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

Am J Physiol Heart Circ Physiol. 2000 Sep;279(3):H1346-54. doi: 10.1152/ajpheart.2000.279.3.H1346.

Abstract

Brain extraction of (18)F-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 [(14)C]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 micromol. min(-1). g(-1)) than in control animals (1.74 +/- 0.26 micromol. 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 micromol. min(-1). g(-1)) than control subcortex (1.80 +/- 0.25 micromol. 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%.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-Butanol / administration & dosage
  • Acute Disease
  • Animals
  • Blood-Brain Barrier* / physiology*
  • Brain / metabolism*
  • Brain Chemistry
  • Carbon Radioisotopes
  • Carotid Arteries
  • Catheterization
  • Diazepam / administration & dosage
  • Electroencephalography
  • Fluorine Radioisotopes
  • Fluorodeoxyglucose F18 / administration & dosage
  • Fluorodeoxyglucose F18 / pharmacokinetics
  • Injections, Intra-Arterial
  • Injections, Intravenous
  • Jugular Veins
  • Male
  • Monosaccharide Transport Proteins / metabolism*
  • Pentylenetetrazole
  • Rats
  • Rats, Sprague-Dawley
  • Seizures / chemically induced
  • Seizures / metabolism*
  • Tritium
  • Up-Regulation*

Substances

  • Carbon Radioisotopes
  • Fluorine Radioisotopes
  • Monosaccharide Transport Proteins
  • Fluorodeoxyglucose F18
  • Tritium
  • 1-Butanol
  • Diazepam
  • Pentylenetetrazole