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OBJECTIVE To investigate whether the transient augment of cytokine Interleukin 1(IL-1) in hippocampus after febrile seizures initiates molecular cascades to promote epileptogenesis.METHODS Febrile seizures(FS) were induced by exposing SD rat pups(P8-10) to a hyperthermal chamber(44±2)℃ to raise the body temperature with stereotyped behaviors.IL-1 receptor antagonist(IL-1ra) was injected into the hippocampus immediately,24 h,3 d or 7 d after FS.0.3,1,3 and 10 ng/0.4 μl of IL-1 were injected alone in normal rat pups(P8-10).CB1 receptor antagonist SR141716A(ip) was administered 3 d or 7 d after FS induction and IL-1 injection.When the rats were adults,their sensitivity to epilepsy was measured by Maximal electroshock(MES).Expression of CB1 receptors was detected by Western Blotting at postnatal d 15 and 45,respectively.RESULTS IL-1ra administered immediately and 24 h after FS reversed the enhanced susceptibility to MES-induced seizures and upregulated the expression of CB1 receptors.IL-1 alone increased both the susceptibility to seizures and the expression of CB1 receptors till day 15 at all doses,and the dose of 1 ng showed a long-lasting effect(at least for 45 d).CB1 receptor antagonist SR141716A abolished the enhanced susceptibility to seizures.CONCLUSION Our study indicates that augmented levels of IL-1 in the hippocampus after FS might promote epileptogenesis by,at least partly,modulating endocannabinoid signaling.
OBJECTIVE To investigate whether the transient augment of cytokine Interleukin 1 (IL-1) in hippocampus after febrile seizures initiates molecular cascades to promote epileptogenesis. METHODS Febrile seizures (FS) were induced by exposing SD rat pups (P8-10) to a hyperthermal chamber (44 ± 2) ° C to raise the body temperature with stereotyped behaviors. IL-1 receptor antagonist (IL-1ra) was injected into the hippocampus immediately, 24 h, 3 d or 7 days after FS 0.3, 1, 3 and 10 ng / 0.4 μl of IL-1 were injected alone in normal rat pups (P8-10). CB1 receptor antagonist SR141716A (ip) was administered 3 d or 7 days after FS induction and IL-1 injection. their sensitivity to epilepsy was measured by Maximal electroshock (MES). Expression of CB1 receptors was detected by Western Blotting at postnatal d 15 and 45, respectively. RESULTS IL-1ra administered immediately and 24 h after FSH induced susceptibility to MES-induced seizures and upregulated the expression of CB1 receptors. I L-1 alone increased both susceptibility to seizures and the expression of CB1 receptors till day 15 at all doses, and the dose of 1 ng showed a long-lasting effect (at least for 45 days). CB1 receptor antagonist SR141716A abolished the enhanced susceptibility to seizures.CONCLUSION Our study indicates that augmented levels of IL-1 in the hippocampus after FS might promote epileptogenesis by, at least partly, modulating endocannabinoid signaling.