Changes in CSF composition during heat stress and fever in conscious rabbits

Elevation of brain temperature after stroke can lead to severe brain injury and even a moderate hyperthermia correlates with increased nervous damage. The role of endogenous cryogens in the pathways that down-regulate body temperature are of overwhelming interest in view of their effectiveness in protecting brain from such damage. The aim of the present work was to study whether heat stress (HS) or fever generates brain homeostatic responses aimed at counteracting the resulting rise in body temperature. Conscious rabbits, with cannulas chronically implanted in the cisterna magna and lateral ventricle, underwent HS (50 min, 40 degrees C) or were injected with 25 ng of endogenous pyrogen IL-1beta, while cerebrospinal fluid (CSF) levels of amino acids involved in central mechanisms of thermoregulation like taurine, GABA, aspartate and glutamate were monitored. The concentrations of some CSF cations (Na(+), K(+), Mg(2+) and Ca(2+)) were also determined in view of their purported role (sodium and calcium in particular) in establishing the thermal set point within the hypothalamus. Results show that during HS-induced hyperthermia, CSF taurine and GABA levels were significantly increased. On the contrary, IL-1beta caused an increase in CSF taurine and, concurrently, a decrease in CSF GABA. Aspartate and glutamate did not change in both conditions. Furthermore, among CSF cations, only calcium and sodium underwent changes. In particular, calcium content increased both in HS- and febrile-animals, while CSF sodium decreased significantly only under IL-1beta-injected treatment. In conclusion, GABA and taurine contribute as endogenous cryogens in a different fashion to the central mechanisms, which regulate dissipation of body heat in hyperthermia or heat production in fever, possibly in coordination with extracellular calcium and sodium.