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Previous studies have shown that in rat cerebral cortical slices or a glia\u2010derived cell line, acute treatment with ammonia in vitro and in vivo inhibits the production of a broad\u2010spectrum antagonist of excitatory amino acid receptors, kynurenic acid (KYNA). The present study analyzed KYNA synthesis in cerebral cortical slices obtained from rats with progressing HE symptoms accompanying acute liver failure induced by one, two, or three intraperitoneal administrations of thioacetamide (TAA) at 24\u2010hr intervals. KYNA synthesis was found decreased to 83% of control 24 hr after one administration of TAA and unaffected after two TAA injections, when moderate hyperammonemia was associated by metabolic and bioelectric activation of the central nervous system, but was not accompanied by typical HE symptoms. KYNA synthesis was elevated to 155% of control after three TAA administrations, a period in which the rats showed advanced HE symptoms including stupor or coma. KYNA synthesis at the advanced HE stage was inhibited by glutamate in a degree comparable to that observed in control slices. The elevation of KYNA synthesis was associated with increased activity of a kynurenine aminotransferase (KAT) isomer, KAT\u2010II. KYNA synthesis did not differ from control 21 days after the third TAA administration when HE symptoms receded. The results suggest that alterations of KYNA synthesis may contribute to the imbalance between neural excitation and inhibition at different stages of HE. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.10862","type":"journal-article","created":{"date-parts":[[2004,1,21]],"date-time":"2004-01-21T10:00:45Z","timestamp":1074679245000},"page":"436-440","source":"Crossref","is-referenced-by-count":22,"title":["Kynurenic acid synthesis in cerebral cortical slices of rats with progressing symptoms of thioacetamide\u2010induced hepatic encephalopathy"],"prefix":"10.1002","volume":"75","author":[{"given":"Tomasz","family":"Saran","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wojciech","family":"Hilgier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewa M.","family":"Urba\u0144ska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waldemar A.","family":"Turski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Albrecht","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,12,4]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19980115)51:2<133::AID-JNR1>3.0.CO;2-E"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(84)90320-3"},{"key":"e_1_2_5_4_1","first-page":"465","volume-title":"Biochemical pathology of astrocytes","author":"Albrecht J","year":"1988"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(99)00169-0"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s007020050149"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2000.0752051.x"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0953-816x.2001.01592.x"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-0186(02)00030-X"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4613-0381-7_43"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903210313"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1997.69010290.x"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4684-5952-4_72"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19971101)50:3<457::AID-JNR12>3.0.CO;2-3"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1525-1373.1999.d01-120.x"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510310322"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1994.62010197.x"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19990401)56:1<76::AID-JNR10>3.0.CO;2-Y"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1999.0720643.x"},{"key":"e_1_2_5_20_1","first-page":"899","article-title":"Chronic treatment with ionotropic glutamate receptor antagonist kynurenate affects GABAergic synaptic transmission in rat hippocampal cell cultures","volume":"117","author":"Ivanova SY","year":"2003","journal-title":"Neuroscience"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-0186(03)00041-X"},{"key":"e_1_2_5_22_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00702-002-0770-z","article-title":"Kynurenate production by cultured human astrocytes","volume":"110","author":"Kiss C","year":"2003","journal-title":"J Neural Transm"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.10243"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(03)00579-2"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)52451-6"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02029494"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510240425"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-0186(02)00029-3"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-1007237"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1136(199709)21:1<124::AID-GLIA14>3.0.CO;2-U"},{"key":"e_1_2_5_31_1","first-page":"572","article-title":"Cerebral metabolic and histological effects of thioacetamide\u2010induced liver failure","volume":"265","author":"Peeling J","year":"1993","journal-title":"Am J Physiol"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1990.tb04149.x"},{"key":"e_1_2_5_33_1","first-page":"379","article-title":"Thioacetamide\u2010induced hepatic encephalopathy in the rat. 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