Therapeutic window for YC-1 following glutamate-induced neuronal damage and transient focal cerebral ischemia

Shih Huang Tai, Wei Ting Lee, Ai Chiang Lee, Yu Wen Lin, Hsin Yi Hung, Sheng Yang Huang, Tian Shung Wu, E. Jian Lee

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

3-(5'-Hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1), has been demonstrated to inhibit platelet aggregation, vascular contraction and hypoxia-inducible factor 1 activity in vitro and in vivo. The present study investigated the neuroprotective efficacy of YC-1 in cultured neurons exposed to glutamate-induced excitotoxicity and in an animal model of stroke. In a cortical neuronal culture model, YC-1 demonstrated neurotoxicity at a concentration >100 μM, and YC-1 (10-30 μM) achieved potent cytoprotection against glutamate-induced neuronal damage. Additionally, YC-1 (30 μM) effectively attenuated the increase in intracellular Ca2+ levels. Delayed treatment of YC-1 (30 μM) also protected against glutamate-induced neuronal damage and cell swelling in cultured neurons, though only at 4 h post-treatment. In addition, immediate treatment of YC-1 (30 μM) following the exposure of cortical neurons to glutamate (300 μM) produced a marked reduction in intracellular pH. Delayed treatment of YC-1 (25 mg/kg) protected against ischemic brain damage in vivo, though only when administered at 3 h post-insult. Thus, YC-1 exhibited neuroprotection against glutamate-induced neuronal damage and in mice subjected to transient focal cerebral ischemia. This neuroprotection may be mediated via its ability to limit the glutamate-induced excitotoxicity. However, the neuroprotective therapeutic window of YC-1 is only at 3 h in vivo and 4 h in vitro, which may, at least in part, be attributed to its ability to reduce the intracellular pH in the early phase of ischemic stroke. Although YC-1 provided the potential for clinical therapy, the treatment time point must be carefully evaluated following ischemia.

Original languageEnglish
Pages (from-to)6490-6496
Number of pages7
JournalMolecular Medicine Reports
Volume17
Issue number5
DOIs
Publication statusPublished - 2018 May

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Therapeutic window for YC-1 following glutamate-induced neuronal damage and transient focal cerebral ischemia'. Together they form a unique fingerprint.

Cite this