An experimental model of acute encephalopathy after total body irradiation in the rat: effect of liposome-entrapped Cu/Zn superoxide dismutase.
OBJECTIVE
To develop an experimental model of acute encephalopathy following total body irradiation in rats and to define the therapeutic effect of liposome-entrapped Cu/Zn superoxide dismutase.


METHODS
A total of 120 4-month-old rats received 4.5 Gy total body irradiation (TBI) while 120 rats received sham irradiation. A behavioral study based on a conditioning test of negative reinforcement, the one-way avoidance test, was performed 5 hours before irradiation and repeated the following days. Subcutaneous treatment was started 1 hour after irradiation and repeated daily for 2 weeks. In both the irradiated and sham group, three subgroups were defined according to the treatment received: liposome-entrapped Cu/Zn superoxide dismutase (0.5 mg/kg), liposomes only, normal saline.


RESULTS
This work comprised two consecutive studies. In study A (90 rats) the one-way avoidance test was administered daily from day 0 to day 4 with a recall session at day 14. In study B (validation phase in 150 rats) the behavioral test was performed only from day 0 to day 6. Before irradiation, all rats showed a similar behavioral response. Study A (6 groups of 15 rats): Following TBI, irradiated rats treated with liposomes only or saline demonstrated a significant delay in learning the one-way avoidance test in comparison with sham-irradiated rats (0.05 < p <0.001 depending upon the day of evaluation and the subgroup type). In contrast, irradiated rats treated with liposome-entrapped Cu/Zn superoxide dismutase did not differ from sham-irradiated rats. Study B (6 groups of 25 rats): The results were the same as those in study A, demonstrating a significant delay in the learning of the test in the liposome and saline-treated irradiated rats in comparison with sham-irradiated rats (0.02 < p < 0.001). The irradiated rats, treated with liposome-entrapped Cu/Zn superoxide dismutase did not differ from the sham-irradiated controls.


CONCLUSIONS
This study indicates that a relatively low dose of total body irradiation induces a substantial acute learning dysfunction in the rat. This effect is prevented by the administration of liposome-entrapped Cu/Zn superoxide dismutase.
Lamproglou
I
I
Laboratoire de Biophysique, Faculté de Médecine Xavier Bichat, Paris, France.
Magdelenat
H
H
Boisserie
G
G
Baillet
F
F
Mayo
W
W
Fessi
H
H
Puisieux
F
F
Perderau
B
B
Colas-Linhart
N
N
Delattre
J Y
JY
D000818:Animals; D001362:Avoidance Learning / Q000528:radiation effects*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology*; D003213:Conditioning, Psychological; D004195:Disease Models, Animal; D004337:Drug Carriers; D008081:Liposomes; D008297:Male; D011833:Radiation Injuries, Experimental / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000627:therapeutic use*; D014916:Whole-Body Irradiation / Q000009:adverse effects*
D004337:Drug Carriers; D008081:Liposomes; D013482:Superoxide Dismutase