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Cited by 315Ion Transport and Channel RegulationBarrier Structure and Function StudiesCerebrospinal fluid and hydrocephalus

Role of Aquaporin-4 in Cerebral Edema and Stroke

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Zador, Zsolt, Stiver, Shirley, Wang, Vincent, Manley, Geoffrey T.·2008·Handbook of Experimental Pharmacology
DOI 10.1007/978-3-540-79885-9_7PMC PMC3516842
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Abstract

Cerebral edema plays a central role in the pathophysiology of many diseases of the central nervous system (CNS) including ischemia, trauma, tumors, inflammation, and metabolic disturbances. The formation of cerebral edema results in an increase in tissue water content and brain swelling which, if unchecked, can lead to elevated intracranial pressure (ICP), reduced cerebral blood flow, and ultimately cerebral herniation and death. Despite the clinical significance of cerebral edema, the mechanism of brain water transport and edema formation remain poorly understood. As a result, current therapeutic tools for managing cerebral edema have changed little in the past 90 years. "Malignant ischemic stroke" is characterized by high mortality (80%) and represents a major clinical problem in cerebrovascular disease. Widespread ischemic injury in these patients causes progressive cerebral edema, increased ICP, and rapid clinical decline. In response to these observations, a series of recent studies have begun to target cerebral edema in the management of large ischemic strokes. During cerebral edema formation, the glial water channel aquaporin-4 (AQP4) has been show to facilitate astrocyte swelling ("cytotoxic swelling"). AQP4 has also been seen to be responsible for the reabsorption of extracellular edema fluid ("vasogenic edema"). In the present review, the role of AQP4 in the development of cerebral edema is discussed with emphasis on its contribution to ischemic edema. We also examine the potential of AQP4 as a therapeutic target in edema associated with stroke.

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  • Reactive astrocytes induced by ischemia promote CNS recovery and repair.

    “previous studies have provided evidence that reactive astrocytes induced by ischemia promote CNS recovery and repair1,10,11.”

    From Neurotoxic reactive astrocytes are induced by activated microglia (2017) · cites this paper as [11]

    Section 3.2 discusses ischemic edema and tissue damage, but does not say that reactive astrocytes promote recovery or repair. Searches for reactive astrocytes, recovery, repair, and glial scar formation found no passage making that claim; the glial-scar reference alone does not establish it. (LLM, conf=0.73)

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References 48 · Cited by 315

Research works printed but not linked: 48

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Authors
Zador, Z., Stiver, S., Wang, V., & Manley, G. T.
Affiliations
University of California, San Francisco (US)
Corresponding author
Manley, Geoffrey T.
ORCID
Venue
Handbook of Experimental Pharmacology
Publisher
Springer Berlin Heidelberg
Published
2008-12-18
Issue
190
Pages
159-170
ISSN
0171-2004 (ISSN-L)
DOI
10.1007/978-3-540-79885-9_7
PMC
PMC3516842
OpenAlex
W172954148
Cited by
315
References
48
Citations by year
2026: 7 · 2025: 15 · 2024: 15 · 2023: 14 · 2022: 23 · 2021: 28 · 2020: 14 · 2019: 16 · 2018: 14 · 2017: 16 · 2016: 22 · 2015: 18 · 2014: 24 · 2013: 20 · 2012: 23
FWCI
19.82
Type
book chapter
Language
en
Open access
Locations
  • Handbook of experimental pharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Research Explorer (The University of Manchester) (submittedVersion)
Funders
  • National Institutes of Health
  • University of California, San Francisco
  • National Institute of Neurological Disorders and Stroke (NIH NS050173, R01NS050173)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
Keywords
aquaporin-4, cerebral edema, ischemic stroke, astrocyte swelling, vasogenic edema, intracranial pressure, therapeutic target
MeSH terms
Animals, Brain Edema, Central Nervous System, Disease Models, Animal, Humans, Water, Water-Electrolyte Balance, Mice, Knockout, Stroke, Mice, Aquaporin 4

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