinjection of a recombinant fusion protein, Tat-nNOS-N , or systemic administration of a small-molecule, ZL006, from day 4 to day 10 after photothrombotic ischaemia in mice reduced excessive tonic inhibition in the peri-infarct cortex and ameliorated motor functional outcome.

Inhibiting Histone Deacetylase 2 (HDAC2) Promotes Functional Recovery From Stroke.

Background: Stroke is a leading cause of long-term disability worldwide. However, current therapies that promote functional recovery from stroke are limited to physical rehabilitation. No pharmacological therapy is available.

MGE-derived nNOS interneurons promote fear acquisition in nNOS mice.

Neuronal nitric oxide synthase (nNOS) , mainly responsible for NO release in central nervous system (CNS) , plays a significant role in multiple physiological functions. However, the function of nNOS interneurons in fear learning has not been much explored. Here we focused on the medial ganglionic eminences (MGE) -derived nNOS interneurons in fear learning.

Opening a New Time Window for Treatment of Stroke by Targeting HDAC2.

Narrow therapeutic window limits treatments with thrombolysis and neuroprotection for most stroke patients. Widening therapeutic window remains a critical challenge. Understanding the key mechanisms underlying the pathophysiological events in the peri-infarct area where secondary injury coexists with neuroplasticity over days to weeks may offer an opportunity for expanding the therapeutic window.