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11 Munn, D. H. et al. Prevention of allogeneic fetal rejection by tryptophan catabolism. Science 281, 1191–1193 (1998).One of the clearest links between activation of the kynurenine pathway and modulation of the physiological/immune axis, with devastating pathological consequences.

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34 Espey, M. G., Moffett, J. R. & Namboodiri, M. A. A. Temporal and spatial changes of quinolinic acid immunoreactivity in the immune system of lipopolysaccharide-stimulated mice. J. Leukocyte Biol. 57, 199–206 (1995).

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36 Heyes, M. P. et al. Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurologic disease. Brain 115, 1249–1273 (1992).An extensive study of the potential contribution of quinolinic acid to inflammatory brain disorders.

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44 Nicholls, T., Nitsos, I. & Walker, D. W. Tryptophan metabolism in pregnant sheep: increased fetal kynurenine production in response to maternal tryptophan loading. Am. J. Obst. Gyn. 181, 1452–1460 (1999).

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47 Scharfman, H. E., Hodgkin, P. S., Lee, S.-C. & Schwarcz, R. Quantitative differences in the effects of de novo produced and exogenous kynurenic acid in rat brain slices. Neurosci. Lett. 274, 111–114 (1999).A study that shows that the effects of endogenously generated kynurenines are far more effective than those added exogenously, which has implications for appreciating the potential functional disturbances that could follow alterations in their endogenous concentrations.

48 Schwarcz, R. et al. Modulation and function of kynurenic acid in the immature rat brain. Adv. Exp. Med. Biol. 467, 113–123 (1999).

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52 Hilmas, C. et al. The brain metabolite kynurenic acid inhibits α7-nicotinic receptor activity and increases non-α7-nicotinic receptor expression: pathophysiological implications. J. Neurosci. 21, 7463–7473 (2001).One of the recent papers to propose an important site of action of kynurenic acid other than its blockade of glutamate receptors.

53 Erhardt, S., Oberg, H. & Engberg, G. Pharmacologically elevated levels of endogenous kynurenic acid prevent nicotine-induced activation of nigral dopamine neurones. Arch. Pharmacol. 363, 21–27 (2001)

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56 Chiarugi, A., Meli, E. & Moroni, F. Similarities and differences in the neuronal death processes activated by 3-hydroxykynurenine and quinolinic acid. J. Neurochem. 77, 1310–1318 (2001).

57 Heyes, M. P. et al. Elevated CSF quinolinic acid levels are associated with region-specific cerebral volume loss in HIV infection. Brain Res. 124, 1033–1042 (2001).

58 Sardar, A. M. & Reynolds, G. P. Frontal cortex indoleamin-2,3-dioxygenase activity is increased in HIV-1-associated dementia. Neurosci. Lett. 187, 9–12 (1995).

59 Heyes, M. P. et al. Inter-relationships between neuroactive kynurenines, neopterin and 2-microglobulin in CSF and serum of HIV-1 infected patients. J. Neuroimmunol. 40, 71–80 (1992).

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61 Beal, M. F., Ferrante, R. J., Swartz, K. J. & Kowall, N. W. Chronic quinolinic acid lesions in rats closely resemble Huntington's Disease. J. Neurosci. 11, 1649–1659 (1991).A detailed analysis of the neurochemical changes after quinolinic acid administration compared with the changes in a major neurodegenerative disorder — Huntington's disease.

62 Nicholson, L. F. B., Faull, R. L. M., Waldvogel, H. J. & Dragunow, M. GABA and GABAA receptor changes in the substantia nigra of the rat following quinolinic acid lesions in the striatum closely resemble Huntington's disease. Neuroscience 66, 507–521 (1995).

63 Carlock, L., Walker, P. D., Shan, Y. & Gutridge, K. Transcription of the Huntington disease gene during the quinolinic acid excitotoxic cascade. Neuroreport 6, 1121–1124 (1995).

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78 Halperin, J. J. & Heyes, M. P. Neuroactive kynurenines in Lyme borreliosis. Neurology 42, 43–50 (1992).

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80 Heyes, M. P. & Nowak, T. S. Jr. Delayed increases in regional brain quinolinic acid follow transient ischemia in the gerbil. J. Cereb. Blood Flow Metab. 10, 660–667 (1990).A paper that highlights the fact that raised kynurenine-pathway activity can be part of a secondary, inflammatory response to tissue damage that could exacerbate or prolong that damage.

