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Cofilin-actin rod formation in experimental stroke is attenuated by therapeutic hypothermia and overexpression of the inducible 70 kD inducible heat shock protein (Hsp70)

Authors
 Kota Kurisu  ;  Jesung You  ;  Zhen Zheng  ;  Seok Joon Won  ;  Raymond A Swanson  ;  Midori A Yenari 
Citation
 BRAIN CIRCULATION, Vol.5(4) : 225-233, 2019-12 
Journal Title
BRAIN CIRCULATION
ISSN
 2394-8108 
Issue Date
2019-12
Keywords
Cofilin-actin rod ; heat shock protein 70 ; hypothermia ; neuroprotection ; stroke
Abstract
Background and purpose: Cofilin-actin rods are covalently linked aggregates of cofilin-1 and actin. Under ischemic conditions, these rods have been observed in neuronal dendrites and axons and may contribute to the loss of these processes. Hypothermia (Hypo) and the 70 kD inducible heat shock protein (Hsp70) are both known to improve outcomes after stroke, but the mechanisms are uncertain. Here, we evaluated the effect of these factors on cofilin-actin rod formation in a mouse model of stroke.

Materials and methods: Mice were subjected to distal middle cerebral artery occlusion (dMCAO) and treated with Hypo using a paradigm previously shown to be neuroprotective. We similarly studied mice that overexpressed transgenic (Tg) or were deficient knockout (Ko) in the inducible 70 kDa heat shock protein (Hsp70), also previously shown to be protective by our group and others. Cofilin-actin rod formation was assessed by histological analysis at 4 and 24 h after dMCAO. Its expression was analyzed in three different regions, namely, infarct core (the center of the infarct), middle cerebral artery (MCA) borderzone (the edge of the brain regions supplied by the MCA), and the ischemic borderzone (border of ischemic lesion). Ischemic lesion size and neurological deficits were also assessed.

Results: Both Hypo-treated and Hsp70 Tg mice had smaller lesion sizes and improved neurological outcomes, whereas Hsp70 Ko mice had larger lesion sizes and worsened neurological outcomes. Cofilin-actin rods were increased after stroke, but were reduced by therapeutic Hypo and in Hsp70 Tg mice. In contrast, cofilin-actin rods were increased in ischemic brains of Hsp70 Ko mice.

Conclusions: Cofilin-actin rod formation was suppressed under the conditions of neuroprotection and increased under circumstances where outcome was worsened. This suggests that cofilin-actin rods may act to participate in or exacerbate ischemic pathology and warrants further study as a potential therapeutic target.
Files in This Item:
T201906626.pdf Download
DOI
10.4103/bc.bc_52_19
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Emergency Medicine (응급의학교실) > 1. Journal Papers
Yonsei Authors
You, Je Sung(유제성) ORCID logo https://orcid.org/0000-0002-2074-6745
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/180627
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