Interleukin-1β but not tumor necrosis factor-α potentiates neuronal damage by quinolinic acid: Protection by an adenosine A2A receptor antagonist
| Autor: | Trevor W. Stone, Wilhelmina M.H. Behan |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Agonist Receptor Adenosine A2A medicine.drug_class Interleukin-1beta Neurotoxins Excitotoxicity Adenosine A2A receptor Pharmacology Biology medicine.disease_cause Hippocampus Brain Ischemia Cellular and Molecular Neuroscience chemistry.chemical_compound Kynurenic acid medicine Animals Rats Wistar Triazines Tumor Necrosis Factor-alpha Pyramidal Cells Glutamate receptor Drug Synergism Quinolinic Acid Triazoles Receptor antagonist Adenosine A2 Receptor Antagonists Rats Neuroprotective Agents nervous system Biochemistry chemistry Cytoprotection Brain Injuries Nerve Degeneration NMDA receptor Quinolinic acid |
| Zdroj: | Journal of Neuroscience Research. 85:1077-1085 |
| ISSN: | 1097-4547 0360-4012 |
| DOI: | 10.1002/jnr.21212 |
| Popis: | Quinolinic acid is an agonist at glutamate receptors sensitive to N-methyl-D-aspartate (NMDA). It has been implicated in neural dysfunction associated with infections, trauma, and ischemia, although its neurotoxic potency is relatively low. This study was designed to examine the effects of a combination of quinolinic acid and the proinflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). Compounds were administered to the hippocampus of anesthetized male rats, animals being allowed to recover for 7 days before histological analysis of the hippocampus for neuronal damage estimated by counting of intact, healthy neurons. A low dose of quinolinic acid or IL-1beta produced no damage by itself, but the two together induced a significant loss of pyramidal neurons in the hippocampus. Higher doses produced almost total loss of pyramidal cells. Intrahippocampal TNF-alpha produced no effect alone but significantly reduced the neuronal loss produced by quinolinic acid. The adenosine A(2A) receptor antagonist ZM241385 reduced neuronal loss produced by the combinations of quinolinic acid and IL-1beta. The results suggest that simultaneous quinolinic acid and IL-1beta, both being induced by cerebral infection or injury, are synergistic in the production of neuronal damage and could together contribute substantially to traumatic, infective, or ischemic cerebral damage. Antagonism of adenosine A(2A) receptors protects neurons against the combination of quinolinic acid and IL-1beta. |
| Databáze: | OpenAIRE |
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