Role of Aquaporin-4 in Cerebral Edema and Stroke
TLDR
The role of AQP4 in the development of cerebral edema is discussed with emphasis on its contribution to ischemic edema, and the potential of AQp4 as a therapeutic target in edema associated with stroke is examined.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.read more
Citations
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References
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Journal ArticleDOI
Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke.
Geoffrey T. Manley,Miki Fujimura,Tonghui Ma,Nobuo Noshita,Ferda Filiz,Andrew W. Bollen,Pak H. Chan,Alan S. Verkman +7 more
TL;DR: It is shown that mice deficient in aquaporin-4 (AQP4), a glial membrane water channel, have much better survival than wild-type mice in a model of brain edema caused by acute water intoxication, and suggested that AQP4 inhibition may provide a new therapeutic option for reducingbrain edema in a wide variety of cerebral disorders.
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Specialized membrane domains for water transport in glial cells : high-resolution immunogold cytochemistry of aquaporin-4 in rat brain
Søren Nielsen,Erlend A. Nagelhus,Mahmood Amiry-Moghaddam,Charles W. Bourque,Peter Agre,Ole Petter Ottersen +5 more
TL;DR: The highly polarized AQP4 expression indicates that these cells are equipped with specific membrane domains that are specialized for water transport, thereby mediating the flow of water between glial cells and the cavities filled with CSF and the intravascular space.
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'Malignant' Middle Cerebral Artery Territory Infarction: Clinical Course and Prognostic Signs
TL;DR: The prognosis of complete middle cerebral artery territory stroke is very poor and can be estimated by early clinical and neuroradiological data within the first few hours after the onset of symptoms.
Journal ArticleDOI
Mechanisms of brain injury after intracerebral haemorrhage
TL;DR: The coagulation cascade, haemoglobin breakdown products, and inflammation all play a part in ICH-induced injury and could provide new therapeutic targets and new therapeutic interventions for this severe form of stroke.