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Am J Physiol Heart Circ Physiol 279: H1346-H1354, 2000;
0363-6135/00 $5.00
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Vol. 279, Issue 3, H1346-H1354, September 2000

Acute upregulation of blood-brain barrier glucose transporter activity in seizures

Eain M. Cornford1,2,3, Eddy V. Nguyen1,3, and Elliot M. Landaw4

Departments of 1 Neurology, 4 Biomathematics, and the 2 Brain Research Institute, University of California, Los Angeles School of Medicine, Los Angeles 90095, and 3 Southwest Regional Veterans Administration Epilepsy Center, Neurology Service, Veterans Administration West Los Angeles Medical Center, Los Angeles, California 90073

Brain extraction of 18F-labeled 2-fluoro-2-deoxy-D-glucose (FDG) was significantly higher in pentylene tetrazole (PTZ)-treated rats (32 ± 4%) than controls (25 ± 4%). The FDG permeability-surface area product (PS) was also significantly higher with PTZ treatment (0.36 ± 0.05 ml · min-1 · g-1) than in controls (0.20 ± 0.06 ml · min-1 · g-1). Cerebral blood flow rates were also elevated by 50% in seizures. The internal carotid artery perfusion technique indicated mean [14C]glucose clearance (and extraction) was increased with PTZ treatment, and seizures increased the PS by 37 ± 16% (P < 0.05) in cortical regions. Because kinetic analyses suggested the glucose transporter half-saturation constant (Km) was unchanged by PTZ, we derived estimates of 1) treated and 2) control maximal transporter velocities (Vmax) and 3) a single Km. In cortex, the glucose transporter Vmax was 42 ± 11% higher (P < 0.05) in PTZ-treated animals (2.46 ± 0.34 µmol · min-1 · g-1) than in control animals (1.74 ± 0.26 µmol · min-1 · g-1), and the Km = 9.5 ± 1.6 mM. Blood-brain barrier (BBB) Vmax was 31 ± 10% greater (P < 0.05) in PTZ-treated (2.36 ± 0.30 µmol · min-1 · g-1) than control subcortex (1.80 ± 0.25 µmol · min-1 · g-1). We conclude acute upregulation of BBB glucose transport occurs within 3 min of an initial seizure. Transporter Vmax and BBB glucose permeability increase by 30-40%.

blood-brain barrier glucose transporter; maximal velocity; half-saturation constant; pentylene tetrazole seizures; unsaturated permeability-surface area products; transporter recruitment; intrinsic activity


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