Central Control of Neurogenic Fever Following Subarachnoid Hemorrhage

Subarachnoid hemorrhage (SAH) is a devastating form of stroke that is associated with autonomic dysfunction including neurogenic fever (NF) that contributes to an increase in mortality and worse outcomes. Drugs that inhibit cyclooxygenase (COX) are generally ineffective in treating NF which suggesting a different central mediator for the generation of NF than prostaglandins. The aim of this work was to determine in a rat model of SAH if (1) the generation of NF requires the same central thermogenic control and (2) the same thermogenic organs, as that required for the generation of PGE2 mediated fever. In urethane chloralose-anesthetized Wistar rats direct injection of blood into the subarachnoid space evoked an increase of brown adipose tissue sympathetic nerve activity (BAT SNA) and thermogenesis leading to a rapid increase in core temperature. Inhibition of central regions important for cold-evoked and PGE2-mediated thermogenesis, such as the dorsal medial hypothalamus and medullary raphe pallidus, promptly blocked the NF response. However the use of a COX inhibitor to prevent the production of PGE2, failed to completely inhibit NF. We demonstrate for the first time that NF following SAH requires the same central neuronal thermoregulatory circuit and thermogenic organs involved in the generation of PGE2 mediated fever. A significant component of NF appears to be dependent on a different trigger than PGE2. Merit Award Department of Veterans Affairs