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Original Article

Exp Neurobiol 2020; 29(1): 70-79

Published online February 29, 2020

https://doi.org/10.5607/en.2020.29.1.70

© The Korean Society for Brain and Neural Sciences

Expression of Cellular Receptors in the Ischemic Hemisphere of Mice with Increased Glucose Uptake

Jin Soo Lee1,2,*, Ji Man Hong1,2, Bok Seon Yoon1,2, Keoung Sun Son1,2, Kyung Eon Lee3, Doo Soon Im4, Bok-Nam Park5, Young-Sil An5, Dong Hoon Hwang6, Chan Bae Park7, Byung Gon Kim2,6 and Eun-hye Joe2,6,8

1Department of Neurology, Ajou University School of Medicine, 2Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 16499, 3School of Pharmacy, Kyung Hee University, Seoul 02447, Korea, 4Department of Cellular & Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada, 5Department of Nuclear Medicine and Molecular Imaging, Ajou University School of Medicine, 6Department of Brain Science, Ajou University School of Medicine, 7Department of Biology, Ajou University School of Medicine, 8Department of Pharmacology, Ajou University School of Medicine, Suwon 16499, Korea

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-31-219-5175, FAX: 82-31-219-5178
e-mail: jinsoo22@gmail.com

Received: September 30, 2019; Revised: January 16, 2020; Accepted: February 6, 2020

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License
(http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and
reproduction in any medium, provided the original work is properly cited.

Many previous studies have shown reduced glucose uptake in the ischemic brain. In contrast, in a permanent unilateral common carotid artery occlusion (UCCAO) mouse model, our pilot experiments using 18F-fluorodeoxyglucose positron emission tomography (FDG PET) revealed that a subset of mice exhibited conspicuously high uptake of glucose in the ipsilateral hemisphere at 1 week post-occlusion (asymmetric group), whereas other mice showed symmetric uptake in both hemispheres (symmetric group). Thus, we aimed to understand the discrepancy between the two groups. Cerebral blood flow and histological/metabolic changes were analyzed using laser Doppler flowmetry and immunohistochemistry/Western blotting, respectively. Contrary to the increased glucose uptake observed in the ischemic cerebral hemisphere on FDG PET (p<0.001), cerebral blood flow tended to be lower in the asymmetric group than in the symmetric group (right to left ratio [%], 36.4±21.8 vs. 58.0±24.8, p=0.059). Neuronal death was observed only in the ischemic hemisphere of the asymmetric group. In contrast, astrocytes were more activated in the asymmetric group than in the symmetric group (p<0.05). Glucose transporter-1, and monocarboxylate transporter-1 were also upregulated in the asymmetric group, compared with the symmetric group (p<0.05, respectively). These results suggest that the increased FDG uptake was associated with relatively severe ischemia, and glucose transporter-1 upregulation and astrocyte activation. Glucose metabolism may thus be a compensatory mechanism in the moderately severe ischemic brain.

Graphical Abstract


Keywords: Brain ischemia, 4-fluoro-4-deoxyglucose, Positron-emission tomography, Glucose transporter type 1, Astrocytes