Effect Of L-Nitroarginine And L-Arginine On Kainic Acid-Induced Seizures In Rats And Morphological, Anatomical, And Biochemical Alterations Of Astrocytes In The Hippocampal Formation

To further determine whether or not nitric oxide mediator (s) is involved in epilepsy and address the cellular and biochemical mechanisms, we evaluated the effect of L-nitroarginine (50mg/kg b. w. , i. p. , twice daily for 9 times) or L-arginime (10, 40, or 160mg/kg b. w. , i. p. , twice daily for 9 times) on kainic acid (10mg/kg b. w. , i. p. ) -induced seizures in young adult male rats and the corresponding changes in Fos-, IL-6-, Hsp 72/73-, GFAP-, and OX42-im-munoreactivity (ir) in the most affected brain region, the hippocampal formation. It was found that kainic acid caused in almost all of the animals a series of stereotype behavorial changes, and corresponding rapid increases in Fos-, IL-6-, GFAP-, and OX42-ir and NO₂^-/NO₃^- concentration in the hippocampal formation. Hsp72/73-ir and the mRNA of inducible nitric oxide synthase were also found increased several hours to days later. Under basal conditions, the chronic treatment of L-nitroarginine or L-arginine caused no apparent behavioral changes. However, the chronic pretreatment of L-nitroarginine so dramatically promoted and enhanced the kainic acid-induced behavioral seizures that almost all of the animals died at about 3 hours after kainic acid injection. In contrast, the chronic pretreatment of L-arginine at 40 or 160mg/kg b. w. dose markedly...