In vivo cellular uptake of glutamate is impaired in the rat hippocampus during and after transient cerebral ischemia: a microdialysis extraction study.

Abstract

Using microdialysis in CA1 of the rat hippocampus, we studied the effect of transient cerebral ischemia on in vivo uptake and on extracellular levels of glutamate during, and at different time points after ischemia. (3)H-D-aspartate (test substance), and (14)C-mannitol (reference substance), were added to the dialysis perfusate, and the cellular extraction of (3)H-D-aspartate was calculated from scintillation analysis of fractionated dialysate samples. The extraction of (3)H-D-aspartate was studied both in a tracer like condition with a perfusate concentration of 0.2 microM, and in a condition of high saturation level, with 1.0 mM D-aspartate added to the perfusate. In between radioisotope perfusions, dialysate was sampled for analysis of amino acid content by HPLC. During ischemia, extraction of (3)H-D-aspartate (0.2 microM) declined to a maximum reduction of 68%. In the hours after ischemia, extraction of (3)H-D-aspartate (0.2 microM) was decreased by 32%. In the days after ischemia, there was a progressive decline in extraction of (3)H-D-aspartate (1.0 mM), reaching a reduction of 89% on Day 4 after ischemia. Extracellular glutamate remained at control levels at all time points after ischemia. The present study is the first to investigate uptake of glutamate in the intact rat brain in relation to cerebral ischemia. Evidence is provided that uptake of Glu is restrained during ischemia, and that in the hours after ischemia, the extracellular turnover of glutamate is decreased. In the course of the days after ischemia, degeneration of CA1 pyramidal cells occurs concomitantly with a progressive decline in glutamate transport ability, possibly of pathogenetic importance to CA1 pyramidal cell loss.

• Authors: T Bruhn, T Christensen, N H Diemer
• Journal: Journal of neuroscience research (J Neurosci Res) Vol. 66 Issue 6 Pg. 1118-26 (Dec 15 2001) ISSN: 0360-4012 [Print] United States
• PMID: 11746444 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2001 Wiley-Liss, Inc.

Chemical References

• Carrier Proteins
• Enzyme Inhibitors
• Tritium
• Aspartic Acid
• Glutamic Acid

Topics

• Animals
• Aspartic Acid (pharmacokinetics)
• Brain Ischemia (metabolism, physiopathology)
• Carrier Proteins (antagonists & inhibitors, metabolism)
• Enzyme Inhibitors (pharmacology)
• Extracellular Space (drug effects, metabolism)
• Glutamic Acid (metabolism)
• Hippocampus (drug effects, metabolism, physiopathology)
• Male
• Microdialysis
• Nerve Degeneration (metabolism, physiopathology)
• Presynaptic Terminals (drug effects, metabolism)
• Rats
• Rats, Wistar
• Synaptic Transmission (drug effects, physiology)
• Tritium (pharmacokinetics)