ArticleScientific reports2022
Inhibition of HIF-1α-AQP4 axis ameliorates brain edema and neurological functional deficits in a rat controlled cortical injury (CCI) model.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 26 citations in OpenAlex.
- Aquaporin-4 mislocalization from astrocyte endfeet prolongs survival in a prion-cerebral amyloid angiopathy model.bioRxiv : the preprint server for biology · 2026Article
- Pathological changes and aquaporin-4 expression after bevacizumab treatment of traumatic penumbra in the rat brain.Scientific reports · 2025Article
- Perceiving traumatic brain injury from glymphatic system.Molecular psychiatry · 2025Review
- Aquaporin-4 in Stroke and Brain Edema-Friend or Foe?International journal of molecular sciences · 2025Review
- CB1 Receptor Activation Provides Neuroprotection in an Animal Model of Glutamate-Induced Excitotoxicity Through a Reduction of NOX-2 Activity and Oxidative Stress.CNS neuroscience & therapeutics · 2024Article
- Improvement in edema and cognitive recovery after moderate traumatic brain injury with the neurosteroid prodrug NTS-104.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Aquaporin 4 and the endocannabinoid system: a potential therapeutic target in brain injury.Experimental brain research · 2024Review
- Article
- [Expression and significance of hypoxia-inducible factor 1α and Bcl-2/adenovirus E1B19kDa-interacting protein 3 in children with traumatic brain injury].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2024Article
- TAK-3 Inhibits Lipopolysaccharide-Induced Neuroinflammation in Traumatic Brain Injury Rats Through the TLR-4/NF-κB Pathway.Journal of inflammation research · 2024Article
- Controlled Decompression Alleviates Motor Dysfunction by Regulating Microglial Polarization via the HIF-1α Signaling Pathway in Intracranial Hypertension.Molecular neurobiology · 2023Article
- Regional variances depict a unique glial-specific inflammatory response following closed-head injury.Frontiers in cellular neuroscience · 2023Article
- Cerebrospinal Fluid Hydrodynamics in Chiari I Malformation and Syringomyelia: Modeling Pathophysiology.Neurosurgery clinics of North America · 2023Review
- Tanshinone IIA reduces AQP4 expression and astrocyte swelling after OGD/R by inhibiting the HMGB1/RAGE/NF-κB/IL-6 pro-inflammatory axis.Scientific reports · 2022Article
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Authors and funding
9 authors at 4 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Traumatic brain injury (TBI) is an important cause of death in young adults and children. Till now, the treatment of TBI in the short- and long-term complications is still a challenge. Our previous evidence implied aquaporin 4 (AQP4) and hypoxia inducible factor-1α (HIF-1α) might be potential targets for TBI. In this study, we explored the roles of AQP4 and HIF-1α on brain edema formation, neuronal damage and neurological functional deficits after TBI using the controlled cortical injury (CCI) model. The adult male Sprague Dawley rats were randomly divided into sham and TBI group, the latter group was further divided into neutralized-AQP4 antibody group, 2-methoxyestradiol (2-ME2) group, and their corresponding control, IgG and isotonic saline groups, respectively. Brain edema was examined by water content. Hippocampal neuronal injury was assessed by neuron loss and neuronal skeleton related protein expressions. Spatial learning and memory deficits were evaluated by Morris water maze test and memory-related proteins were detected by western blot. Our data showed that increased AQP4 protein level was closely correlated with severity of brain edema after TBI. Compared with that in the control group, both blockage of AQP4 with neutralized-AQP4 antibody and inhibition of HIF-1α with 2-ME2 for one-time treatment within 30-60 min post TBI significantly ameliorated brain edema on the 1st day post-TBI, and markedly alleviated hippocampal neuron loss and spatial learning and memory deficits on the 21st day post-TBI. In summary, our preliminary study revealed the short-term and long-term benefits of targeting HIF-1α-AQP4 axis after TBI, which may provide new clues for the selection of potential therapeutic targets for TBI in clinical practice.
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