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

Abstract

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 ( K m) was unchanged by PTZ, we derived estimates of 1) treated and 2) control maximal transporter velocities ( V max) and 3) a single K m. In cortex, the glucose transporter V max 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 K m = 9.5 ± 1.6 mM. Blood-brain barrier (BBB) V max 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 V max and BBB glucose permeability increase by 30–40%.