Acute upregulation of blood-brain barrier glucose transporter activity in seizures.
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%.
Cornford
E M
EM
Department of Neurology, University of California, Los Angeles School of Medicine, Los Angeles, 90095, USA. cornford@ucla.edu
Nguyen
E V
EV
Landaw
E M
EM
D020001:1-Butanol / Q000008:administration & dosage; D000208:Acute Disease; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D002250:Carbon Radioisotopes; D002339:Carotid Arteries; D002404:Catheterization; D003975:Diazepam / Q000008:administration & dosage; D004569:Electroencephalography; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18 / Q000008:administration & dosage / Q000493:pharmacokinetics; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D007601:Jugular Veins; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D010433:Pentylenetetrazole; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D014316:Tritium; D015854:Up-Regulation
D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D009004:Monosaccharide Transport Proteins; D019788:Fluorodeoxyglucose F18; D014316:Tritium; D020001:1-Butanol; D003975:Diazepam; D010433:Pentylenetetrazole