Cortical spreading depression blocks prostaglandin E1 and endotoxin fever in rats

We have tested the hypothesis that the cortex may play a role in the development of fever. Male Sprague-Dawley rats equipped with AM transmitters for telemetric measurement of body temperature were given intracerebroventricular prostaglandin E1 (PGE1), corticotropin-releasing hormone (CRH), or intravenous E. coli endotoxin. Application of cotton pellets soaked with 3.3 M KCl to the frontal cortex (to induce spreading depression) significantly reduced fevers to PGE1 and endotoxin when compared with fever magnitude with 0.9% NaCl application to the cortex. Neither CRH-induced hyperthermia nor normal body temperatures were altered by the spreading depression. Our results reveal a novel action of spreading depression on thermoregulatory function and indicate cortical involvement in the development of fever.