{
  "abstract": "Introduction: Cerebral ischemia induces a reduction in brain pH. GPR4, a proton-sensing G protein-coupled receptor is highly expressed in vascular endothelial cells. Pharmacological inhibition of GPR4 with NE52-QQ57 (NEQQ) reduces ischemia-induced blood-brain barrier (BBB) disruption and brain injury. To facilitate targeting GPR4 in vivo, it is important to better define the effect of NEQQ on post-ischemia signaling and the pharmacokinetics of NEQQ in vivo. Methods: We performed biochemical analysis following transient middle cerebral artery occlusion (tMCAO). We used Liquid Chromatography-Mass spectrometry (LC-MS/MS) to quantify the concentration of NEQQ in serum, brain, and peripheral tissues. Results: NEQQ administration decreased the phosphorylation of PKA substrates, PKC substrates, ERK1/2, and CREB. LC-MS/MS analysis detected NEQQ in both ipsilateral and contralateral hemisphere of the brain at 5 h and 24 h after reperfusion, demonstrating that NEQQ crosses the BBB. In peripheral tissues, NEQQ exhibited highest level in kidney and lowest in the heart. In sham controls, average serum concentrations were ~4 and 0.9 g/g at 5 and 24 h, respectively. Following tMCAO, ipsilateral brain exhibited higher levels as compared to the contralateral side at 5 h while the difference diminished at 24 h. Conclusions: NEQQ attenuated the ischemia-induced activation of multiple signaling pathways. NEQQ exhibited broad distribution in peripheral organs, and its brain level was sufficient for GPR4 inhibition at 24 h after injection. These findings support the use of NEQQ as a pharmacological inhibitor of GPR4-mediated signaling following ischemic stroke.",
  "abstract_shown": true,
  "affiliations": [
    "Tulane University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "name": "S. Joshi"
    },
    {
      "name": "Y. Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "X.-m. Zha"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bgjdjgb3vdpe1.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.09.754558",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.09.754558v1.full",
  "id": "bgjdjgb3vdpe1",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.09.754558v1",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "openalex",
      "2808|Barrier Structure and Function Studies"
    ]
  ],
  "openalex": "W7221567105",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.09.754558v1.full.pdf",
  "pmcid": "PMC13742613",
  "pmid": null,
  "published": "2026-10-09",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bgjdjgb3vdpe1.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:18Z",
      "native_id": "10.64898/2026.10.09.754558",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.09.754558v1"
    },
    {
      "first_seen": "2026-11-09T15:20:34Z",
      "native_id": "PMC:PMC13742613",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13742613"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "NE52-QQ57 attenuates post-ischemia protein phosphorylation in the mouse brain",
  "title_text": "NE52-QQ57 attenuates post-ischemia protein phosphorylation in the mouse brain",
  "type": "preprint",
  "updated_at": "2026-11-09T15:20:34Z",
  "url": "https://research.draconitic.com/paper/bgjdjgb3vdpe1",
  "venue": "bioRxiv",
  "versions": []
}