Differential cerebral protein synthesis and heat shock protein 70 expression in the core and penumbra of rat brain after transient focal ischemia

Yasuaki Kokubo, Jialing Liu, Sunita Rajdev, Takamasa Kayama, Frank R Sharp, Philip R. Weinstein, R. Loch Macdonald, J. Paul Elliott, Warren R. Selman

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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 [35S] 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). CONCLUSION: 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.

Original languageEnglish (US)
Pages (from-to)186-191
Number of pages6
JournalNeurosurgery
Volume53
Issue number1
StatePublished - Jul 1 2003
Externally publishedYes

Fingerprint

HSP70 Heat-Shock Proteins
Ischemia
Brain
Reperfusion
Physiological Stress
Proteins
Neurons
Middle Cerebral Artery Infarction
Middle Cerebral Artery
Brain Ischemia
Autoradiography
Neuroglia
Methionine
Infarction
Sutures
Endothelial Cells

Keywords

  • Cerebral ischemia
  • Heat shock proteins
  • Ischemic penumbra
  • Protein synthesis

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

Cite this

Differential cerebral protein synthesis and heat shock protein 70 expression in the core and penumbra of rat brain after transient focal ischemia. / Kokubo, Yasuaki; Liu, Jialing; Rajdev, Sunita; Kayama, Takamasa; Sharp, Frank R; Weinstein, Philip R.; Macdonald, R. Loch; Elliott, J. Paul; Selman, Warren R.

In: Neurosurgery, Vol. 53, No. 1, 01.07.2003, p. 186-191.

Research output: Contribution to journalArticle

Kokubo, Y, Liu, J, Rajdev, S, Kayama, T, Sharp, FR, Weinstein, PR, Macdonald, RL, Elliott, JP & Selman, WR 2003, 'Differential cerebral protein synthesis and heat shock protein 70 expression in the core and penumbra of rat brain after transient focal ischemia', Neurosurgery, vol. 53, no. 1, pp. 186-191.
Kokubo, Yasuaki ; Liu, Jialing ; Rajdev, Sunita ; Kayama, Takamasa ; Sharp, Frank R ; Weinstein, Philip R. ; Macdonald, R. Loch ; Elliott, J. Paul ; Selman, Warren R. / Differential cerebral protein synthesis and heat shock protein 70 expression in the core and penumbra of rat brain after transient focal ischemia. In: Neurosurgery. 2003 ; Vol. 53, No. 1. pp. 186-191.
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abstract = "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 [35S] 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). CONCLUSION: 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.",
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AU - Kokubo, Yasuaki

AU - Liu, Jialing

AU - Rajdev, Sunita

AU - Kayama, Takamasa

AU - Sharp, Frank R

AU - Weinstein, Philip R.

AU - Macdonald, R. Loch

AU - Elliott, J. Paul

AU - Selman, Warren R.

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N2 - 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 [35S] 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). CONCLUSION: 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.

AB - 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 [35S] 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). CONCLUSION: 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.

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