Blockade of N-Methyl-D-Aspartate Receptor Prevents Hypoxic Neuronal Death and Cytokine Release

• Published in: Neuroimmunomodulation 1997-07, Vol.4 (4), p.195-199
• Main Authors: Di Loreto, Silvia, Balestrino, Maurizio, Pellegrini, Patrizia, Berghella, Anna Maria, Del Beato, Tiziana, Di Marco, Franca, Adorno, Domenico
• Format: Article
• Language: English
• Subjects: 2-Amino-5-phosphonovalerate - pharmacology; Animals; Cell Death - drug effects; Cells, Cultured; Cytokines - metabolism; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - pathology; Hypoxia, Brain - metabolism; Hypoxia, Brain - prevention & control; Linear Models; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Original Paper; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors
• ISSN: 1021-7401; 1423-0216
• DOI: 10.1159/000097338

Neuronal mortality, interleukin-1Β (IL-1Β) and tumor necrosis factor-Α (TNFΑ) release were measured in hypoxic hippocampal neuronal cultures. Release of IL1Β and TNFΑ was already observed in normoxic cultures, but after hypoxia it was increased approximately 2-fold. Pretreatment with 2-amino-5-phosphonovaleric acid (APV), the N-methyl-D-aspartate (NMDA) receptor antagonist, not only decreased neuronal mortality as expected, but also dramatically lowered cytokine release. However, there was no relationship between the neuronal mortality and the release of each cytokine both in untreated hypoxic cultures and in APV-pretreated ones. We conclude that IL1Β and TNFΑ release in hypoxia are dependent on the activation of the NMDA receptor, but that this is not the main mechanism of hypoxia damage in in vitro neuronal cultures.