title: Depletion of brain histamine produces regionally selective protection against thiamine deficiency-induced lesions in the rat.
abstract: Breakdown of the blood brain barrier and the subsequent accumulation of free radicals, lactate, and glutamate appear to be the immediate causes of thiamine deficiency (TD)-induced damage to thalamus. The mechanisms triggering these events are unknown but recent evidence suggests an important role of histamine. We therefore studied the effects of histamine depletion on thalamic lesions in the pyrithiamine-induced thiamine deficient (PTD) rat. Chronic intracerebroventricular (i.c.v., 7 days) infusion of alpha-fluoromethylhistidine (FMH), combined with bilateral ibotenate destruction of the histamine-containing neurons in the tuberomammillary (TM) nucleus and bolus i.c.v. infusion of 48/80, a potent mast cell degranulating agent, was used to deplete brain histamine levels. PTD rats receiving combined FMH + 48/80 + TM lesions developed acute neurological symptoms, including spontaneous seizures, approximately 1 day earlier than PTD rats treated with i.c.v. infusion of vehicle and sham lesions of the TM. When examined 1 week after restoration of thiamine, the PTD vehicle + sham lesion animals contained severe neuronal loss and gliosis in midline, intralaminar, ventral, lateral, and posterior nuclei. PTD animals treated with FMH + 48/80 + TM lesions had little evidence of neuronal loss or microglial proliferation in thalamus except in the gelatinosus and anteroventral nuclei, in which there was complete neuronal loss. These data demonstrate a significant and regionally selective role of histamine in the development of thalamic lesions in a rat model of Wernicke's encephalopathy. Furthermore, these data suggest either a dissociation between seizures and thalamic lesions or a significant role of histamine in seizure-related damage to the thalamus.
mesh_terms: D000818:Animals; D000963:Antimetabolites; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000502:physiology*; D004791:Enzyme Inhibitors; D006632:Histamine / Q000502:physiology*; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors; D007026:Hypothalamic Area, Lateral / Q000502:physiology; D007276:Injections, Intraventricular; D008297:Male; D008762:Methylhistidines; D020258:Neurotoxicity Syndromes / Q000523:psychology; D011745:Pyrithiamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013787:Thalamic Nuclei / Q000473:pathology; D013788:Thalamus / Q000473:pathology; D013832:Thiamine Deficiency / Q000139:chemically induced / Q000473:pathology*
chemical_list: D000963:Antimetabolites; D004791:Enzyme Inhibitors; D008762:Methylhistidines; D011745:Pyrithiamine; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D006640:Histidine Decarboxylase