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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-2-28
pubmed:abstractText
PK11195, a selective PBR ligand, has been reported to exert a protective effect against the neuronal damage induced by the intrastriatal infusion of quinolinic acid, an excitatory amino acid. The neuroprotective effect of PK11195 observed at 48 h after the infusion was mediated by the inhibition of microglial activation. The aim of this study is to search the mechanism for the effect of PK11195 other than the inhibition of activation of microglia. In this study, the effect of PK11195 on glucose metabolism as well as neuroprotection in the early phase (2 h) after the injection of quinolinic acid was examined. Intrastriatal injection of quinolinic acid (60 nmol/microL) alone caused a significant enhancement of [(14)C]DG utilization in the infused striatum (about 160% vs. the contralateral side). This enhancement of glucose utilization might be due to an increase in phosphorylation rate of [(14)C]DG rather than delivery process from the plasma into the brain, since the initial uptake of [(14)C]DG (1 min) was not changed by quinolinic acid. Coinjection of PK11195 (10 nmol/microL) completely blocked the enhancement of [(14)C]DG uptake induced by quinolinic acid. The attenuating effect of PK11195 on glucose metabolic disturbance induced by quinolinic acid seemed to be related to voltage-dependent anion channels (VDAC), which are component of the PBR complex and associated with the regulation of hexokinase activity. PK11195 also showed neuroprotective effect at 2 h after the infusion of quinolinic acid, despite no significant activation of microglia was observed at this time-point. Thus, the neuroprotection of PK11195 might be related to normalization of the metabolic disturbance by the excitatory amino acid.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0887-4476
pubmed:author
pubmed:issnType
Print
pubmed:volume
62
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
253-8
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Effect of PK11195 on attenuating the enhancement of glucose utilization induced by quinolinic acid infusion in the rat brain.
pubmed:affiliation
Graduate School of Medicine, Osaka University, 1-7 Yamadaoka, Suita, Osaka, Japan. amitani@sahs.med.osaka-u.ac.jp
pubmed:publicationType
Journal Article