Exp Neurobiol.  2020 Feb;29(1):70-79. 10.5607/en.2020.29.1.70.

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

Affiliations
  • 1Department of Neurology, Ajou University School of Medicine, Korea
  • 2Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 16499, Korea
  • 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, Korea
  • 6Department of Brain Science, Ajou University School of Medicine, Korea
  • 7Department of Biology, Ajou University School of Medicine, Korea
  • 8Department of Pharmacology, Ajou University School of Medicine, Suwon 16499, Korea

Abstract

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.

Keyword

Brain ischemia; 4-fluoro-4-deoxyglucose; Positron-emission tomography; Glucose transporter type 1; Astrocytes
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