An extensive clinical literature indicates that cerebral injury due to head trauma, vascular lesions and certain neurosurgical procedures and cerebral disease states is not uncommonly followed by hyperpyrexia. These so-called neurogenic or cerebrogenic pyrexias are sometimes life threatening in themselves and in all cases complicate the management of the brain injured patient. Our understanding of the pathological processes responsible for the generation of cerebrogenic pyrexias is rudimentary. The general goal of the proposed research is to provide basic information in this regard by studying in cats the effects of several types of brain injury which cause pyrexia in man. Although the mechanism of pyrexia caused by pontine lesions will be examined, the studies will focus on pyrexias associated with unilateral or bilateral injury to the anterior hypothalamic/preoptic (AH/PPO) region and with unilateral injury to other parts of he hypothalamus and to certain nearby structures (""""""""extra-AH/PO"""""""" structures). At present, pyrexia following these types of injuries is usually attributed to a thermoregulatory dysfunction caused by lesion-induced disruption of the """"""""hard-wiring"""""""" of the system. However, we believe that in many cases these lesions cause pyrexia by releasing pyrogenic cyclo-oxygenase products which then act on surviving AH/PO tissue to cause a fever-like pyrexia. To test this general hypothesis we will examine the effect of the cyclo-oxygenase inhibitor, indomethacin, on pyrexias induced by bilateral and unilateral electrolytic lesions of the AH/PO region and by unilateral lesions of extra-AH/PO structures. We will also examine the effect of unilateral lesions of extra-AH/PO structures. We will also examine the effect of unilateral AH/PO and extra-AH/PO lesions on the concentration of cyclo-oxygenase products in the AH/PO region and/or in third ventricular CSF. In addition, the effect of an inhibitor of the transport of prostaglandins from brain tissue to blood (probenecid) on pyrexia evoked by unilateral AH/PO lesions will be investigated. Finally, we will evaluate the thermoregulatory characteristics of pyrexias elicited by unilateral and bilateral AH/PO lesions to see if they are commensurate with a prostaglandin model of mediation.
