Effects of nitrobenzylthioinosine on adenosine levels and neuronal injury in rat forebrain ischemia

Yi Wei Zhang, P. Nicholas Shepel, James Peeling, Jonathan D. Geiger, Fiona E. Parkinson

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Nitrobenzylthioinosine (NBMPR) can potentiate the actions of adenosine through inhibition of adenosine influx mediated by the equilibrative nucleoside transporter subtype 1 (ENT1). As adenosine can decrease ischemic neuronal injury, we tested the hypothesis that peripheral administration of the pro-drug NBMPR-phosphate (NBMPR-P) can increase brain adenosine levels and reduce ischemia-induced loss of hippocampal CA1 neurons. Pre-ischemic, but not post-ischemic, peripheral administration of NBMPR-P significantly (P = 0.03) increased neuronal survival. Mechanistically, NBMPR-induced neuroprotection was associated with significant (P = 0.03) increases in adenosine levels relative to saline-treated controls. Hypothermia was tested for but did not account for the beneficial effects of NBMPR. Together, these data suggest that selective inhibition of ENT1 adenosine transporters can increase post-ischemic levels of adenosine and reduce ischemic neuronal death.

Original languageEnglish (US)
Pages (from-to)83-89
Number of pages7
JournalNeuroscience Research Communications
Volume30
Issue number2
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Adenosine
  • Cerebral ischemia
  • ENT1
  • Nucleoside transport

ASJC Scopus subject areas

  • Neuroscience(all)

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