ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2024
Long-term isoflurane anesthesia induces cognitive deficits via AQP4 depolarization mediated blunted glymphatic inflammatory proteins clearance.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Novel Therapeutic Insights Into Alzheimer's Disease: Glymphatic System and Meningeal Lymphatic Vessels.Aging cell · 2026Review
- Surgical and anesthetic rewiring of the glymphatic system in postoperative cognitive dysfunction.Neural regeneration research · 2026Article
- Impact of early glymphatic disorders on the development of vascular dementia.BMC medical imaging · 2026Article
- Transcranial magnetic stimulation mitigates perioperative neurocognitive disorders by regulating the function of the glymphatic system.Cell communication and signaling : CCS · 2026Article
- New Strategies for the Prevention and Therapy of Alzheimer's Disease Based on Stimulation of Brain Drainage and Lymphatic Clearance.International journal of molecular sciences · 2026Review
- Glymphatic-meningeal lymphatic system imbalance: a peripheral-to-central inflammatory bridge in perioperative neurocognitive disorders.Frontiers in immunology · 2026Review
- Risk Assessment of Serum Biomarkers with Perioperative Neurocognitive Dysfunction in Elderly Patients Undergoing Thoracic Surgery: A Prospective Cohort Study.Cellular and molecular neurobiology · 2025Article
- Insulin Resistance and Cognitive Function in Nondiabetic Patients With Cerebral Small Vessel Disease: Role of Brain Glymphatic Function.Brain and behavior · 2025Article
- Beyond apoptosis: Exploring necroptosis, ferroptosis, and pyroptosis in sevoflurane- and isoflurane-associated PNDs.IBRO neuroscience reports · 2025Review
- Clearance mechanisms of the glymphatic/lymphatic system in the brain: new therapeutic perspectives for cognitive impairment.Cognitive neurodynamics · 2025Review
- The Fluidic Connectome in Brain Disease: Integrating Aquaporin-4 Polarity with Multisystem Pathways in Neurodegeneration.International journal of molecular sciences · 2025Review
- Molecular and Clinical Considerations for Anesthesia in the Aging Brain.International journal of molecular sciences · 2025Review
- Glymphatic and meningeal lymphatic dysfunction in Alzheimer's disease: Mechanisms and therapeutic perspectives.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- The Relationship Between Glymphatic Function, White Matter Hyperintensity and Cognition: A Structural Equation Model MRI Study.CNS neuroscience & therapeutics · 2025Article
- Melatonin Regulates Glymphatic Function to Affect Cognitive Deficits, Behavioral Issues, and Blood-Brain Barrier Damage in Mice After Intracerebral Hemorrhage: Potential Links to Circadian Rhythms.CNS neuroscience & therapeutics · 2025Article
- Loss of aquaporin-4 impairs cerebrospinal fluid solute clearance through cerebrospinal fluid drainage pathways.Scientific reports · 2024Article
- Influencing factors of glymphatic system during perioperative period.Frontiers in neuroscience · 2024Review
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Perioperative neurocognitive disorders (PND) refer to cognitive deterioration that occurs after surgery or anesthesia. Prolonged isoflurane exposure has potential neurotoxicity and induces PND, but the mechanism is unclear. The glymphatic system clears harmful metabolic waste from the brain. This study sought to unveil the functions of glymphatic system in PND and explore the underlying molecular mechanisms. The PND mice model was established by long term isoflurane anesthesia. The glymphatic function was assessed by multiple in vitro and in vivo methods. An adeno-associated virus was used to overexpress AQP4 and TGN-020 was used to inhibit its function. This research revealed that the glymphatic system was impaired in PND mice and the blunted glymphatic transport was closely associated with the accumulation of inflammatory proteins in the hippocampus. Increasing AQP4 polarization could enhance glymphatic transport and suppresses neuroinflammation, thereby improve cognitive function in the PND model mice. However, a marked impaired glymphatic inflammatory proteins clearance and the more severe cognitive dysfunction were observed when decreasing AQP4 polarization. Therefore, long-term isoflurane anesthesia causes blunted glymphatic system by inducing AQP4 depolarization, enhanced the AQP4 polarization can alleviate the glymphatic system malfunction and reduce the neuroinflammatory response, which may be a potential treatment strategy for PND.
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