Hypothermia Identifies Dynamin as a Potential Therapeutic Target in Experimental Stroke

Jong Youl Kim, Nuri Kim, Jongeun Lee, Midori A. Yenari

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Apoptosis is a cell death pathway that is activated in ischemic stroke. The interaction between Fas and its ligand (FasL) initiates a complex pattern of intracellular events involving the recruitment of specific adaptor proteins and the development of apoptosis. We recently reported that dynamin is increased after experimental stroke, and its inhibition improves neurological outcome. Dynamin has been shown to transport Fas from the endoplasmic reticulum to the cell surface where it can be bound by its ligand, FasL. Hypothermia has been shown to improve outcome in numerous stroke models, and this protection is associated with reduced apoptosis and Fas expression. To explore the contribution of dynamin to hypothermic neuroprotection, we subjected mice to distal middle cerebral artery occlusion (dMCAO) and applied one of two cooling paradigms: one where cooling began at the onset of dMCAO (early hypothermia) and another where cooling began 1 hour later (delayed hypothermia), compared with normothermia (Norm). Both cooling paradigms reduced numbers of apoptotic cells, as well as Fas and dynamin compared with Norm. Fas and dynamin were co-expressed in neurons. Neuronal cultures were exposed to oxygen glucose deprivation. Hypothermia decreased dynamin as well as surface expression of Fas, and this correlated to reduced cell death. The results of this study suggest that dynamin may participate in the Fas-mediated apoptotic pathway, and its reduction may be linked to hypothermic neuroprotection.

Original languageEnglish
Pages (from-to)171-177
Number of pages7
JournalTherapeutic hypothermia and temperature management
Volume7
Issue number3
DOIs
Publication statusPublished - 2017 Sep 1

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Dynamins
Hypothermia
Stroke
Fas Ligand Protein
Middle Cerebral Artery Infarction
Apoptosis
Therapeutics
Cell Death
Endoplasmic Reticulum
Cell Count
Oxygen
Ligands
Neurons
Glucose

All Science Journal Classification (ASJC) codes

  • Critical Care and Intensive Care Medicine
  • Anesthesiology and Pain Medicine

Cite this

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abstract = "Apoptosis is a cell death pathway that is activated in ischemic stroke. The interaction between Fas and its ligand (FasL) initiates a complex pattern of intracellular events involving the recruitment of specific adaptor proteins and the development of apoptosis. We recently reported that dynamin is increased after experimental stroke, and its inhibition improves neurological outcome. Dynamin has been shown to transport Fas from the endoplasmic reticulum to the cell surface where it can be bound by its ligand, FasL. Hypothermia has been shown to improve outcome in numerous stroke models, and this protection is associated with reduced apoptosis and Fas expression. To explore the contribution of dynamin to hypothermic neuroprotection, we subjected mice to distal middle cerebral artery occlusion (dMCAO) and applied one of two cooling paradigms: one where cooling began at the onset of dMCAO (early hypothermia) and another where cooling began 1 hour later (delayed hypothermia), compared with normothermia (Norm). Both cooling paradigms reduced numbers of apoptotic cells, as well as Fas and dynamin compared with Norm. Fas and dynamin were co-expressed in neurons. Neuronal cultures were exposed to oxygen glucose deprivation. Hypothermia decreased dynamin as well as surface expression of Fas, and this correlated to reduced cell death. The results of this study suggest that dynamin may participate in the Fas-mediated apoptotic pathway, and its reduction may be linked to hypothermic neuroprotection.",
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Hypothermia Identifies Dynamin as a Potential Therapeutic Target in Experimental Stroke. / Kim, Jong Youl; Kim, Nuri; Lee, Jongeun; Yenari, Midori A.

In: Therapeutic hypothermia and temperature management, Vol. 7, No. 3, 01.09.2017, p. 171-177.

Research output: Contribution to journalArticle

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