Targeted hsp70.1 disruption increases infarction volume after focal cerebral ischemia in mice.
OBJECTIVE
Heat-shock proteins (HSPs) are highly conserved proteins that are induced by a variety of stresses. HSP70 is a 70-kDa HSP family known to have cytoprotective effects against various insults. The role of HSP70 in cerebral ischemia remains to be elucidated in vivo.


METHODS
To investigate the effect of reduced HSP70 levels on cerebral ischemia, focal cerebral ischemia by intraluminal occlusion of the middle cerebral artery was induced in hsp70.1 knockout mice. The expressions of hsp70.1 and hsp70.3 mRNAs and HSP70 protein were determined, and infarction volumes were measured and compared.


RESULTS
Northern blots confirmed the absence of hsp70.1 mRNA expression in the knockout mice. The mean infarction volume was significantly larger in hsp70.1 knockout mice (92.5+/-8.3 mm(3)) than in the wild-type mice (59.3+/-8.9 mm,(3) P<0.001). Western blots showed increased HSP70 expression in the ischemic hemisphere in both knockout and wild-type mice, but HSP70 expression levels in knockout mice were significantly lower than those in their wild-type littermates. Immunohistochemistry did not show any significant differences between the knockout and wild-type animals and showed increased HSP70 immunoreactivity in the ischemic hemisphere, with predominance in the cerebral cortex, especially in the penumbra.


CONCLUSIONS
Our results suggest that hsp70.1 plays an important role in the early protection of the brain, at least after acute focal cerebral ischemia in mice.
Lee
S H
SH
Department of Neurology, Seoul National University, Seoul, Korea. bwyoon@snu.ac.kr
Kim
M
M
Yoon
B W
BW
Kim
Y J
YJ
Ma
S J
SJ
Roh
J K
JK
Lee
J S
JS
Seo
J S
JS
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D001923:Brain Chemistry; D002545:Brain Ischemia / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D002544:Cerebral Infarction / Q000209:etiology / Q000235:genetics* / Q000473:pathology*; D019610:Cytoprotection / Q000235:genetics; D004195:Disease Models, Animal; D018390:Gene Targeting; D018840:HSP70 Heat-Shock Proteins / Q000172:deficiency* / Q000235:genetics; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D015800:Protozoan Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis
D018840:HSP70 Heat-Shock Proteins; D015800:Protozoan Proteins; D012333:RNA, Messenger; C081884:heat-shock protein 70.1