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• W1996581137 endingPage "e75739" @default.
• W1996581137 startingPage "e75739" @default.
• W1996581137 abstract "Spreading depolarizations (SDs) are coordinated depolarizations of brain tissue that have been well-characterized in animal models and more recently implicated in the progression of stroke injury. We previously showed that extracellular Zn2+ accumulation can inhibit the propagation of SD events. In that prior work, Zn2+ was tested in normoxic conditions, where SD was generated by localized KCl pulses in oxygenated tissue. The current study examined the extent to which Zn2+ effects are modified by hypoxia, to assess potential implications for stroke studies. The present studies examined SD generated in brain slices acutely prepared from mice, and recordings were made from the hippocampal CA1 region. SDs were generated by either local potassium injection (K-SD), exposure to the Na+/K+-ATPase inhibitor ouabain (ouabain-SD) or superfusion with modified ACSF with reduced oxygen and glucose concentrations (oxygen glucose deprivation: OGD-SD). Extracellular Zn2+ exposures (100 µM ZnCl2) effectively decreased SD propagation rates and significantly increased the initiation threshold for K-SD generated in oxygenated ACSF (95% O2). In contrast, ZnCl2 did not inhibit propagation of OGD-SD or ouabain-SD generated in hypoxic conditions. Zn2+ sensitivity in 0% O2 was restored by exposure to the protein oxidizer DTNB, suggesting that redox modulation may contribute to resistance to Zn2+ in hypoxic conditions. DTNB pretreatment also significantly potentiated the inhibitory effects of competitive (D-AP5) or allosteric (Ro25-6981) NMDA receptor antagonists on OGD-SD. Finally, Zn2+ inhibition of isolated NMDAR currents was potentiated by DTNB. Together, these results suggest that hypoxia-induced redox modulation can influence the sensitivity of SD to Zn2+ as well as to other NMDAR antagonists. Such a mechanism may limit inhibitory effects of endogenous Zn2+ accumulation in hypoxic regions close to ischemic infarcts." @default.
• W1996581137 created "2016-06-24" @default.
• W1996581137 creator A5061055260 @default.
• W1996581137 creator A5080852193 @default.
• W1996581137 date "2013-11-22" @default.
• W1996581137 modified "2023-10-15" @default.
• W1996581137 title "Hypoxia Limits Inhibitory Effects of Zn2+ on Spreading Depolarizations" @default.
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• W1996581137 doi "https://doi.org/10.1371/journal.pone.0075739" @default.
• W1996581137 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3838375" @default.
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• W1996581137 hasPublicationYear "2013" @default.
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