Flow threshold for enhanced phorbol ester binding in the ischemic gerbil brain |
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Authors: | Kortaro Tanaka MD Yasuo Fukuuchi Shintaro Gomi Shutaro Takashima Ban Mihara Toshitaka Shirai Shigeru Nogawa Hiroyuki Nozaki Eiichiro Nagata Taro Kondo |
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Institution: | (1) Department of Neurology, School of Medicine, Keio University, 35 Shinanomachi, 160 Shinjuku-ku, Tokyo, Japan |
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Abstract: | The correlation between regional phorbol ester binding and cerebral blood flow (CBF) was evaluated in the gerbil brain after 2-hour unilateral common carotid artery occlusion 3H]phorbol 12, 13-dibutyrate (PDBu) was used as a specific ligand for estimating the translocation of protein kinase C (PKC), and CBF was determined by the 14C]iodoantipyrine method. A quantitative autoradiographic method permitted concurrent measurement of these two parameters in the same brain. In the ischemia group of the animals, statistically significant, inverse correlations were noted between the CBF and PDBu binding in the hippocampus (CA1 and CA3 regions and dentate gyrus), the caudate-putamen and lateral nuclei of the thalamus. In these regions, the PDBu binding increased progressively as CBF fell below 35–40 ml/100 g/min. On the other hand, the PDBu binding in the cerebral cortices did not show any significant changes even when CBF was decreased to below 35 ml/100 g/min. The above data suggest that (1) the translocation of PKC to the cell membrane may be regionally specific in response to ischmia and may remain in the regions particularly vulnerable to ischemia such as the hippocampus, caudate-putamen and lateral nuclei of the thalamus in the early ischemic phase; (2) the threshold of CBF below which PKC begins to translocate to the cell membrane in the above regions, may be 35–40 ml/100 g/min in 2-hour ischemia. |
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Keywords: | Cerebral ischemia second messenger phorbol ester protein kinase C autoradiography cerebral blood flow |
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