Delayed neuronal death after global incomplete ischemia in dogs is accompanied by changes in phospholipase C protein expression

Frederick Sieber, Richard J. Traystman, Lee J Martin

Research output: Contribution to journalArticle

Abstract

Activation of phospholipase C (PLC) increases intracellular Ca++ and may play a role in delayed neuronal death after ischemia. Because changes in intracellular Ca++ are believed to participate in ischemic neuronal injury, we tested the hypothesis that PLCβ protein levels are temporally altered in brain regions that undergo neurodegeneration after global in complete ischemia. Dogs (n = 12) were subjected to 20 minutes of global incomplete ischemia followed by recovery of either 1 (n = 5) or 7 days (n = 7). Six sham-operated animals were used as nonischemic controls. In hematoxylin and eosinstained brian sections, neuronal density at 1 day after ischemia was unchanged relative to nonischemic controls in hippocampus CA1, caudate and cerebellar cortex (anterior lobule). How ever, at 7 days after ischemia, neuronal densities were decreased to 56 ± 15% (mean ± SD) and 75 ± 17% of control in CA1 and caudate, respectively. At 1 and 7 days after ischemia the percentage of neurons showing ischemic injury increased from 13 ± 10 to 40 ± 35% in CA1, 24 ± 25 to 59 ± 16% in cerebellum and 4 ± 2 to 18 ± 12% in caudate. Densitometric analysis of immunocytochemically stained brain sections from controls (n = 3). 1 day after ischemia (n = 3) and 7 days after ischemia (n = 5) revealed that PLCβ immunoreactivity was increased in cerebellum at 1 day (0.274 ± 0.013 ν 0.295 ± 0.005 optical density units [OD] in control and 1 day, respectively) and 7 days (0.108 ± 0.009 ν 0.116 ± 0.005 OD in control and 7 days, respectively). PLCβ immunoreactivity was unchanged after ischemia in caudate and hippocampus. Western blot analysis of PLCβ immunoreactivity in the cerebellar cortex and hippocampus in the control (n = 3). 1 day (n = 2) and 7 days after ischemia (n = 2) groups showed that PLCβ levels were increased after ischemia in cerebellum 266% and 227% above control at 1 and 7 days, respectively. However in hippocampus. PLC expression after ischemia was unchanged at 97% and 84% of control at 1 and days, respectively. These results show that delayed neuronal degeneration after global incomplete ischemia is accompanied by regional abnormalities in PLC levels. Elevated PLC levels early may represent an aberrant signal transduction mechanism resulting in delayed cell damage, whereas decreased PLC levels later after ischemia may reflect ongoing neurodegeneration.

Original languageEnglish (US)
Pages (from-to)527-533
Number of pages7
JournalJournal of Cerebral Blood Flow and Metabolism
Volume17
Issue number5
StatePublished - May 1997

Fingerprint

Type C Phospholipases
Ischemia
Dogs
Proteins
Hippocampus
Cerebellum
Cerebellar Cortex
Wounds and Injuries
Brain
Hematoxylin
Signal Transduction
Western Blotting

Keywords

  • CA1
  • intracellular Ca homeostasis
  • ischemic neurodegeneration
  • signal transdiction

ASJC Scopus subject areas

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

Cite this

@article{911ab26ca9ac47b68778f752cba56d31,
title = "Delayed neuronal death after global incomplete ischemia in dogs is accompanied by changes in phospholipase C protein expression",
abstract = "Activation of phospholipase C (PLC) increases intracellular Ca++ and may play a role in delayed neuronal death after ischemia. Because changes in intracellular Ca++ are believed to participate in ischemic neuronal injury, we tested the hypothesis that PLCβ protein levels are temporally altered in brain regions that undergo neurodegeneration after global in complete ischemia. Dogs (n = 12) were subjected to 20 minutes of global incomplete ischemia followed by recovery of either 1 (n = 5) or 7 days (n = 7). Six sham-operated animals were used as nonischemic controls. In hematoxylin and eosinstained brian sections, neuronal density at 1 day after ischemia was unchanged relative to nonischemic controls in hippocampus CA1, caudate and cerebellar cortex (anterior lobule). How ever, at 7 days after ischemia, neuronal densities were decreased to 56 ± 15{\%} (mean ± SD) and 75 ± 17{\%} of control in CA1 and caudate, respectively. At 1 and 7 days after ischemia the percentage of neurons showing ischemic injury increased from 13 ± 10 to 40 ± 35{\%} in CA1, 24 ± 25 to 59 ± 16{\%} in cerebellum and 4 ± 2 to 18 ± 12{\%} in caudate. Densitometric analysis of immunocytochemically stained brain sections from controls (n = 3). 1 day after ischemia (n = 3) and 7 days after ischemia (n = 5) revealed that PLCβ immunoreactivity was increased in cerebellum at 1 day (0.274 ± 0.013 ν 0.295 ± 0.005 optical density units [OD] in control and 1 day, respectively) and 7 days (0.108 ± 0.009 ν 0.116 ± 0.005 OD in control and 7 days, respectively). PLCβ immunoreactivity was unchanged after ischemia in caudate and hippocampus. Western blot analysis of PLCβ immunoreactivity in the cerebellar cortex and hippocampus in the control (n = 3). 1 day (n = 2) and 7 days after ischemia (n = 2) groups showed that PLCβ levels were increased after ischemia in cerebellum 266{\%} and 227{\%} above control at 1 and 7 days, respectively. However in hippocampus. PLC expression after ischemia was unchanged at 97{\%} and 84{\%} of control at 1 and days, respectively. These results show that delayed neuronal degeneration after global incomplete ischemia is accompanied by regional abnormalities in PLC levels. Elevated PLC levels early may represent an aberrant signal transduction mechanism resulting in delayed cell damage, whereas decreased PLC levels later after ischemia may reflect ongoing neurodegeneration.",
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author = "Frederick Sieber and Traystman, {Richard J.} and Martin, {Lee J}",
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TY - JOUR

T1 - Delayed neuronal death after global incomplete ischemia in dogs is accompanied by changes in phospholipase C protein expression

AU - Sieber, Frederick

AU - Traystman, Richard J.

