Prolonged expression of hsp70 mRNA following transient focal cerebral ischemia in transgenic mice overexpressing CuZn-superoxide dismutase

Hideyuki Kamii, Hiroyuki Kinouchi, Frank R Sharp, Jari Koistinaho, Charles J. Epstein, Pak H. Chan

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

The distribution of heat shock protein hsp70 mRNA after 10 min of middle cerebral artery (MCA) occlusion was investigated through in situ hybridization in transgenic (Tg) mice overexpressing CuZn-superoxide dismutase (CuZn-SOD) and in control nontransgenic (nTg) littermates. In the ischemic cortex of nTg mice, hsp70 mRNA was detected 1 h after reperfusion and was observed for up to 6 h. In Tg mice, however, it was still detectable within the cortex even at 24 h. In the caudate putamen, hsp70 mRNA appeared at 1 h and was present for up to 6 h in both nTg and Tg mice. Although hsp70 mRNA was detected in the thalamus only at 1 h in nTg mice, it was observed for up to 6 h in Tg mice. Similarly, hsp70 mRNA was detected in the hippocampus of nTg mice only at 1 h, whereas it was detected in Tg mice at 1 h and continued up to 24 h, with high intensity in the CA1 subfield. Despite the significant amounts of hsp70 mRNA in both Tg and nTg mice following ischemia, there was no observable neuronal necrosis (as assessed using hematoxylin and eosin staining) for up to 7 days. Cortical cerebral blood flow (CBF), measured by laser-Doppler flowmetry, did not differ between nTg and Tg mice during ischemia and reperfusion, despite exhibiting hyperemia following hypoperfusion. These results suggest that oxidative stress affects the expression of hsp70 following temporary focal ischemia. An alteration in oxidative stress, which resulted from reduced levels of superoxide radicals in the presence of the CuZn-SOD transgenes, may permit the prolonged expression of hsp70. This prolonged expression of hsp70 mRNA in cortex cannot be accounted for by changes of CBF in Tg mice during ischemia and reperfusion.

Original languageEnglish (US)
Pages (from-to)478-486
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Volume14
Issue number3
StatePublished - May 1994
Externally publishedYes

Fingerprint

Transient Ischemic Attack
Transgenic Mice
Superoxide Dismutase
Messenger RNA
Cerebrovascular Circulation
Ischemia
Reperfusion
Oxidative Stress
Laser-Doppler Flowmetry
Middle Cerebral Artery Infarction
Putamen
Hyperemia
Hematoxylin
Eosine Yellowish-(YS)
Heat-Shock Proteins
Thalamus
Transgenes
Superoxides
In Situ Hybridization
Hippocampus

Keywords

  • Focal brain ischemia
  • Heat shock protein
  • hsp70 mRNA
  • Oxygen free- radicals
  • Superoxide dismutase
  • Transgenic mouse

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

Cite this

Prolonged expression of hsp70 mRNA following transient focal cerebral ischemia in transgenic mice overexpressing CuZn-superoxide dismutase. / Kamii, Hideyuki; Kinouchi, Hiroyuki; Sharp, Frank R; Koistinaho, Jari; Epstein, Charles J.; Chan, Pak H.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 14, No. 3, 05.1994, p. 478-486.

Research output: Contribution to journalArticle

Kamii, Hideyuki ; Kinouchi, Hiroyuki ; Sharp, Frank R ; Koistinaho, Jari ; Epstein, Charles J. ; Chan, Pak H. / Prolonged expression of hsp70 mRNA following transient focal cerebral ischemia in transgenic mice overexpressing CuZn-superoxide dismutase. In: Journal of Cerebral Blood Flow and Metabolism. 1994 ; Vol. 14, No. 3. pp. 478-486.
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abstract = "The distribution of heat shock protein hsp70 mRNA after 10 min of middle cerebral artery (MCA) occlusion was investigated through in situ hybridization in transgenic (Tg) mice overexpressing CuZn-superoxide dismutase (CuZn-SOD) and in control nontransgenic (nTg) littermates. In the ischemic cortex of nTg mice, hsp70 mRNA was detected 1 h after reperfusion and was observed for up to 6 h. In Tg mice, however, it was still detectable within the cortex even at 24 h. In the caudate putamen, hsp70 mRNA appeared at 1 h and was present for up to 6 h in both nTg and Tg mice. Although hsp70 mRNA was detected in the thalamus only at 1 h in nTg mice, it was observed for up to 6 h in Tg mice. Similarly, hsp70 mRNA was detected in the hippocampus of nTg mice only at 1 h, whereas it was detected in Tg mice at 1 h and continued up to 24 h, with high intensity in the CA1 subfield. Despite the significant amounts of hsp70 mRNA in both Tg and nTg mice following ischemia, there was no observable neuronal necrosis (as assessed using hematoxylin and eosin staining) for up to 7 days. Cortical cerebral blood flow (CBF), measured by laser-Doppler flowmetry, did not differ between nTg and Tg mice during ischemia and reperfusion, despite exhibiting hyperemia following hypoperfusion. These results suggest that oxidative stress affects the expression of hsp70 following temporary focal ischemia. An alteration in oxidative stress, which resulted from reduced levels of superoxide radicals in the presence of the CuZn-SOD transgenes, may permit the prolonged expression of hsp70. This prolonged expression of hsp70 mRNA in cortex cannot be accounted for by changes of CBF in Tg mice during ischemia and reperfusion.",
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AB - The distribution of heat shock protein hsp70 mRNA after 10 min of middle cerebral artery (MCA) occlusion was investigated through in situ hybridization in transgenic (Tg) mice overexpressing CuZn-superoxide dismutase (CuZn-SOD) and in control nontransgenic (nTg) littermates. In the ischemic cortex of nTg mice, hsp70 mRNA was detected 1 h after reperfusion and was observed for up to 6 h. In Tg mice, however, it was still detectable within the cortex even at 24 h. In the caudate putamen, hsp70 mRNA appeared at 1 h and was present for up to 6 h in both nTg and Tg mice. Although hsp70 mRNA was detected in the thalamus only at 1 h in nTg mice, it was observed for up to 6 h in Tg mice. Similarly, hsp70 mRNA was detected in the hippocampus of nTg mice only at 1 h, whereas it was detected in Tg mice at 1 h and continued up to 24 h, with high intensity in the CA1 subfield. Despite the significant amounts of hsp70 mRNA in both Tg and nTg mice following ischemia, there was no observable neuronal necrosis (as assessed using hematoxylin and eosin staining) for up to 7 days. Cortical cerebral blood flow (CBF), measured by laser-Doppler flowmetry, did not differ between nTg and Tg mice during ischemia and reperfusion, despite exhibiting hyperemia following hypoperfusion. These results suggest that oxidative stress affects the expression of hsp70 following temporary focal ischemia. An alteration in oxidative stress, which resulted from reduced levels of superoxide radicals in the presence of the CuZn-SOD transgenes, may permit the prolonged expression of hsp70. This prolonged expression of hsp70 mRNA in cortex cannot be accounted for by changes of CBF in Tg mice during ischemia and reperfusion.

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