ArticlePflugers Archiv : European journal of physiology2015
NKCC1 mediates traumatic brain injury-induced hippocampal neurogenesis through CREB phosphorylation and HIF-1α expression.
Article in Pflugers Archiv : European journal of physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- The utilization of small non-mammals in traumatic brain injury research: A systematic review.CNS neuroscience & therapeutics · 2021Pooled it
- Hypoxia inducible factor-1α-driven signaling networks regulating adult neurogenesis via Notch, Wnt, and MAPK pathways.Molecular biology reports · 2026Review
- The pCREB/BDNF Pathway in the Hippocampus Is Involved in the Therapeutic Effect of Selective 5-HT Reuptake Inhibitors in Adult Male Rats Exposed to Blast Traumatic Brain Injury.Brain sciences · 2025Article
- Effect of Bevacizumab on traumatic penumbra brain edema in rats at different time points.Tissue barriers · 2024Article
- Overabundant endocannabinoids in neurons are detrimental to cognitive function.bioRxiv : the preprint server for biology · 2024Article
- Microglia-induced neuroinflammation in hippocampal neurogenesis following traumatic brain injury.Heliyon · 2024Review
- Review
- HIF-1α participates in secondary brain injury through regulating neuroinflammation.Translational neuroscience · 2023Article
- A Novel Laser-Based Zebrafish Model for Studying Traumatic Brain Injury and Its Molecular Targets.Pharmaceutics · 2022Article
- On the potential role of globins in brown adipose tissue: a novel conceptual model and studies in myoglobin knockout mice.American journal of physiology. Endocrinology and metabolism · 2021Article
- Targeting the WNK-SPAK/OSR1 Pathway and Cation-Chloride Cotransporters for the Therapy of Stroke.International journal of molecular sciences · 2021Review
- Effects of Selective Serotonin Reuptake Inhibitors on Depression-Like Behavior in a Laser-Induced Shock Wave Model.Frontiers in neurology · 2021Article
- Neuronal Transmembrane Chloride Transport Has a Time-Dependent Influence on Survival of Hippocampal Cultures to Oxygen-Glucose Deprivation.Brain sciences · 2019Article
- Relationship between HIF-1α and apoptosis in rats with traumatic brain injury and the influence of traditional Chinese medicine Sanqi.Saudi journal of biological sciences · 2019Article
- Predator stress-induced depression is associated with inhibition of hippocampal neurogenesis in adult male mice.Neural regeneration research · 2019Article
- NFAT5 and HIF-1α Coordinate to Regulate NKCC1 Expression in Hippocampal Neurons After Hypoxia-Ischemia.Frontiers in cell and developmental biology · 2019Article
- Kir6.2 Deficiency Promotes Mesencephalic Neural Precursor Cell Differentiation via Regulating miR-133b/GDNF in a Parkinson's Disease Mouse Model.Molecular neurobiology · 2018Article
- Inhibition of NKCC1 Modulates Alveolar Fluid Clearance and Inflammation in Ischemia-Reperfusion Lung Injury via TRAF6-Mediated Pathways.Frontiers in immunology · 2018Article
- Activation of Sphingosine 1-Phosphate Receptor 1 Enhances Hippocampus Neurogenesis in a Rat Model of Traumatic Brain Injury: An Involvement of MEK/Erk Signaling Pathway.Neural plasticity · 2016Article
- Scaffolding protein Homer1a protects against NMDA-induced neuronal injury.Cell death & disease · 2015Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Traumatic brain injury (TBI) is one of the most prevalent causes of worldwide mortality and morbidity. We previously had evidenced that TBI induced Na-K-2Cl co-transporter (NKCC1) upregulation in hippocampus. Here, we aim to investigate the role of NKCC1 in TBI-induced neurogenesis and the detailed mechanisms. The TBI-associated alternations in the expression of NKCC1, HIF-1α, VEGF, MAPK cascade, and CREB phosphorylation were analyzed by Western blot. TBI-induced neurogenesis was determined by immuno-fluorescence labeling. Chromatin immunoprecipitation was used to elucidate whether HIF-1α would activate VEGF gene after TBI. We found that the level of hippocampal NKCC1 and VEGF began to rise 8 h after TBI, and both of them reached maxima at day 7. Along with the upregulation of NKCC1 and VEGF, MAPK cascade was activated and hippocampal neurogenesis was promoted. Administration of CREB antisense oligonucleotide significantly attenuated the expression of HIF-1α, while HIF-1α antisense oligonucleotide exhibited little effect on the expression of CREB. However, HIF-1α antisense oligonucleotide administration did effectively suppress the expression of VEGF. Our results of the chromosome immunoprecipitation also indicated that HIF-1α could directly act on the VEGF promoter and presumably would elevate the VEGF expression after TBI. All these results have illustrated the correlation between NKCC1 upregulation and TBI-associated neurogenesis. The pathway involves the activation of Raf/MEK/ERK cascade, CREB phosphorylation, and HIF-1α upregulation, and finally leads to the stimulation of VEGF expression and the induction of neurogenesis.
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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.