Abstract
The neuroprotective effects of two kynurenine hydroxylase inhibitors, (m-nitrobenzoyl)-alanine (mNBA) and 3,4-dimethoxy-[-N-4-(nitrophenyl)thiazol-2yl]-benzenesulfonamide (Ro 61-8048), were studied in vitro and in vivo. In organotypic hippocampal slice cultures deprived of oxygen and glucose, these inhibitors significantly reduced neuronal damage. In gerbils subjected to bilateral carotid occlusion for 5 min, the administration of mNBA (400mg/kg i.p., 3 times) or Ro 61-8048 (40mg/kg i.p., 3 times) dramatically decreased the percentage of damaged pyramidal neurones in the hippocampal CA1 region. Finally, in rats with permanent occlusion of the middle cerebral artery, mNBA (200-400mg/kg i.p.) and Ro 61-8048 (40mg/kg i.p.) administration reduced the infarct volume. Our results demonstrate that ischemic neuronal damage may be significantly decreased by inhibiting kynurenine hydroxylase.
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Moroni, F., Cozzi, A., Peruginelli, F. (1999). Neuroprotective Effects of Kynurenine-3-Hydroxylase Inhibitors in Models of Brain Ischemia. In: Huether, G., Kochen, W., Simat, T.J., Steinhart, H. (eds) Tryptophan, Serotonin, and Melatonin. Advances in Experimental Medicine and Biology, vol 467. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4709-9_26
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DOI: https://doi.org/10.1007/978-1-4615-4709-9_26
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