Changes of polyamine metabolism and delayed neuronal degeneration of hippocampus after transient cerebral ischemia in Mongolian gerbils

Kyung-Ho Shin, H. J. Shin, Y. J. Lee, H. G. Kim, Sang-Hyun Choi, Y. S. Chun, B. G. Chun

Research output: Contribution to journalArticle

Abstract

Male Mongolian gerbils (60-80 g) were given DL-difluoromethylornithine (DFMO; 250 mg/kg, ip) and methylglyoxal bis(guanylhydrazone) (MGBG; 50 mg/k, ip), respectively, 1 h prior to transient (7 min) occlusion of bilateral common carotid arteries (OBC7) and a daily dose of one of them for 6 days after recirculation, and the polyamine contents, activities of ornithine and S-adenosylmethionine decarboxylases (ODC and SAM-DC), and light microscopic findings of the hippocampus were evaluated. The hippocampal putrescine (PT) levels of the control gerbils treated with saline (STGr), markedly increased after OBC7, showing a peak level at 24 h after recirculation. The peak PT level was reduced in DFMO treated gerbils (DTGr) and in MGBG treated gerbils (MTGr). And 7 days after recirculation, the PT level of DTGr was decreased to about 75% of the PT level in the sham operated group (nonTGr) and to about 55% of the STGr level, respectively. The hippocampal spermidine (SD) level of STGr tended to decline, showing the lowest value at 8 h after recirculation. But the spermidine (SD) level of DTGr was somewhat higher at 8 h after OBC7 than those of STGr and MTGr. The hippocampal spermine (SM) levels of all the experimental groups were little changed for 7 days after OBC. OBC7 markedly increased the hippocampal ODC activity, reaching a maximum (about 3 times higher than preischemic level) at 8 h and rapidly recovered to the control value by 24 h in STGr gerbils, and the OBC7-induced increase of ODC activity was significantly attenuated by DFMO or MGBG treatment. Whereas OBC7 induced a rapid decrease of the hippocampal SAM-DC activity follwed by gradual recovery to the preischemic level, and the decrease of the SAM-DC activity was slightly attenuated by DFMO or MGBG treatment. 7 Days after OBC7 the histological finding of the hippocampal complex stained with cresyl violet showed an extensive delayed neuronal damage in the CA1 region and to a lesser extent, in the dentate gyrus, sparing the CA3 region. And the neuronal death was aggravated by DFMO but significantly attenuated by MGBG. The immunochemical reactivity of hippocampus to anti-GFAP antibody was significantly increased in the CA1 region and to a lesser extent, in the dentate gyrus 7 days after OBC7, but was little changed in the CA3. And the increase of the anti-GFAP immunoreactivity was moderately enhanced by DFMO and significantly suppressed by MGBG. These results suggest that the polyamine metabolism may play a modulatory role in the ischemic brain damage.

Original languageEnglish
Pages (from-to)323-334
Number of pages12
JournalKorean Journal of Pharmacology
Volume32
Issue number3
Publication statusPublished - 1996 Dec 1

Fingerprint

Mitoguazone
Gerbillinae
Transient Ischemic Attack
Polyamines
Hippocampus
Putrescine
Spermidine
Dentate Gyrus
Adenosylmethionine Decarboxylase
Eflornithine
Ornithine
Spermine
Common Carotid Artery
Anti-Idiotypic Antibodies
Light

Keywords

  • brain ischema
  • delayed neuronal death
  • DFMO
  • hippocampus
  • MGBG
  • polyamines

ASJC Scopus subject areas

  • Pharmacology

Cite this

Changes of polyamine metabolism and delayed neuronal degeneration of hippocampus after transient cerebral ischemia in Mongolian gerbils. / Shin, Kyung-Ho; Shin, H. J.; Lee, Y. J.; Kim, H. G.; Choi, Sang-Hyun; Chun, Y. S.; Chun, B. G.

In: Korean Journal of Pharmacology, Vol. 32, No. 3, 01.12.1996, p. 323-334.

Research output: Contribution to journalArticle

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AU - Shin, Kyung-Ho

AU - Shin, H. J.

AU - Lee, Y. J.

AU - Kim, H. G.

AU - Choi, Sang-Hyun

AU - Chun, Y. S.

AU - Chun, B. G.

