Na-K-ATPase/GLT-1 interaction participates in EGCG protection against cerebral ischemia-reperfusion injury in rats.

Background: In China, stroke is the primary cause of adult death and disability. Because of the increased rate of blood vessel reperfusion, it is important to prevent cerebral ischemia-reperfusion injury, in which glutamate (Glu) excitotoxicity plays a critical role. The most important Glu transporter, GLT-1, is essential for the regulation of Glu, which is dependent on Na-K-ATPase (NKA)-induced ion concentration gradient differences.

The AGEs/RAGE Signaling Pathway Regulates NLRP3-Mediated Neuronal Pyroptosis After MCAO Injury in Obese Rats.

Background: Obesity is recognized as a primary risk factor for cerebral ischemia, which has shown a significant increase in its incidence among obese patients. The exact mechanism by which obesity exacerbates cerebral ischemic injury is not fully understood though. The present study validated the hypothesis that obesity mediates pyroptosis by the AGEs/RAGE signaling pathway to exacerbate cerebral ischemic injury.

Sodium butyrate improves cognitive dysfunction in high-fat diet/ streptozotocin-induced type 2 diabetic mice by ameliorating hippocampal mitochondrial damage through regulating AMPK/PGC-1α pathway.

Cognitive dysfunction is an important comorbidity of type 2 diabetes mellitus (T2DM). Sodium butyrate (NaB) is a short-chain fatty acid and has an effect improving T2DM-associated cognitive dysfunction. Using a high-fat diet (HFD)/streptozotocin (STZ)-induced T2DM mouse model, the present study investigated the mechanism involved in the beneficial effect of butyrate on diabetic cognitive dysfunction, with a focus on ameliorating mitochondrial damage through regulating the adenosine monophosphate-activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1α (AMPK/PGC-1α) pathway considering the important role of mitochondrial impairments in the occurrence of T2DM-associated cognitive dysfunction.

The Downregulation of ITGAX Exacerbates Amyloid-β Plaque Deposition in Alzheimer's Disease by Increasing Polarization of M1 Microglia.

Background: Alzheimer's disease (AD) is the most common sort of neurodegenerative dementia, characterized by its challenging, diverse, and progressive nature. Despite significant progress in neuroscience, the current treatment strategies remain suboptimal.

Objective: Identifying a more accurate molecular target for the involvement of microglia in the pathogenic process of AD and exploring potential mechanisms via which it could influence disease.

Transformation of A1/A2 Astrocytes Participates in Brain Ischemic Tolerance Induced by Cerebral Ischemic Preconditioning via Inhibiting NDRG2.

Cerebral ischemic preconditioning (CIP) has been shown to improve brain ischemic tolerance against subsequent lethal ischemia. Reactive astrocytes play important roles in cerebral ischemia-reperfusion. Recent studies have shown that reactive astrocytes can be polarized into neurotoxic A1 phenotype (C3d) and neuroprotective A2 phenotype (S100A10).

Ceftriaxone Modulates Ubiquitination of α-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionic Acid Receptors to Improve Long-Term Potentiation Impairment Induced by Exogenous β-Amyloid in a Glutamate Transporter-1 Dependent Manner.

Α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) are crucial for properties of synaptic plasticity, such as long-term potentiation (LTP). LTP impairment can occur early in the onset of Alzheimer's disease (AD). The downregulation or decreased abundance of AMPAR expression in the postsynaptic membrane is closely associated with LTP impairment.

The Role of Astrocytic Mitochondria in the Pathogenesis of Brain Ischemia.

The morbidity rate of ischemic stroke is increasing annually with the growing aging population in China. Astrocytes are ubiquitous glial cells in the brain and play a crucial role in supporting neuronal function and metabolism. Increasing evidence shows that the impairment or loss of astrocytes contributes to neuronal dysfunction during cerebral ischemic injury.

Catalpol rescues cognitive deficits by attenuating amyloid β plaques and neuroinflammation.

Unlabelled: This study sought to investigate the anti-amyloid β (Aβ) and anti-neuroinflammatory effects of catalpol in an Alzheimer's disease (AD) mouse model.

Methods: The effects of catalpol on Aβ formation were investigated by thioflavin T assay. The effect of catalpol on generating inflammatory cytokines from microglial cells and the cytotoxicity of microglial cells on HT22 hippocampal cells were assessed by real-time quantitative PCR, ELISA, redox reactions, and cell viability.

