The influence of kainic acid on core temperature and cytokine levels in the brain.
Excitotoxic brain injury is associated with hyperthermia, and there are data showing beneficial effects of hypothermia on neurodegeneration and that hyperthermia facilitates the neurodegeneration. Cytokines are inflammatory proteins that seem to be involved in the neuroinflammation associated with epilepsy. Core temperature changes caused by the epileptogenic glutamate analogue kainic acid (KA) were investigated in relation to changes in levels of the pro-inflammatory cytokines interleukin-1beta (IL-1beta) and interleukin-6 (IL-6), and the endogenous interleukin-1 receptor antagonist (IL-1ra). The temperature was measured every 10 min during the first hour, and at 90 and 120 min, and hourly until 8 h after KA-injection (10 mg/kg). The cytokines were measured in the hypothalamus, a site of temperature regulation, and in hippocampus, cerebellum, and frontal cortex. KA induced a brief hypothermia followed by hyperthermia. IL-1beta levels were increased after KA-administration in all brain regions examined and, excepting hippocampus, returned to baseline levels at 24 h. The hippocampal IL-1ra levels were significantly increased at 24 h, whereas no changes in IL-6 levels were observed. The changes in IL-1beta levels and in ratios between the levels of the three cytokines, may account for some of the temperature changes and the behavioural manifestations induced by KA.
Oprica
Mircea
M
Department of Neurobiology, Care Sciences and Society, Division of Neurodegeneration and Neuroinflammation, Karolinska Institutet, Novum, SE-141 86 Stockholm, Sweden. Mircea.Oprica@ki.se
Spulber
Stefan D
SD
Aronsson
Asa Forslin
AF
Post
Claes
C
Winblad
Bengt
B
Schultzberg
Marianne
M
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D016207:Cytokines; D018690:Excitatory Amino Acid Agonists; D007608:Kainic Acid