ArticlePloS one2017
Ceftriaxone- and N-acetylcysteine-induced brain tolerance to ischemia: Influence on glutamate levels in focal cerebral ischemia.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 60 citations in OpenAlex.
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- A single extinction-based treatment with N-Acetylcysteine produces long-term reduction in cocaine relapse.Translational psychiatry · 2026Article
- The mTOR/Akt pathway is involved in regulating astrocyte growth and GLT-1 expression during cerebral ischemia-reperfusion.PloS one · 2026Article
- Metabolic Regulatory Networks in Ferroptosis During Alzheimer's Disease, Mechanisms of Glial Cell Action, and Pathological Correlations with Neuritic Plaques.International journal of general medicine · 2026Review
- Adenosine ANeuropharmacology · 2025Article
- Plasma Cystine as a Marker of Acute Stroke Severity.Diagnostics (Basel, Switzerland) · 2025Article
- The Central Nervous System Modulatory Activities of N-Acetylcysteine: A Synthesis of Two Decades of Evidence.Current issues in molecular biology · 2025Review
- Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects.Signal transduction and targeted therapy · 2024Review
- Cysteine induces mitochondrial reductive stress in glioblastoma through hydrogen peroxide production.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- HSP90β regulates EAAT2 expression and participates in ischemia‑reperfusion injury in rats.Molecular medicine reports · 2024Article
- Questioning Glutamate Excitotoxicity in Acute Brain Damage: The Importance of Spreading Depolarization.Neurocritical care · 2022Article
- Identification of optimal reference genes for gene expression studies in a focal cerebral ischaemia model-Spatiotemporal effects.Journal of cellular and molecular medicine · 2022Article
- Article
- A New Player in the Hippocampus: A Review on VGLUT3+ Neurons and Their Role in the Regulation of Hippocampal Activity and Behaviour.International journal of molecular sciences · 2022Review
- Ferroptosis-A Novel Mechanism With Multifaceted Actions on Stroke.Frontiers in neurology · 2022Review
- Pathways Involved in Remyelination after Cerebral Ischemia.Current neuropharmacology · 2022Article
- Ceftriaxone as a Novel Therapeutic Agent for Hyperglutamatergic States: Bridging the Gap Between Preclinical Results and Clinical Translation.Frontiers in neuroscience · 2022Review
- Potential application of traditional Chinese medicine in cerebral ischemia-Focusing on ferroptosis.Frontiers in pharmacology · 2022Review
- The Slow-Releasing and Mitochondria-Targeted Hydrogen Sulfide (HInternational journal of molecular sciences · 2021Article
- Potential Benefits of N-Acetylcysteine in Preventing Pregabalin-Induced Seeking-Like Behavior.Healthcare (Basel, Switzerland) · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
One of the major players in the pathophysiology of cerebral ischemia is disrupted homeostasis of glutamatergic neurotransmission, resulting in elevated extracellular glutamate (Glu) concentrations and excitotoxicity-related cell death. In the brain, Glu concentrations are regulated by Glu transporters, including Glu transporter-1 (GLT-1) and cystine/Glu antiporter (system xc-). Modulation of these transporters by administration of ceftriaxone (CEF, 200 mg/kg, i.p.) or N-acetylcysteine (NAC, 150 mg/kg, i.p.) for 5 days before focal cerebral ischemia may induce brain tolerance to ischemia by significantly limiting stroke-related damage and normalizing Glu concentrations. In the present study, focal cerebral ischemia was induced by 90-minute middle cerebral artery occlusion (MCAO). We compared the effects of CEF and NAC pretreatment on Glu concentrations in extracellular fluid and cellular-specific expression of GLT-1 and xCT with the effects of two reference preconditioning methods, namely, ischemic preconditioning and chemical preconditioning in rats. Both CEF and NAC significantly reduced Glu levels in the frontal cortex and hippocampus during focal cerebral ischemia, and this decrease was comparable with the Glu level achieved with the reference preconditioning strategies. The results of immunofluorescence staining of GLT-1 and xCT on astrocytes, neurons and microglia accounted for the observed changes in extracellular Glu levels to a certain extent. Briefly, after MCAO, the expression of GLT-1 on astrocytes decreased, but pretreatment with CEF seemed to prevent this downregulation. In addition, every intervention used in this study seemed to reduce xCT expression on astrocytes and neurons. The results of this study indicate that modulation of Glu transporter expression may restore Glu homeostasis. Moreover, our results suggest that CEF and NAC may induce brain tolerance to ischemia by influencing GLT-1 and system xc- expression levels. These transporters are presumably good targets for the development of novel therapies for brain ischemia.
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