[Reproduction of a murine model of hyperthermic treatment].

ABSTRACT

OBJECTIVE: To find out the most suitable conditions for a whole body hyperthermia (WBH) model and the influence of these conditions on the blood brain barrier (BBB) disruption and brain edema in rats. METHODS: Forty male Sprague-Dawley (SD) rats were randomly assigned to four groups (n=10 in each group) control group, group A, group B and group C. After anesthesia with pentobarbital, rats were subjected to femoral artery and vein cannulation. Rats of control group were housed at a controlled room temperature (25-26 degrees C) for 4 hours. Rats of group A, group B and group C were exposed to WBH in a biological oxygen supply heated container (relative humidity 65%, wind velocity 25 cm/s) maintained at 34, 36 and 38 degrees C for 3 hours, respectively. Then the rats were removed from the heated container and their body temperature was cooled down for 1 hour. During heating, rectal temperature, heart rate (HR), mean arterial pressure (MAP), pH, partial pressure of oxygen in artery (PaO(2)), partial pressure of carbon dioxide in artery (PaCO(2)), the dosage of anesthetic, and the mortality rate in each group were recorded. Evans blue (EB) was administered into the femoral vein and allowed to circulate for 5 minutes. At the end of the experiment, the animals were perfused with 0.9% saline and heparin through the heart, and the brain was harvested for the examination of BBB permeability, water content and morphological alterations in brain tissues and neurons. RESULTS: The total dosage of pentobarbital was not significantly different among all groups. After WBH for 3 hours, the average rectal temperature was higher than rats without WBH, and the mortality rate was 0, 10%, 10% and 40% in groups control, A, B, C, respectively. HR of groups A, B and C were significantly higher than those of control group; MAP, pH of group A, B and C were significantly lower than those of control group (all P<0.05). Compared to that of control group, water content of the brain and permeability of EB in groups A, B and C were significantly increased (P<0.05 or P<0.01), but there was no marked difference on PaO(2), PaCO(2) and haematocrit (HCT) among groups A, B and C. Morphological investigation showed that there were different degrees of structural changes in brain tissue in groups A, B and C under light microscopy. Under transmission election microscopy, the structure of nerve cells and BBB in group B and group C showed moderate to profound alterations, but there were no changes in group A. CONCLUSION: Rats housed in a biological oxygen supply heat container with the temperature maintained at 36 degrees C for 3 hours could establish an ideal WBH model with notable BBB breakdown, moderate brain edema, and histological changes in brain.