Hypoxia/reoxygenation induces nitric oxide and TNF-α release from cultured microglia but not astrocytes of the rat

Ju Yu Wang, Jia Yi Wang

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


Hypoxia/reoxygenation (H/R) elicits neuronal cell injury and glial cell activation within the central nervous system (CNS). Neuroinflammation is a process that primarily results from the acute or chronic activation of glial cells. This overactive state of glial cells results in the increased release of nitric oxide (NO) and/or tumor necrosis factor alpha (TNF-α), a process which can lead to neuronal damage or death. In this study, we found that hypoxia for eight or twelve hours (h) followed by 24 h reoxygenation (H8/R24 or H12/R24) induced NO production and TNF-α release from cultures of enriched microglial or mixed glial cells. However, microglial cells could not survive longer periods of hypoxia (≥ 12 h) in microglia-enriched culture. While astrocytes retained a 95 % viability following longer periods of H/R in astrocyte-enriched cultures, they did not produce any significant quantities of NO and TNF-α. Reoxygenation for prolonged periods (three and five days) following H24 resulted in progressively greater increases in NO production (about two-fold greater level in hypoxia as compared to normoxic conditions) accompanied by relatively less increases in TNF-α release in mixed glial cell cultures. Our data indicate that inflammatory mediators such as NO and TNF-α are released from glia-enriched mix culture in response to H/R. While microglial cells are more vulnerable than astrocytes during H/R, they survive longer in the presence of astrocyte and are the major cell type producing NO and TNF-α. Furthermore, the TNF-α release precedes NO production in response to a prolonged duration of reoxygenation following hypoxia for 24 h.

Original languageEnglish
Pages (from-to)127-134
Number of pages8
JournalChinese Journal of Physiology
Issue number3
Publication statusPublished - 2007
Externally publishedYes


  • Astrocyte
  • Hypoxia-reoxygenation
  • Microglial cell
  • NO
  • TNF-α

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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