ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2014
Greatly improved survival and neuroprotection in aquaporin-4-knockout mice following global cerebral ischemia.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 85 citations in OpenAlex.
- Diffusion Tensor Imaging Along the Perivascular Space in Veterans with Remote Mild Traumatic Brain Injuries.Journal of neurotrauma · 2026Article
- Research progress on biomarkers of traumatic brain injury.Animal models and experimental medicine · 2026Review
- Aquaporins in Acute Brain Injury: Insights from Clinical and Experimental Studies.Biomedicines · 2025Review
- Early Increase in Blood-Brain Barrier Permeability in a Murine Model Exposed to Fifteen Days of Intermittent Hypoxia.International journal of molecular sciences · 2024Article
- The glymphatic system's role in traumatic brain injury-related neurodegeneration.Molecular psychiatry · 2023Review
- The Diversity of Astrocyte Activation during Multiple Sclerosis: Potential Cellular Targets for Novel Disease Modifying Therapeutics.Healthcare (Basel, Switzerland) · 2023Review
- Molecular mechanism of cerebral edema improvement via IL-1RA released from the stroke-unaffected hindlimb by treadmill exercise after cerebral infarction in rats.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- A primordial target: Mitochondria mediate both primary and collateral anesthetic effects of volatile anesthetics.Experimental biology and medicine (Maywood, N.J.) · 2023Review
- Loss of aquaporin-4 results in glymphatic system dysfunction via brain-wide interstitial fluid stagnation.eLife · 2023Article
- Aquaporins in Cardiovascular System.Advances in experimental medicine and biology · 2023Article
- Tetramethylpyrazine promotes stroke recovery by inducing the restoration of neurovascular unit and transformation of A1/A2 reactive astrocytes.Frontiers in cellular neuroscience · 2023Article
- The meningeal lymphatic vessels and the glymphatic system: Potential therapeutic targets in neurological disorders.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Review
- Acetazolamide Alleviate Cerebral Edema Induced by Ischemic Stroke Through Inhibiting the Expression of AQP4 mRNA.Neurocritical care · 2022Article
- The absence of AQP4/TRPV4 complex substantially reduces acute cytotoxic edema following ischemic injury.Frontiers in cellular neuroscience · 2022Article
- Roles of Micro Ribonucleic Acids in Astrocytes After Cerebral Stroke.Frontiers in cellular neuroscience · 2022Review
- Protective Effects of Aquaporin-4 Deficiency on Longer-term Neurological Outcomes in a Mouse Model.Neurochemical research · 2021Article
- The Glymphatic System: A Novel Therapeutic Target for Stroke Treatment.Frontiers in aging neuroscience · 2021Review
- Cerebral Microcirculation, Perivascular Unit, and Glymphatic System: Role of Aquaporin-4 as the Gatekeeper for Water Homeostasis.Frontiers in neurology · 2021Review
- Hypertonic saline improves brain edema resulting from traumatic brain injury by suppressing the NF-κB/IL-1β signaling pathway and AQP4.Experimental and therapeutic medicine · 2020Article
- Inhibition of Aquaporin 4 Decreases Amyloid Aβ40 Drainage Around Cerebral Vessels.Molecular neurobiology · 2020Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Aquaporin-4 (AQP4), the principal water channel in astrocytes, is involved in brain water movement, inflammation, and neuroexcitation. In this study, there was strong neuroprotection in mice lacking AQP4 in a model of global cerebral ischemia produced by transient, bilateral carotid artery occlusion (BCAO). Survival and neurological outcome were greatly improved in the AQP4(-/-) vs. AQP4(+/+) mice after occlusion, with large and robust differences in both outbred (CD1) and inbred (C57bl/6) mouse strains without or with mechanical ventilation. Improved survival was also seen in mice lacking the scaffold protein α-syntrophin, which manifest reduced astrocyte water permeability secondary to defective AQP4 plasma membrane targeting. Intracranial pressure elevation and brain water accumulation were much reduced in the AQP4(-/-) vs. AQP4(+/+) mice after carotid artery occlusion, as were blood-brain barrier (BBB) disruption and neuronal loss. Brain slices from AQP4(-/-) mice showed significantly reduced cell swelling and cytotoxicity in response to oxygen-glucose deprivation, compared with slices from AQP4(+/+) mice. Our findings suggest that the neuroprotective effect of AQP4 deletion in global cerebral ischemia involves reduced astrocyte swelling and brain water accumulation, resulting in reduced BBB disruption, inflammation, and neuron death. AQP4 water transport inhibition may improve survival and neurological outcome after cardiac arrest and in other conditions associated with global cerebral ischemia.
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Registered trials
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