{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T15:15:18Z","timestamp":1783782918912,"version":"3.55.0"},"reference-count":76,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NIA","award":["9R44AG073096-02A1"],"award-info":[{"award-number":["9R44AG073096-02A1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>A primary purpose of sleep for humans is to remove toxins and metabolic wastes from the brain (e.g., A\u03b2, tau, lactate) that would otherwise build up and compromise brain functionality. There are currently no drugs or devices that have been clinically shown in humans to enhance brain toxin removal, either during sleep or wakefulness. This perspective article focuses on a recently (re)discovered major route of toxin drainage from the human brain through meningeal lymphatic vessels (mLVs) and the primary enhancer of their flow\u2014the cytokine Vascular Endothelial Growth Factor (VEGF). The purpose of this perspective article is to present pre-clinical and clinical evidence relevant to a new bioengineered technology (Transcranial Radiofrequency Treatment; TRFT) that appears to enhance mLV flow to increase brain toxin cleansing in humans during wakefulness. In being both safe and non-invasive, TRFT is administered in-home, presently through a device called \u201cMemorEM\u201d. Two months of daily TRFT during wakefulness increased the typically low plasma\/brain levels of VEGF in Alzheimer\u2019s Disease (AD) subjects, which was associated with increased A\u03b2 and tau toxin removal from their brains during wakefulness\u2014ostensibly through VEGF-increased mLV flow. Even irrespective of baseline VEGF levels, brain toxin cleansing was increased by TRFT in AD subjects, who also experienced a notable reversal of their cognitive impairment after TRFT. Additional clinical studies are nonetheless required to firmly establish TRFT\u2019s brain cleansing abilities during wakefulness. In performing a major duty of sleep, TRFT during wakefulness is proposed as a viable intervention to counter the decline in nighttime brain toxin cleansing that occurs with aging and in multiple brain diseases, most notably Alzheimer\u2019s Disease. The implications of TRFT for insomnia and for sleep deprivation are also discussed, as is the potential for TRFT to extend healthy human longevity.<\/jats:p>","DOI":"10.3390\/jcm14030926","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T04:05:47Z","timestamp":1738296347000},"page":"926","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Brain Toxin Cleansing of Sleep Achieved During Wakefulness"],"prefix":"10.3390","volume":"14","author":[{"given":"Gary W.","family":"Arendash","sequence":"first","affiliation":[{"name":"RF Longevity, 428 E. 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