Oncotic Cell Death in Stroke

  • Kep Yong Loh
  • Ziting Wang
  • Ping LiaoEmail author
Part of the Reviews of Physiology, Biochemistry and Pharmacology book series (REVIEWS, volume 176)


Oncotic cell death or oncosis represents a major mechanism of cell death in ischaemic stroke, occurring in many central nervous system (CNS) cell types including neurons, glia and vascular endothelial cells. In stroke, energy depletion causes ionic pump failure and disrupts ionic homeostasis. Imbalance between the influx of Na+ and Cl ions and the efflux of K+ ions through various channel proteins and transporters creates a transmembrane osmotic gradient, with ensuing movement of water into the cells, resulting in cell swelling and oncosis. Oncosis is a key mediator of cerebral oedema in ischaemic stroke, contributing directly through cytotoxic oedema, and indirectly through vasogenic oedema by causing vascular endothelial cell death and disruption of the blood-brain barrier (BBB). Hence, inhibition of uncontrolled ionic flux represents a novel and powerful strategy in achieving neuroprotection in stroke. In this review, we provide an overview of oncotic cell death in the pathology of stroke. Importantly, we summarised the therapeutically significant pathways of water, Na+, Cl and K+ movement across cell membranes in the CNS and their respective roles in the pathobiology of stroke.


Cerebral oedema Ion channels Oncosis Stroke 



α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid




Acid-sensing ion channels


Adenosine triphosphate


Blood-brain barrier


Chloride co-transporter


Central nervous system


Cerebrospinal fluid


γ-Aminobutyric acid type A


Inducible nitric oxide synthase


Middle cerebral artery occlusion


Na+/HCO3 co-transporter 1


Na+/H+ exchanger


Na+-K+-2Cl co-transporter 1




Propidium iodide


Reactive oxygen species


Sulfonylurea receptor isoform 1


Tumour necrosis factor alpha


Transient receptor potential


Uncoupling protein



This work was supported by grant NMRC/CIRG/1425/2015 and NMRC/CIRG/1469/2017 from the Singapore Ministry of Health’s National Medical Research Council to P.L.


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Duke-NUS Medical SchoolSingaporeSingapore
  2. 2.Calcium Signalling LaboratoryNational Neuroscience InstituteSingaporeSingapore
  3. 3.Department of UrologyNational University HospitalSingaporeSingapore
  4. 4.Singapore Institute of TechnologySingaporeSingapore

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