Oral administration of glutathione improves memory deficits following transient brain ischemia by reducing brain oxidative stress

Y. Yabuki, K. Fukunaga

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

Abstract

Oxidative stress aggravates brain injury following ischemia. The glutathione (GSH) system plays a pivotal role in combating oxidative stress in various cell types. To determine whether oral GSH administration elicits anti-oxidative effects, we assessed its potential neuroprotective effects in transient bilateral common carotid artery occlusion (BCCAO) mice. In naïve mice, acute oral administration of GSH significantly increased GSH levels by 1. h in the cortex and hippocampus. Eleven days after BCCAO, untreated mice showed significantly decreased GSH levels and an inverse elevation of glutathione-disulfide (GSSG) levels in both the cortex and hippocampus. Oral administration of GSH (100 and 500. mg/kg p.o.) for 10 consecutive days after ischemia restored reduced GSH levels and inhibited GSSG elevation. Notably, post-administration of GSH (100 and 500. mg/kg p.o.) significantly prevented neuronal cell death in the hippocampal CA1 region in BCCAO mice, an effect closely correlated with decreased levels of oxidative markers such as 4-hydroxy-2-nonenal (4-HNE), 8-hydroxy-2-deoxyguanosine (8-OHdG) and nitrotyrosine in that region. Finally, GSH administration for 10. days improved memory deficits observed in BCCAO mice. Taken together, our findings indicate that the anti-oxidative effect of oral GSH administration ameliorates post-ischemia neuronal cell death and, in turn, may improve memory.

Original languageEnglish
Pages (from-to)394-407
Number of pages14
JournalNeuroscience
Volume250
DOIs
Publication statusPublished - 2013 Oct

Keywords

  • Bilateral common carotid arteries occlusion
  • Ca/calmodulin-dependent protein kinase II
  • Glutathione
  • Neuroprotection
  • Oxidative stress

ASJC Scopus subject areas

  • Neuroscience(all)

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