{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:35:30Z","timestamp":1792031730223,"version":"4.4.0"},"reference-count":193,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2015,4,30]],"date-time":"2015-04-30T00:00:00Z","timestamp":1430352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Brain edema is a potentially fatal pathological state that occurs after brain injuries such as stroke and head trauma. In the edematous brain, excess accumulation of extracellular fluid results in elevation of intracranial pressure, leading to impaired nerve function. Despite the seriousness of brain edema, only symptomatic treatments to remove edema fluid are currently available. Thus, the development of novel anti-edema drugs is required. The pathogenesis of brain edema is classified as vasogenic or cytotoxic edema. Vasogenic edema is defined as extracellular accumulation of fluid resulting from disruption of the blood-brain barrier (BBB) and extravasations of serum proteins, while cytotoxic edema is characterized by cell swelling caused by intracellular accumulation of fluid. Various experimental animal models are often used to investigate mechanisms underlying brain edema. Many soluble factors and functional molecules have been confirmed to induce BBB disruption or cell swelling and drugs targeted to these factors are expected to have anti-edema effects. In this review, we discuss the mechanisms and involvement of factors that induce brain edema formation, and the possibility of anti-edema drugs targeting them.<\/jats:p>","DOI":"10.3390\/ijms16059949","type":"journal-article","created":{"date-parts":[[2015,4,30]],"date-time":"2015-04-30T08:58:53Z","timestamp":1430384333000},"page":"9949-9975","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":305,"title":["Pathogenesis of Brain Edema and Investigation into  Anti-Edema Drugs"],"prefix":"10.3390","volume":"16","author":[{"given":"Shotaro","family":"Michinaga","sequence":"first","affiliation":[{"name":"Laboratory of Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, Tonda-bayashi,  Osaka 584-8540, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Koyama","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, Tonda-bayashi,  Osaka 584-8540, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s00401-009-0541-0","article-title":"Pathology and new players in the pathogenesis of brain edema","volume":"118","author":"Nag","year":"2009","journal-title":"Acta Neuropathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.neuint.2013.01.015","article-title":"Brain edema in acute liver failure and chronic liver disease: Similarities and differences","volume":"62","author":"Bosoi","year":"2013","journal-title":"Neurochem. 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