De-coupling of blood flow and metabolism in the rat brain induced by glutamate.
OBJECTIVE
Glutamate plays an essential role in neuronal cell death in many neurological disorders. In this study, we examined both glucose metabolism and cerebral blood flow in the same rat following infusion of glutamate or ibotenic acid using the dual-tracer technique. The effects of MK-801, an NMDA receptor antagonist, and NBQX, an AMPA-kainate receptor antagonist, on the changes in the glucose metabolism and cerebral blood flow induced by glutamate were also examined.


METHODS
The rats were microinjected with glutamate (1 micromol/microl, 2 microl) or ibotenic acid (10 microg/microl, 1 microl) into the right striatum, and dual-tracer autoradiograms of [(18)F]FDG and [(14)C]IMP were obtained. MK-801 and NBQX were injected intravenously about 45 and 30 min, respectively, after the infusion of glutamate.


RESULTS
De-coupling of blood flow and metabolism was noted in the glutamate-infused hemisphere (as assessed by no alteration of [(18)F]FDG uptake and significant decrease of [(14)C]IMP uptake). Pretreatments with MK-801, NBQX, or combined use of MK-801 and NBQX did not affect the de-coupling of the blood flow and metabolism induced by glutamate. A histochemical study revealed that about 20% neuronal cell death had occurred in the striatum at 105 min after the infusion of glutamate. In addition, a significant increase of the [(18)F]FDG uptake and decrease of [(14)C]IMP uptake were also seen in the rat brain infused with ibotenic acid.


CONCLUSIONS
These results indicate that glutamate and ibotenic acid caused a significant de-coupling of blood flow and glucose metabolism in the intact rat brain during the early phase of neurodegeneration. It is necessary to evaluate the relation between metabotropic glutamate receptors and de-coupling of blood flow and metabolism.
Hirose
Shinichiro
S
Division of Health Sciences, Graduate School of Medicine, Osaka University, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan. hirose@sahs.med.osaka-u.ac.jp
Momosaki
Sotaro
S
Sasaki
Kazunari
K
Hosoi
Rie
R
Abe
Kohji
K
Gee
Antony
A
Inoue
Osamu
O
D000662:Amphetamines / Q000737:chemistry; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000098:blood supply / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000737:chemistry; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D011810:Quinoxalines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D000662:Amphetamines; D002250:Carbon Radioisotopes; D016291:Dizocilpine Maleate; D019788:Fluorodeoxyglucose F18; D005947:Glucose; D018698:Glutamic Acid; D011810:Quinoxalines; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C041336:4-iodoamphetamine