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N2 - Male Mongolian gerbils (60-80 g) were given DL-difluoromethylornithine (DFMO; 250 mg/kg, ip) and methylglyoxal bis(guanylhydrazone) (MGBG; 50 mg/k, ip), respectively, 1 h prior to transient (7 min) occlusion of bilateral common carotid arteries (OBC7) and a daily dose of one of them for 6 days after recirculation, and the polyamine contents, activities of ornithine and S-adenosylmethionine decarboxylases (ODC and SAM-DC), and light microscopic findings of the hippocampus were evaluated. The hippocampal putrescine (PT) levels of the control gerbils treated with saline (STGr), markedly increased after OBC7, showing a peak level at 24 h after recirculation. The peak PT level was reduced in DFMO treated gerbils (DTGr) and in MGBG treated gerbils (MTGr). And 7 days after recirculation, the PT level of DTGr was decreased to about 75% of the PT level in the sham operated group (nonTGr) and to about 55% of the STGr level, respectively. The hippocampal spermidine (SD) level of STGr tended to decline, showing the lowest value at 8 h after recirculation. But the spermidine (SD) level of DTGr was somewhat higher at 8 h after OBC7 than those of STGr and MTGr. The hippocampal spermine (SM) levels of all the experimental groups were little changed for 7 days after OBC. OBC7 markedly increased the hippocampal ODC activity, reaching a maximum (about 3 times higher than preischemic level) at 8 h and rapidly recovered to the control value by 24 h in STGr gerbils, and the OBC7-induced increase of ODC activity was significantly attenuated by DFMO or MGBG treatment. Whereas OBC7 induced a rapid decrease of the hippocampal SAM-DC activity follwed by gradual recovery to the preischemic level, and the decrease of the SAM-DC activity was slightly attenuated by DFMO or MGBG treatment. 7 Days after OBC7 the histological finding of the hippocampal complex stained with cresyl violet showed an extensive delayed neuronal damage in the CA1 region and to a lesser extent, in the dentate gyrus, sparing the CA3 region. And the neuronal death was aggravated by DFMO but significantly attenuated by MGBG. The immunochemical reactivity of hippocampus to anti-GFAP antibody was significantly increased in the CA1 region and to a lesser extent, in the dentate gyrus 7 days after OBC7, but was little changed in the CA3. And the increase of the anti-GFAP immunoreactivity was moderately enhanced by DFMO and significantly suppressed by MGBG. These results suggest that the polyamine metabolism may play a modulatory role in the ischemic brain damage.

AB - Male Mongolian gerbils (60-80 g) were given DL-difluoromethylornithine (DFMO; 250 mg/kg, ip) and methylglyoxal bis(guanylhydrazone) (MGBG; 50 mg/k, ip), respectively, 1 h prior to transient (7 min) occlusion of bilateral common carotid arteries (OBC7) and a daily dose of one of them for 6 days after recirculation, and the polyamine contents, activities of ornithine and S-adenosylmethionine decarboxylases (ODC and SAM-DC), and light microscopic findings of the hippocampus were evaluated. The hippocampal putrescine (PT) levels of the control gerbils treated with saline (STGr), markedly increased after OBC7, showing a peak level at 24 h after recirculation. The peak PT level was reduced in DFMO treated gerbils (DTGr) and in MGBG treated gerbils (MTGr). And 7 days after recirculation, the PT level of DTGr was decreased to about 75% of the PT level in the sham operated group (nonTGr) and to about 55% of the STGr level, respectively. The hippocampal spermidine (SD) level of STGr tended to decline, showing the lowest value at 8 h after recirculation. But the spermidine (SD) level of DTGr was somewhat higher at 8 h after OBC7 than those of STGr and MTGr. The hippocampal spermine (SM) levels of all the experimental groups were little changed for 7 days after OBC. OBC7 markedly increased the hippocampal ODC activity, reaching a maximum (about 3 times higher than preischemic level) at 8 h and rapidly recovered to the control value by 24 h in STGr gerbils, and the OBC7-induced increase of ODC activity was significantly attenuated by DFMO or MGBG treatment. Whereas OBC7 induced a rapid decrease of the hippocampal SAM-DC activity follwed by gradual recovery to the preischemic level, and the decrease of the SAM-DC activity was slightly attenuated by DFMO or MGBG treatment. 7 Days after OBC7 the histological finding of the hippocampal complex stained with cresyl violet showed an extensive delayed neuronal damage in the CA1 region and to a lesser extent, in the dentate gyrus, sparing the CA3 region. And the neuronal death was aggravated by DFMO but significantly attenuated by MGBG. The immunochemical reactivity of hippocampus to anti-GFAP antibody was significantly increased in the CA1 region and to a lesser extent, in the dentate gyrus 7 days after OBC7, but was little changed in the CA3. And the increase of the anti-GFAP immunoreactivity was moderately enhanced by DFMO and significantly suppressed by MGBG. These results suggest that the polyamine metabolism may play a modulatory role in the ischemic brain damage.

KW - brain ischema

KW - delayed neuronal death

KW - DFMO

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KW - MGBG

KW - polyamines

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