81 Baratte, S. et al. Temporal and spatial changes of quinolinic acid immunoreactivity in the gerbil hippocampus following transient cerebral ischemia. Mol. Brain Res. 59, 50–57 (1998).

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83 Sinz, E. H. et al. Quinolinic acid is increased in CSF and associated with mortality after traumatic brain injury in humans. J. Cereb. Blood Flow Metab. 18, 610–615 (1998).

84 Baran, H. et al. Increased kynurenic acid in the brain after neonatal asphyxia. Life Sci. 69, 1249–1256 (2001).

85 Ceresoli-Borroni, G. & Schwarcz, R. Neonatal asphyxia in rats: acute effects on cerebral kynurenine metabolism. Pediatr. Res. 50, 231–235 (2001).

86 Dang, Y., Dale, W. E & Brown, O. R. Comparative effects of oxygen on IDO and TDO of the kynurenine pathway. Free Radical Biol. Med. 28, 615–624 (2000).

87 Issa, F. et al. A multidimensional approach to analysis of CSF biogenic amines in schizophrenia. II. Correlations with psychopathology. Psychiatr. Res. 52, 251–258 (1994).

88 Erhardt, S. et al. Kynurenic acid levels are elevated in the cerebrospinal fluid of patients with schizophrenia. Neurosci. Lett. 313, 96–98 (2001).

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90 Maloney, A. M., St Claire Morgan, O., Widner, B., Werner, E. R. & Fuchs, D. CNS activation of the IDO pathway in human T cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis. J. Infect. Dis. 181, 2037–2040 (2000).

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104 Wu, H.-Q. et al. Kynurenergic manipulations influence excitatory synaptic function and excitotoxic vulnerability in the rat hippocampus in vivo. Neuroscience 97, 243–251 (2000).

105 Guidetti, F., Wu, H.-Q. & Schwarcz, R. In situ produced 7-chlorokynurenate provides protection against quinolinate and malonate-induced neurotoxicity in the rat striatum. Exp. Neurol. 163, 123–130 (2000).

106 Wu, H.-Q., Lee, S.-C. & Schwarcz, R. Systemic administration of 4-chlorokynurenine prevents quinolinic acid neurotoxicity in the rat hippocampus. Eur. J. Pharmacol. 390, 267–274 (2000).

107 Connick, J. H. et al. Nicotinylalanine increases cerebral kynurenic acid content and has anticonvulsant activity. Gen. Pharmacol. 23, 235–239 (1992).One of the first studies to show the principle that inhibition of the kynurenine pathway could increase kynurenic acid levels sufficiently to suppress neuronal overactivity and potential toxicity.

108 Russi, P. et al. Nicotinylalanine increases the formation of kynurenic acid in the brain and antagonizes convulsions. J. Neurochem. 59, 2076–2080 (1992).

109 Chiarugi, A., Carpenedo, R. & Moroni, F. Kynurenine disposition in blood and brain of mice: effects of selective inhibitors of kynurenine hydroxylase and kynurenase. J. Neurochem. 67, 692–698 (1996).

110 Cozzi, R., Carpenedo, R. & Moroni, F. Kynurenine hydroxylase inhibitors reduce ischaemic brain damage: studies with (m-nitrobenzoyl)alanine and 3,4-dimethoxy-[N-4-(nitrophenyl)thiazol-2-yl]-benzenesulfonamide (Ro 61-8048) in models of focal or global ischaemia. J. Cereb. Blood Flow Metab. 19, 771–777 (1999).An excellent example of the use of kynurenine-pathway inhibitors to prevent brain damage that is caused by ischaemia, implicating the pathway in the development of that damage.

111 Speciale, C. et al. (r,s)-3,4-dichlorobenzoylalanine (FCE 28833A) causes a large and persistent increase in brain kynurenic acid levels in rats. Eur. J. Pharmacol. 315, 263–267 (1996).

112 Rover, S., Cesura, A. M., Hugenin, P., Kettler, R. & Szente, A. Synthesis and biochemical evaluation of N-(4-phenylthiazol-2-yl)benzenesulfonamides as high-affinity inhibitors of kynurenine 3-hydroxylase. J. Med. Chem. 40, 4378–4385 (1997).

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