Ceftriaxone ameliorates hippocampal synapse loss by inhibiting microglial/macrophages activation in glial glutamate transporter-1 dependent manner in the APP/PS1 mouse model of Alzheimer's disease.

Synapse loss is a major contributor to cognitive dysfunction in Alzheimer's disease (AD). Impairments in the expression and/or glutamate uptake activity of glia glutamate transporter-1 (GLT-1) contribute to synapse loss in AD. Hence, targeting the restoration of GLT-1 activity may have potential for alleviating synapse loss in AD.

Ceftriaxone improves impairments in synaptic plasticity and cognitive behavior in APP/PS1 mouse model of Alzheimer's disease by inhibiting extrasynaptic NMDAR-STEP signaling.

Abnormal activation of the extrasynaptic N-methyl-d-aspartate receptor (NMDAR) contributes to the pathogenesis of Alzheimer's disease (AD). Ceftriaxone (Cef) can improve cognitive impairment by upregulating glutamate transporter-1 and promoting the glutamate-glutamine cycle in an AD mouse model. This study aimed to investigate the effects of Cef on synaptic plasticity and cognitive-behavioral impairment and to unravel the associated underlying mechanisms.

The Role of Iron Metabolism, Lipid Metabolism, and Redox Homeostasis in Alzheimer's Disease: from the Perspective of Ferroptosis.

In the development of Alzheimer's disease (AD), cell death is common. Novel cell death form-ferroptosis is discovered in recent years. Ferroptosis is an iron-regulated programmed cell death mechanism and has been identified in AD clinical samples.

Sevoflurane exposure causes neuronal apoptosis and cognitive dysfunction by inducing ER stress activation of the inositol 1, 4, 5-trisphosphate receptor.

The role of the inositol 1, 4, 5-trisphosphate receptor (IP3R) in hippocampal neuronal apoptosis and cognitive dysfunction induced by sevoflurane is currently unclear. Therefore, in this study, we investigated the role of the IP3R in endoplasmic reticulum (ER) stress and hippocampal neuronal apoptosis induced by sevoflurane in aged rats and isolated hippocampal neurons using both and experiments, including bioinformatics, functional enrichment analysis, gene set enrichment analysis, hematoxylin, and eosin staining, TUNEL assay, flow cytometry, western blot analysis and transmission electron microscopy. Furthermore, behavioral assessment was performed with the Morris water maze test.

[Effects of exogenous hydrogen sulfide on pulmonary hypertension in rabbits with endotoxic shock].

To investigate the effects of exogenous hydrogen sulfide (HS) on pulmonary vascular reactivity induced by endotoxic shock (ES) in rabbits. In this experiment, the model of endotoxic shock (ES) was induced by injection of lipopolysaccharides (LPS) to New Zealand big eared white rabbit through jugular vein (8 mg/0.8 ml/kg), the intervention was performed by HS donor(sodium hydrosulfide, NaHS) which was injected intraperitoneally (28 μmol/kg) 15 min in advance.

Toll-Like Receptor 4: A Promising Therapeutic Target for Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that primarily manifests as memory deficits and cognitive impairment and has created health challenges for patients and society. In AD, amyloid -protein (A) induces Toll-like receptor 4 (TLR4) activation in microglia. Activation of TLR4 induces downstream signaling pathways and promotes the generation of proinflammatory cytokines, such as tumor necrosis factor- (TNF-), interleukin-6 (IL-6), and interleukin-1 (IL-1), which also trigger the activation of astrocytes and influence amyloid-dependent neuronal death.

The Regulation of Autophagy by p38 MAPK-PPARγ Signaling During the Brain Ischemic Tolerance Induced by Cerebral Ischemic Preconditioning.

Several studies indicated that autophagy activation participates in brain ischemic tolerance (BIT) induced by cerebral ischemic preconditioning (CIP). However, the mechanism of autophagy activation during the process still remains unclear. The present study aimed to evaluate the role of p38 MAPK-peroxisome proliferator-activated receptor γ (PPARγ) signaling cascade in autophagy during the CIP-induced BIT.

Klotho Upregulation via PPARγ Contributes to the Induction of Brain Ischemic Tolerance by Cerebral Ischemic Preconditioning in Rats.

Cerebral ischemic preconditioning (CIP)-induced brain ischemic tolerance protects neurons from subsequent lethal ischemic insult. However, the specific mechanisms underlying CIP remain unclear. In the present study, we explored the hypothesis that peroxisome proliferator-activated receptor gamma (PPARγ) participates in the upregulation of Klotho during the induction of brain ischemic tolerance by CIP.

