ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2017
Deletion of the WNK3-SPAK kinase complex in mice improves radiographic and clinical outcomes in malignant cerebral edema after ischemic stroke.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- No lysine? No problem: the surprising roles of WNK kinases in physiology and disease.The Biochemical journal · 2026Review
- Acupuncture improves neurological function in ICH rats via suppression of WNK-SPAK-NKCC1 signaling activation.Journal of molecular histology · 2026Article
- Oxidative Stress-Responsive 1 Kinase Catalytic Activity Promotes Triple Negative Breast Cancer Oncogenic Potential.ACS pharmacology & translational science · 2025Article
- Ion transporter cascade, reactive astrogliosis and cerebrovascular diseases.Frontiers in pharmacology · 2024Review
- Identification of a Class of WNK Isoform-Specific Inhibitors Through High-Throughput Screening.Drug design, development and therapy · 2023Article
- Efficacy of novel SPAK inhibitor ZT-1a derivatives (1c, 1d, 1g & 1h) on improving post-stroke neurological outcome and brain lesion in mice.Neurochemistry international · 2023Article
- Sequence and structural variations determining the recruitment of WNK kinases to the KLHL3 E3 ligase.The Biochemical journal · 2022Article
- WNK3 kinase maintains neuronal excitability by reducing inwardly rectifying KFrontiers in molecular neuroscience · 2022Article
- The Mitochondrial mitoNEET Ligand NL-1 Is Protective in a Murine Model of Transient Cerebral Ischemic Stroke.Pharmaceutical research · 2021Article
- High glucose-induced effects on NaAmerican journal of physiology. Cell physiology · 2021Article
- Galectin-3 protects against ischemic stroke by promoting neuro-angiogenesis via apoptosis inhibition and Akt/Caspase regulation.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- SPAK-p38 MAPK signal pathway modulates claudin-18 and barrier function of alveolar epithelium after hyperoxic exposure.BMC pulmonary medicine · 2021Article
- Targeting the WNK-SPAK/OSR1 Pathway and Cation-Chloride Cotransporters for the Therapy of Stroke.International journal of molecular sciences · 2021Review
- Modulation of brain cation-ClNature communications · 2020Article
- Physiological Processes Modulated by the Chloride-Sensitive WNK-SPAK/OSR1 Kinase Signaling Pathway and the Cation-Coupled Chloride Cotransporters.Frontiers in physiology · 2020Review
- The WNK-SPAK/OSR1 Kinases and the Cation-Chloride Cotransporters as Therapeutic Targets for Neurological Diseases.Aging and disease · 2019Review
- Sodium Valproate Ameliorates Neuronal Apoptosis in a Kainic Acid Model of Epilepsy via Enhancing PKC-Dependent GABANeurochemical research · 2018Article
- Selective role of NaGlia · 2018Article
- Selective knockout of astrocytic NaGlia · 2018Article
- WNK-Cab39-NKCC1 signaling increases the susceptibility to ischemic brain damage in hypertensive rats.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017Article
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Authors and funding
17 authors at 7 institutions in 3 countries.
Funding
Abstract
The WNK-SPAK kinase signaling pathway controls renal NaCl reabsorption and systemic blood pressure by regulating ion transporters and channels. A WNK3-SPAK complex is highly expressed in brain, but its function in this organ remains unclear. Here, we investigated the role of this kinase complex in brain edema and white matter injury after ischemic stroke. Wild-type, WNK3 knockout, and SPAK heterozygous or knockout mice underwent transient middle cerebral artery occlusion. One cohort of mice underwent magnetic resonance imaging. Ex-vivo brains three days post-ischemia were imaged by slice-selective spin-echo diffusion tensor imaging magnetic resonance imaging, after which the same brain tissues were subjected to immunofluorescence staining. A second cohort of mice underwent neurological deficit analysis up to 14 days post-transient middle cerebral artery occlusion. Relative to wild-type mice, WNK3 knockout, SPAK heterozygous, and SPAK knockout mice each exhibited a >50% reduction in infarct size and associated cerebral edema, significantly less demyelination, and improved neurological outcomes. We conclude that WNK3-SPAK signaling regulates brain swelling, gray matter injury, and demyelination after ischemic stroke, and that WNK3-SPAK inhibition has therapeutic potential for treating malignant cerebral edema in the setting of middle cerebral artery stroke.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.