{
  "abstract": "Excitotoxicity constitutes a core pathological mechanism in cerebral ischemia and other central nervous system disorders. Astrocytes serve as pivotal regulators of glutamate–glutamine cycle homeostasis and thereby play a critical role in mitigating excitotoxicity. This study established a rat thromboembolic stroke model via autologous thrombus induction and systematically investigated the mechanisms underlying adenosine-mediated neuroprotection through pharmacological modulation of the adenosine pathway using adenosine, dipyridamole, and selective adenosine receptor antagonists. Subsequently, light-sensitive opsin expression in astrocytes was driven by the GFAP promoter, enabling cell-type-specific optogenetic modulation of astrocyte activity. Our findings demonstrate that adenosine significantly attenuates cerebral injury in a rat model of thromboembolic stroke, with astrocytes identified as the primary cellular target. Adenosine elicits an anti-excitotoxic effect by coordinately upregulating GLT-1 protein expression and downregulating Cx43 protein expression in astrocytes, thereby regulating glutamate transport and diffusion. Moreover, our findings demonstrate that adenosine-mediated neuroprotection is significantly attenuated by SCH58261 but not by PSB1115. We conclude that the adenosine–A2A receptor system plays a critical role in the regulation of glutamate homeostasis.",
  "abstract_shown": true,
  "affiliations": [
    "College of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330004, China",
    "State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Cheng Yuan"
    },
    {
      "affs": [
        0
      ],
      "name": "Jixin Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Yazhi Chen"
    },
    {
      "affs": [
        1
      ],
      "name": "Liyuan Cui"
    },
    {
      "affs": [
        0
      ],
      "name": "Yingjiao Liu",
      "orcid": "0000-0003-1947-6415"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0dvthd3hdc0hy.bib",
  "cited_by": 0,
  "doi": "10.3390/cells15201915",
  "fulltext_url": "https://europepmc.org/articles/PMC13703560",
  "id": "0dvthd3hdc0hy",
  "issns": [
    "2073-4409"
  ],
  "landing_url": "https://www.mdpi.com/2073-4409/15/20/1915",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1314|Adenosine and Purinergic Signaling"
    ]
  ],
  "openalex": "W7223138671",
  "pdf_url": "https://europepmc.org/articles/PMC13703560?pdf=render",
  "pmcid": "PMC13703560",
  "pmid": "42929887",
  "published": "2026-10-21",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/0dvthd3hdc0hy.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:02Z",
      "native_id": "10.3390/cells15201915",
      "source": "crossref",
      "url": "https://www.mdpi.com/2073-4409/15/20/1915"
    },
    {
      "first_seen": "2026-10-30T12:22:01Z",
      "native_id": "MED:42929887",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42929887"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1314|Adenosine and Purinergic Signaling",
      "subfield": "physiology"
    }
  ],
  "title": "Adenosine-A2 Receptor Signaling in Astrocytes Mitigates Cerebral Ischemic Injury via Suppressing Glutamate-Induced Excitotoxicity",
  "title_text": "Adenosine-A2 Receptor Signaling in Astrocytes Mitigates Cerebral Ischemic Injury via Suppressing Glutamate-Induced Excitotoxicity",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:01Z",
  "url": "https://research.draconitic.com/paper/0dvthd3hdc0hy",
  "venue": "Cells",
  "versions": []
}