Objective: To examine whether hyperthermia aggravates cerebral injury in acute ischemia by an excitotoxic mechanism, we studied the relationship between body temperature on admission and CSF concentrations of neuroexcitatory amino acids in 128 patients with acute ischemic stroke of less than 24 h duration. Methods: Stroke worsening was defined as the percent change between the Canadian Stroke Scale (CSS) at 48 h and the CSS on admission. Infarct volume was measured on days 4–7 on cranial computed tomography. Excitatory amino acids were analyzed using HPLC. Results: Glutamate concentration [median (min.-max.)] was 11 (2–19) µmol/l in hyperthermic patients (body temperature >37.5°C) and 5 (2–22) µmol/l in normothermic patients (p < 0.0001). Glycine concentration in hyperthermic and normothermic patients was 16 (3–21) µmol/l and 9 (3–50) µmol/l, respectively (p < 0.0001). Glutamate was significantly higher in patients with hyperthermia only during the first 12 h after the onset of symptoms. The CSF concentrations of glutamate (r = 0.52; p < 0.0001) and glycine (r = 0.62; p < 0.0001) correlated with body temperature. Body temperature was significantly related to stroke worsening and infarct size, but this effect was dependent on the glutamate effect. Conclusion: Glutamate and glycine release during the acute phase of cerebral ischemia could be responsible for the increased brain damage in hyperthermia.

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