{"id":"3f0ca549-254e-5580-8416-15625f72d686","stable_key":"46d15d9e-d3b5-544d-ba01-b785aa3e4f42:thiamine-def-thalamic-extracellular-glutamate","predicate":"antagonist-assisted-depletion-increases","statement":"Acute symptomatic rats had thalamic dialysate glutamate of 3.37 versus 0.93 micromolar in controls, with no corresponding cortical increase.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"9ee7413a-869b-59d3-a412-3fb6e9edbce6","mechanism_event_label":"Glutamate accumulated outside cells in a vulnerable region before visible tissue lesions.","subject":{"id":"36b7c3eb-068b-500f-af1c-078829df1ecc","slug":"thiamine","display_name":"Thiamine (vitamin B1)","entity_type_key":"small_molecule"},"object":{"id":"99d76f2a-9f22-5d27-8d03-b75581c5f036","slug":"extracellular-brain-glutamate-concentration","display_name":"Extracellular brain glutamate concentration","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"9ee7413a-869b-59d3-a412-3fb6e9edbce6","stable_key":"46d15d9e-d3b5-544d-ba01-b785aa3e4f42:thiamine-def-thalamic-extracellular-glutamate-event","event_type":"biochemical_relationship","label":"Glutamate accumulated outside cells in a vulnerable region before visible tissue lesions.","description":"Acute symptomatic rats had thalamic dialysate glutamate of 3.37 versus 0.93 micromolar in controls, with no corresponding cortical increase.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"7da684a4-2641-5bc6-93ae-8c6aa384e487","slug":"glutamate","display_name":"L-Glutamate","entity_type_key":"small_molecule"},"role":"measured extracellular transmitter","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"75a7f374-5ae9-5565-9f52-388e627bb492","slug":"pyrithiamine","display_name":"Pyrithiamine","entity_type_key":"small_molecule"},"role":"experimental antagonist","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"36b7c3eb-068b-500f-af1c-078829df1ecc","slug":"thiamine","display_name":"Thiamine (vitamin B1)","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"99d76f2a-9f22-5d27-8d03-b75581c5f036","slug":"extracellular-brain-glutamate-concentration","display_name":"Extracellular brain glutamate concentration","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_location","value_text":"Abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_span","value_text":"precedes the appearance of histological lesions","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Awake freely moving rats with pyrithiamine-induced deficiency; microdialysis of ventral posterior medial thalamus and contralateral frontoparietal cortex, compared with pair-fed controls.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Pyrithiamine-induced deficiency within six hours of loss of righting reflexes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Microdialysis alone cannot assign increased release versus impaired uptake or prove NMDA-mediated cell death. Combined thiamine withdrawal and pyrithiamine exposure; not an estimate for mild dietary insufficiency or a human blood threshold.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Thiamine research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"thiamine","display_name":"Thiamine (vitamin B1)","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Rattus norvegicus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Glutamate accumulated outside cells in a vulnerable region before visible tissue lesions.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[hazell-1993-extracellular-glutamate] Cerebral vulnerability is associated with selective increase in extracellular glutamate concentration in experimental thiamine deficiency (1993). https://pubmed.ncbi.nlm.nih.gov/8103080/ DOI: 10.1111/j.1471-4159.1993.tb03635.x","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Ventral posterior medial thalamus versus frontoparietal cortex","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"2222a4be-ad9a-54c7-bad7-5e6719f0fb8a","evidence_kind":"source_excerpt","locator":"Lines 1141-1153","start_line":1141,"end_line":1153,"excerpt":"### thiamine-def-thalamic-extracellular-glutamate\nAcute symptomatic rats had thalamic dialysate glutamate of 3.37 versus 0.93 micromolar in controls, with no corresponding cortical increase.\nCondition category: nutrient_deficiency\nnutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Glutamate accumulated outside cells in a vulnerable region before visible tissue lesions.\norganism: Rattus norvegicus\ntissue_or_cell_type: Ventral posterior medial thalamus versus frontoparietal cortex\nexperimental_model: Awake freely moving rats with pyrithiamine-induced deficiency; microdialysis of ventral posterior medial thalamus and contralateral frontoparietal cortex, compared with pair-fed controls.\nlimitations: Microdialysis alone cannot assign increased release versus impaired uptake or prove NMDA-mediated cell death. Combined thiamine withdrawal and pyrithiamine exposure; not an estimate for mild dietary insufficiency or a human blood threshold.\nevidence_location: Abstract\nevidence_span: precedes the appearance of histological lesions\nexposure: Pyrithiamine-induced deficiency within six hours of loss of righting reflexes\n[hazell-1993-extracellular-glutamate] Cerebral vulnerability is associated with selective increase in extracellular glutamate concentration in experimental thiamine deficiency (1993). https://pubmed.ncbi.nlm.nih.gov/8103080/ DOI: 10.1111/j.1471-4159.1993.tb03635.x","model_system":"Awake freely moving rats with pyrithiamine-induced deficiency; microdialysis of ventral posterior medial thalamus and contralateral frontoparietal cortex, compared with pair-fed controls.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [hazell-1993-extracellular-glutamate] Cerebral vulnerability is associated with selective increase in extracellular glutamate concentration in experimental thiamine deficiency (1993). https://pubmed.ncbi.nlm.nih.gov/8103080/ DOI: 10.1111/j.1471-4159.1993.tb03635.x","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"158d2c03-ac8c-589f-8270-c468165ae346","stable_key":"import-46d15d9e-d3b5-544d-ba01-b785aa3e4f42","title":"Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"f376512fb3310141315548015b387833e3af45146e73fb73cd02cee20e4ddb9c","revision_id":"53bc5eda-dec8-58cc-a56f-a9eb4ab036ef","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}