Involvement of brain glutamate release in pyrogenic fever

Area of Science:

• Neuroscience
• Physiology
• Pharmacology

Background:

• The precise mechanisms underlying fever genesis remain incompletely understood.
• The role of glutamate release in the organum vasculosum laminae terminalis (OVLT) during pyrogenic fever is unclear.

Purpose of the Study:

• To investigate the changes in OVLT glutamate concentrations during fever induced by staphylococcal enterotoxin A (SEA) in rabbits.
• To determine the involvement of glutamatergic pathways in the OVLT in fever development.

Main Methods:

• Microdialysis was used to measure extracellular glutamate concentrations in the OVLT of unanesthetized rabbits.
• Colonic temperatures were monitored simultaneously with glutamate levels during systemic or intra-OVLT administration of SEA, NMDA receptor blockers (MK801, ketamine), or saline.
• High-pressure liquid chromatography with a fluorescence detector was employed for glutamate quantification.

Main Results:

• Systemic SEA administration increased both OVLT glutamate concentrations and colonic temperatures, with glutamate levels rising slightly before body temperature.
• Pretreatment or posttreatment with MK801 or ketamine significantly attenuated SEA-induced glutamate release and fever.
• Direct injection of SEA or glutamate into the OVLT mimicked SEA-induced fever, which was also attenuated by NMDA receptor blockers.

Conclusions:

• Glutamatergic pathways within the OVLT region are implicated in the genesis of pyrogenic fever.
• NMDA receptor antagonists effectively reduce fever by inhibiting glutamate release in the OVLT.