Tetramethylpyrazine decreases hypothalamic glutamate, hydroxyl radicals and prostaglandin-E2 and has antipyretic effects

We studied the effects of tetramethylpyrazine (TMP) on the fever, increased plasma levels of tumor necrosis factor-alpha (TNF-alpha) and increased hypothalamic levels of glutamate, hydroxyl radicals and prostaglandin-E-2 (PGE(2)) induced by lipopolysaccharide (LPS). The microdialysis probes were stereotaxically and chronically implanted into the hypothalamus of rabbit brain for determining extracellular levels of glutamate, hydroxyl radials, and PGE(2). In addition, both the body core temperature and plasma levels of TNF-alpha were measured. All the body core temperature, plasma levels of TNF-alpha, and hypothalamic levels of glutamate, hydroxyl radicals, and PGE(2) were up-graded by an intravenous dose of LPS (2 mu g/kg). Pretreatment with intravenous TMP (10-40 mg/kg) or intracerebroventricular TMP (130 mu g in 20 mu l per animal) 1 h before LPS administration significantly attenuated the LPS-induced fever as well as the increased hypothalamic levels of glutamate, hydroxyl radicals, and PGE(2). LPS-induced fever could also be attenuated by intravenous or intracerebroventricular TMP 1 h after LPS injection. TMP preconditioning may cause its antipyretic action by reducing plasma levels of TNF-alpha as well as hypothalamic levels of glutamate, hydroxyl radicals, and PGE(2) in rabbits.