Ceftriaxone Suppresses Group II Metabotropic Glutamate Receptor Expression Contributing to Reversal of Recognition Memory Deficits of Amyloid Precursor Protein/Presenilin 1 AD Mice.

Group II metabotropic glutamate receptors (Group II mGluRs) are the peri-synaptic receptor of glutamatergic neurons and negatively regulate glutamate release from presynaptic neurons. Glutamate in the synaptic cleft is mainly taken into astrocytes by glutamate transporter-1 (GLT-1), which is primarily expressed in astrocytes. Increasing evidence showed that inhibiting or suppressing the activation of Group II mGluRs would contribute to the improvement of learning and memory deficits in Alzheimer's disease (AD) animal models.

Effects of ω-3 Polyunsaturated Fatty Acids on Coronary Atherosclerosis and Inflammation: A Systematic Review and Meta-Analysis.

Background And Purpose: Multiple guidelines suggest the ω-3 polyunsaturated fatty acids (ω-3 PUFAs) help to prevent major vascular events of coronary heart disease (CHD), but the data on large trials of ω-3 fatty acids are controversial. We reviewed the available evidence to determine the effect of ω-3 PUFAs on coronary atherosclerosis.

Materials And Methods: Literature were from online databases.

IL-17A deletion reduces sevoflurane-induced neurocognitive impairment in neonatal mice by inhibiting NF-κB signaling pathway.

We investigated the role of IL-17A in sevoflurane-inducedneurocognitive impairment in neonatal mice. Seventy-two wild-type (WT) and 42 IL-17A knockout (KO) neonatal mice were randomly divided into WT ( = 36), IL-17A ( = 6), sevoflurane (Sev, = 36), and IL-17A + sevoflurane (IL-17A + Sev, = 36) groups. The latter two groups were given 3% sevoflurane for 2 h per day on postnatal days (P) 6-8.

LncRNA BIRF Promotes Brain Ischemic Tolerance Induced By Cerebral Ischemic Preconditioning Through Upregulating GLT-1 via Sponging miR-330-5p.

Long noncoding RNAs (lncRNAs) play an important regulatory role in various diseases. However, the role of lncRNAs in brain ischemic tolerance (BIT) induced by cerebral ischemic preconditioning (CIPC) is still unknown. The lncRNA profile of rat cortical astrocytes pretreated with ischemic preconditioning was analyzed by high-throughput sequencing.

Sulbactam improves binding property and uptake capacity of glutamate transporter-1 and decreases glutamate concentration in the CA1 region of hippocampus of global brain ischemic rats.

Glutamate transporter-1 (GLT-1) removes most glutamate in the synaptic cleft. Sulbactam confers neuronal protection against ischemic insults in the hippocampal CA1 region accompanied by the upregulation of GLT-1 expression in rats. The present study further investigates the effect of sulbactam on the binding property and uptake capacity of GLT-1 for glutamate, and the change in extracellular glutamate concentration in the hippocampal CA1 region of rats with global brain ischemia.

The p38 MAPK/NF-κB pathway mediates GLT-1 up-regulation during cerebral ischemic preconditioning-induced brain ischemic tolerance in rats.

Our previous finding suggests that p38 MAPK contributes to the GLT-1 upregulation during induction of brain ischemic tolerance by cerebral ischemic preconditioning (CIP), however, the underlying mechanism is still unclear. Here, we investigated the molecular mechanisms underlying the CIP-induced GLT-1 upregulation by using Western blotting, Co-immunoprecipitation (Co-IP), electrophoretic mobility shift assay (EMSA) and thionin staining in rat hippocampus CA1 subset. We found that application of BAY11-7082 (an inhibitor of NF-κB), or dihydrokainate (an inhibitor of GLT-1), or SB203580 (an inhibitor of p38 MAPK) could attenuate the CIP-induced neuronal protection in hippocampus CA1 region of rats.

Ceftriaxone regulates glutamate production and vesicular assembly in presynaptic terminals through GLT-1 in APP/PS1 mice.

Perturbations in the glutamate-glutamine cycle and glutamate release from presynaptic terminals have been involved in the development of cognitive deficits in Alzheimer's disease (AD) patients and mouse models. Glutamate transporter-1 (GLT-1) removes glutamate from the synaptic cleft and transports it into astrocytes, where it is used as substrate for the glutamate-glutamine cycle. Ceftriaxone has been reported to improve cognitive deficits in AD mice by increasing GLT-1 expression, glutamate transformation to glutamine, and glutamine efflux from astrocytes.