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Expression of MCP-1 in the Hippocampus of SHRSP with Ischemia-Related Delayed Neuronal Death
Authors:Yasuko Sakurai-Yamashita  Kazuto Shigematsu  Kimihiro Yamashita  Masami Niwa
Affiliation:(1) Department of Pharmacology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan;(2) Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan;(3) Section of Pharmacology, Department of Environmental Conservation, Faculty of Environmental Studies, Nagasaki University, Nagasaki 852-8521, Japan;(4) Department of Pharmacology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan
Abstract:1. The expression of monocyte chemoattractant protein-1 (MCP-1) was examined in stroke-prone spontaneously hypertensive rats with transient global ischemia in order to study the involvement of the infiltration of blood monocytes in the mechanism of ischemia-related neuronal death.2. The brains of the animals with occlusion of the bilateral carotid arteries for 10 min were removed at 8 h, 1, 2, 4 and 7 days after reperfusion. Frozen sections were used for in situ hybridization and tissue specimens from the hippocampus and the cerebral cortex were used to measure the concentration of MCP-1 by ELISA.3. No MCP-1 mRNA was detected in the hippocampus of the sham group animals. One day after ischemia-reperfusion, MCP-1 mRNA was clearly expressed in the CA4 subfield and the molecular layer of the dentate gyrus, while it was slightly expressed in the lacnosum moleculare of the CA1 subfield. A dramatic expression was demonstrated in the entire CA1 subfield at 2 days after the operation. Most of the cells expressing MCP-1 were astrocytes. At 4 and 7 days after reperfusion, no MCP-1 mRNA was detected in the hippocampus. The concentration of MCP-1 protein dramatically increased in the hippocampus at 2 days after reperfusion.4. Taken together with the findings of our previous study showing an increased permeability of the blood-brain barrier in the hippocampus from 12 h after ischemia-reperfusion, the astrocytes expressing MCP-1 might therefore induce the migration of monocytes into the brain parenchyma. As a result, such astrocytes expressing MCP-1 may therefore be related to the pathological events of delayed neuronal death in the pyramidal neurons.
Keywords:stroke-prone spontaneously hypertensive rat  monocyte chemoattractant protein-1  astrocytes  ischemia  neuronal death  blood-brain barrier  brain
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