ArticleCNS neuroscience & therapeutics2024
SPAK inhibitor ZT-1a attenuates reactive astrogliosis and oligodendrocyte degeneration in a mouse model of vascular dementia.
Article in CNS neuroscience & therapeutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 11 citations in OpenAlex.
- Adiponectin Fortifies White Matter After Chronic Hypoperfusion-Induced Vascular Dementia.Stroke · 2026Article
- Decoding Dementia Mechanisms: Identification of Key Oligodendrocyte- Associated Genes through Integrative Bioinformatics and Machine Learning.Current topics in medicinal chemistry · 2026Article
- Article
- Pharmacological inhibition of SPAK-NKCC1 complex attenuates astrogliosis and restores cerebral blood flow in a mouse model of VCID.Acta neuropathologica communications · 2025Article
- Target inhibition of SPAK in choroid plexus attenuates T cell infiltration and demyelination in experimental autoimmune encephalomyelitis.Journal of neuroinflammation · 2025Article
- Edaravone dexborneol alleviates pericyte-mediated fibrosis depositing extracellular matrix through TGF-β1/IL-11 in cerebral small vessel disease.Journal of translational medicine · 2025Article
- The Phenotype Changes of Astrocyte During Different Ischemia Conditions.Brain sciences · 2024Article
- Carotid artery vascular stenosis causes the blood-CSF barrier damage and neuroinflammation.Journal of neuroinflammation · 2024Article
- SPAK inhibitor ZT-1a attenuates reactive astrogliosis and oligodendrocyte degeneration in a mouse model of vascular dementia.CNS neuroscience & therapeutics · 2024Article
- Ion transporter cascade, reactive astrogliosis and cerebrovascular diseases.Frontiers in pharmacology · 2024Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundAstrogliosis and white matter lesions (WML) are key characteristics of vascular contributions to cognitive impairment and dementia (VCID). However, the molecular mechanisms underlying VCID remain poorly understood. Stimulation of Na-K-Cl cotransport 1 (NKCC1) and its upstream kinases WNK (with no lysine) and SPAK (the STE20/SPS1-related proline/alanine-rich kinase) play a role in astrocytic intracellular Na
methodsFollowing sham or BCAS surgery, mice were randomly assigned to receive either vehicle (DMSO) or SPAK inhibitor ZT-1a treatment regimen (days 14-35 post-surgery). Mice were then evaluated for cognitive functions by Morris water maze, WML by ex vivo MRI-DTI analysis, and astrogliosis/demyelination by immunofluorescence and immunoblotting.
resultsCompared to sham control mice, BCAS-Veh mice exhibited chronic cerebral hypoperfusion and memory impairments, accompanied by significant MRI DTI-detected WML and oligodendrocyte (OL) death. Increased activation of WNK-SPAK-NKCC1-signaling proteins was detected in white matter tissues and in C3d
conclusionBCAS-induced upregulation of WNK-SPAK-NKCC1 signaling contributes to white matter-reactive astrogliosis, OL death, and memory impairment. Pharmacological inhibition of the SPAK activity has therapeutic potential for alleviating pathogenesis and memory impairment in VCID.
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