AU - Martin, Lee J

PY - 1997/5

Y1 - 1997/5

N2 - Activation of phospholipase C (PLC) increases intracellular Ca++ and may play a role in delayed neuronal death after ischemia. Because changes in intracellular Ca++ are believed to participate in ischemic neuronal injury, we tested the hypothesis that PLCβ protein levels are temporally altered in brain regions that undergo neurodegeneration after global in complete ischemia. Dogs (n = 12) were subjected to 20 minutes of global incomplete ischemia followed by recovery of either 1 (n = 5) or 7 days (n = 7). Six sham-operated animals were used as nonischemic controls. In hematoxylin and eosinstained brian sections, neuronal density at 1 day after ischemia was unchanged relative to nonischemic controls in hippocampus CA1, caudate and cerebellar cortex (anterior lobule). How ever, at 7 days after ischemia, neuronal densities were decreased to 56 ± 15% (mean ± SD) and 75 ± 17% of control in CA1 and caudate, respectively. At 1 and 7 days after ischemia the percentage of neurons showing ischemic injury increased from 13 ± 10 to 40 ± 35% in CA1, 24 ± 25 to 59 ± 16% in cerebellum and 4 ± 2 to 18 ± 12% in caudate. Densitometric analysis of immunocytochemically stained brain sections from controls (n = 3). 1 day after ischemia (n = 3) and 7 days after ischemia (n = 5) revealed that PLCβ immunoreactivity was increased in cerebellum at 1 day (0.274 ± 0.013 ν 0.295 ± 0.005 optical density units [OD] in control and 1 day, respectively) and 7 days (0.108 ± 0.009 ν 0.116 ± 0.005 OD in control and 7 days, respectively). PLCβ immunoreactivity was unchanged after ischemia in caudate and hippocampus. Western blot analysis of PLCβ immunoreactivity in the cerebellar cortex and hippocampus in the control (n = 3). 1 day (n = 2) and 7 days after ischemia (n = 2) groups showed that PLCβ levels were increased after ischemia in cerebellum 266% and 227% above control at 1 and 7 days, respectively. However in hippocampus. PLC expression after ischemia was unchanged at 97% and 84% of control at 1 and days, respectively. These results show that delayed neuronal degeneration after global incomplete ischemia is accompanied by regional abnormalities in PLC levels. Elevated PLC levels early may represent an aberrant signal transduction mechanism resulting in delayed cell damage, whereas decreased PLC levels later after ischemia may reflect ongoing neurodegeneration.

AB - Activation of phospholipase C (PLC) increases intracellular Ca++ and may play a role in delayed neuronal death after ischemia. Because changes in intracellular Ca++ are believed to participate in ischemic neuronal injury, we tested the hypothesis that PLCβ protein levels are temporally altered in brain regions that undergo neurodegeneration after global in complete ischemia. Dogs (n = 12) were subjected to 20 minutes of global incomplete ischemia followed by recovery of either 1 (n = 5) or 7 days (n = 7). Six sham-operated animals were used as nonischemic controls. In hematoxylin and eosinstained brian sections, neuronal density at 1 day after ischemia was unchanged relative to nonischemic controls in hippocampus CA1, caudate and cerebellar cortex (anterior lobule). How ever, at 7 days after ischemia, neuronal densities were decreased to 56 ± 15% (mean ± SD) and 75 ± 17% of control in CA1 and caudate, respectively. At 1 and 7 days after ischemia the percentage of neurons showing ischemic injury increased from 13 ± 10 to 40 ± 35% in CA1, 24 ± 25 to 59 ± 16% in cerebellum and 4 ± 2 to 18 ± 12% in caudate. Densitometric analysis of immunocytochemically stained brain sections from controls (n = 3). 1 day after ischemia (n = 3) and 7 days after ischemia (n = 5) revealed that PLCβ immunoreactivity was increased in cerebellum at 1 day (0.274 ± 0.013 ν 0.295 ± 0.005 optical density units [OD] in control and 1 day, respectively) and 7 days (0.108 ± 0.009 ν 0.116 ± 0.005 OD in control and 7 days, respectively). PLCβ immunoreactivity was unchanged after ischemia in caudate and hippocampus. Western blot analysis of PLCβ immunoreactivity in the cerebellar cortex and hippocampus in the control (n = 3). 1 day (n = 2) and 7 days after ischemia (n = 2) groups showed that PLCβ levels were increased after ischemia in cerebellum 266% and 227% above control at 1 and 7 days, respectively. However in hippocampus. PLC expression after ischemia was unchanged at 97% and 84% of control at 1 and days, respectively. These results show that delayed neuronal degeneration after global incomplete ischemia is accompanied by regional abnormalities in PLC levels. Elevated PLC levels early may represent an aberrant signal transduction mechanism resulting in delayed cell damage, whereas decreased PLC levels later after ischemia may reflect ongoing neurodegeneration.

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