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Oncotic Cell Death in Stroke

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

Abstract

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.

Keywords

Cerebral oedema Ion channels Oncosis Stroke 

Abbreviations

AMPA

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

AQP

Aquaporin

ASIC

Acid-sensing ion channels

ATP

Adenosine triphosphate

BBB

Blood-brain barrier

CCC

Chloride co-transporter

CNS

Central nervous system

CSF

Cerebrospinal fluid

GABAA

γ-Aminobutyric acid type A

iNOS

Inducible nitric oxide synthase

MCAO

Middle cerebral artery occlusion

NBCe1

Na+/HCO3 co-transporter 1

NHE

Na+/H+ exchanger

NKCC1

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

NMDA

N-methyl-d-aspartate

PI

Propidium iodide

ROS

Reactive oxygen species

SUR1

Sulfonylurea receptor isoform 1

TNF-α

Tumour necrosis factor alpha

TRP

Transient receptor potential

UCP

Uncoupling protein

Notes

Acknowledgements

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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