Evidence that the EphA2 receptor exacerbates ischemic brain injury

Thundyil, John, Manzanero, Silvia, Pavlovski, Dale, Cully, Tanya R., Lok, Ker-Zhing, Widiapradja, Alexander, Chunduri, Prasad, Jo, Dong-Gyu, Naruse, Chie, Asano, Masahide, Launikonis, Bradley S., Sobey, Christopher G., Coulthard, Mark G. and Arumugam, Thiruma V. (2013) Evidence that the EphA2 receptor exacerbates ischemic brain injury. PLoS One, 8 1: e53528.1-e53528.8. doi:10.1371/journal.pone.0053528

Author Thundyil, John
Manzanero, Silvia
Pavlovski, Dale
Cully, Tanya R.
Lok, Ker-Zhing
Widiapradja, Alexander
Chunduri, Prasad
Jo, Dong-Gyu
Naruse, Chie
Asano, Masahide
Launikonis, Bradley S.
Sobey, Christopher G.
Coulthard, Mark G.
Arumugam, Thiruma V.
Title Evidence that the EphA2 receptor exacerbates ischemic brain injury
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-01-07
Sub-type Article (original research)
DOI 10.1371/journal.pone.0053528
Open Access Status DOI
Volume 8
Issue 1
Start page e53528.1
End page e53528.8
Total pages 8
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2014
Language eng
Formatted abstract
Ephrin (Eph) signaling within the central nervous system is known to modulate axon guidance, synaptic plasticity, and to promote long-term potentiation. We investigated the potential involvement of EphA2 receptors in ischemic stroke-induced brain inflammation in a mouse model of focal stroke. Cerebral ischemia was induced in male C57Bl6/J wild-type (WT) and EphA2-deficient (EphA2−/−) mice by middle cerebral artery occlusion (MCAO; 60 min), followed by reperfusion (24 or 72 h). Brain infarction was measured using triphenyltetrazolium chloride staining. Neurological deficit scores and brain infarct volumes were significantly less in EphA2−/− mice compared with WT controls. This protection by EphA2 deletion was associated with a comparative decrease in brain edema, blood-brain barrier damage, MMP-9 expression and leukocyte infiltration, and higher expression levels of the tight junction protein, zona occludens-1. Moreover, EphA2−/− brains had significantly lower levels of the pro-apoptotic proteins, cleaved caspase-3 and BAX, and higher levels of the anti-apoptotic protein, Bcl-2 as compared to WT group. We confirmed that isolated WT cortical neurons express the EphA2 receptor and its ligands (ephrin-A1–A3). Furthermore, expression of all four proteins was increased in WT primary cortical neurons following 24 h of glucose deprivation, and in the brains of WT mice following stroke. Glucose deprivation induced less cell death in primary neurons from EphA2−/− compared with WT mice. In conclusion, our data provide the first evidence that the EphA2 receptor directly contributes to blood-brain barrier damage and neuronal death following ischemic stroke.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 8 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 10 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 08 Jan 2013, 10:44:35 EST by Dr Thiruma V Arumugam on behalf of School of Biomedical Sciences