Differential cerebral protein synthesis and heat shock protein 70 expression in the core and penumbra of rat brain after transient focal ischemia.
OBJECTIVE
The purpose of this study was to correlate the cerebral protein synthesis (CPS) reductions in the ischemic core and penumbra with the metabolic stress response indicated by heat shock protein 70 (HSP70) synthesis.


METHODS
Rats were subjected to 90 minutes of temporary focal cerebral ischemia produced by occlusion of the middle cerebral artery, using the endovascular suture model. Regional CPS was qualitatively evaluated, with [(35)S]methionine autoradiography, after reperfusion for 2 to 72 hours. The observed changes were correlated with HSP70 immunoreactivity, as assessed in the same brain sections. The ischemic core in the striatum was characterized by HSP70 expression only in endothelial and/or glial cells, with an absence of expression in neurons. The penumbra was delineated as the cortical middle cerebral artery territory region in which HSP70 was also expressed in metabolically stressed neurons.


RESULTS
After 2 hours of reperfusion, CPS was reduced to 30 +/- 16% of the homologous contralateral hemisphere value in the core and to 75 +/- 22% in the penumbra (P < 0.05). This difference was still present at 72 hours, when CPS values were 62 +/- 21% and 98 +/- 29% of the nonischemic contralateral hemisphere values in the core and penumbra, respectively (P < 0.05).


CONCLUSIONS
Persistent inhibition of CPS in regions in which neuronal HSP70 expression is absent may distinguish core areas of infarction from penumbral regions in which neuronal HSP70 is present, which eventually recover from sublethal metabolic stress during reperfusion after temporary focal ischemia.
Kokubo
Yasuaki
Y
Department of Neurological Surgery, University of California, San Francisco, San Francisco, California 94143, USA.
Liu
Jialing
J
Rajdev
Sunita
S
Kayama
Takamasa
T
Sharp
Frank R
FR
Weinstein
Philip R
PR
D000818:Animals; D001345:Autoradiography; D002560:Cerebrovascular Circulation / Q000502:physiology; D004195:Disease Models, Animal; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis* / Q000096:biosynthesis*; D006439:Hemodynamics / Q000502:physiology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000000981:diagnostic imaging* / Q000209:etiology / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000096:biosynthesis*; D011237:Predictive Value of Tests; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013997:Time Factors
D018840:HSP70 Heat-Shock Proteins; D009419:Nerve Tissue Proteins