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 language | English (US) |
|---|---|
| Pages (from-to) | 527-533 |
| Number of pages | 7 |
| Journal | Journal of Cerebral Blood Flow and Metabolism |
| Volume | 17 |
| Issue number | 5 |
| State | Published - May 1997 |
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Keywords
- CA1
- intracellular Ca homeostasis
- ischemic neurodegeneration
- signal transdiction
ASJC Scopus subject areas
- Endocrinology
- Neuroscience(all)
- Endocrinology, Diabetes and Metabolism
Cite this
Delayed neuronal death after global incomplete ischemia in dogs is accompanied by changes in phospholipase C protein expression. / Sieber, Frederick; Traystman, Richard J.; Martin, Lee J.
In: Journal of Cerebral Blood Flow and Metabolism, Vol. 17, No. 5, 05.1997, p. 527-533.Research output: Contribution to journal › Article
}
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.
KW - CA1
KW - intracellular Ca homeostasis
KW - ischemic neurodegeneration
KW - signal transdiction
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M3 - Article
C2 - 9183290
AN - SCOPUS:0030991526
VL - 17
SP - 527
EP - 533
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
SN - 0271-678X
IS - 5
ER -