A. In neuroprotective model, immediately after hypoxic-ischemic (HI) insult (at 0 h), the rectal temperature was significantly increased only in the vehicle group than in the sham group, whereas 2h later the rectal temperature was significantly decreased in pretreated by 5mg/kg/day E4 and 1.6mg/kg/day P4 with/without 136ng/kg/day E2 groups compared to the sham group. 4h later no significant difference was observed among the study groups. B. In therapeutic model, between the study groups immediately after HI insult no significant differences were detected, whereas 2h later groups treated by combination of 5mg/kg/day or 10mg/kg/day E4 with 16mg/kg/day P4 plus 136ng/kg/day E2 had significantly decreased rectal temperature than the vehicle group or the groups treated by the same doses of E4 with 1.6mg/kg/day P4 and E2. Moreover, combination of 10mg/kg/day E4 with 16mg/kg/day P4 and 136ng/kg/day E2 significantly downregulated the rectal temperature compared to the sham group, or the group treated by 10mg/kg/day E4 and 16mg/kg/day P4 (Figure 2B). Also, the groups treated by 10mg/kg/day E4 alone or combined with 1.6mg/kg/day P4 had significantly decreased rectal temperature compared to the group treated by 10mg/kg/day E4 with 1.6mg/kg/day P4 and 136ng/kg/day E2. At 4h after HI event, animals treated by 5mg/kg/day or 10mg/kg/day E4 and 136ng/kg/day E2 with/without 16mg/kg/day P4 had significantly decreased rectal temperature along with the sham group compared to animals treated by single doses of E4 (Figure 2B). The same pattern was observed between groups treated by 10mg/kg/day E4 with 1.6mg/kg/day P4 and 136ng/kg/day E2, and the group treated by E4 alone. Treatment by 5mg/kg/day E4 with 16mg/kg/day P4 and 136ng/kg/day E2 significantly decreased the rectal temperature than the treatment by the same combination of compounds with 1.6mg/kg/day P4 (Figure 2B). All measurements are expressed as mean±SEM.*p ≤ 0.05.