The Effects of Nimodipine and Intracisternal Urokinase on the Content of Leukotrience C4 in the Brain Tissue after Experimental Subarachnoid Hemorrhage in Rats

Lee, Sun Hee; Yim, Man Bin; Kim, Sang Youl; Lee, Jang Chul; Son, Eun Ik; Kim, Dong Won; Kim, In Hong; Lee, In Kyu

Abstract

To find out whether early lysis of subarachnoid blood clot with intracisternal urokinase as well as intraperitoneal nimodipine prevents or decrease the breakdown of arachidonic acid(AA) of the brain after subarachnoid hemorrhage(SAH), we have investigated the levels of leukotrience(LT) C4, the metabolite of the lipooxygenase pathway of the AA metabolism, in the brain tissue after experimental SAH in rats. The experimental SAH was induced by an intracisternal autologous blood injection through the catheter which was inserted into the cisterna magna. Experimental animals were assigned to one of four groups as follows. The control group(I) was that intracisternal saline irrigation was done after SAH induction. The second group(II) was treated with an injection of nimodipine(4 times per a day of 1.2 mg/Kg until sacrificed) intraperitoneally after SAH induction, the third group(III) was tried with an intracisternal urokinase irrigation(3 times per a day of 0.1 ml, 1 ml : 20,000 unit urokinase, until sacrificed) and the fourth group(IV) was treated with intraperitoneal nimodipine and intracisternal urokinase(same regimen as above). Average levels of LT C4in each group was determined at 24 hours(subgroup a), 48 hours(subgroup b), 72 hours(subgroup c) after the induction of SAH by the radioimmunoassay method. The result showed that average levels of LT C4was significantly enhanced in the brain tissue at 48 hours after SAH induction in control group(group Ia vs. IB vs. Ic : 43.85+/-15.62 vs. 184.32+/-27.46 vs. 39.29+/-12.79 pg/ml, respectively. group Ia vs. Ib vs. Ic ; p<0.01) and was decreased by intraperitoneal nimodipine, intracisternal urokinase or combination of both at 48 hours after SAH induction (group Ib vs. IIb vs. IIIb vs. IVb : 184.32+/-27.46 vs. 41.99+/-5.94 vs. 37.68+/-10.4 vs.37.38+/-9.27 pg/ml, respectively group Ib vs. IIb vs. IIIb, and IVb ; p<0.05). However, there was no significant differences among the second, the third and the fourth group(group IIa vs. IIIa vs. IVa, group IIb vs. IIIb vs. IVb and group IIc vs. IIIc vs. IVc : 41.07+/-7.06 vs. 37.97+/-4.48 vs. 31.84+/-6.07 pg/ml, 41.99+/-5.94 vs. 37.68+/-10.43 vs. 37.38+/-9.27 pg/mi and 36.41+/-6.76 vs. 37.98+/-3.45 vs. 35.59+/-8.37 pg/ml, respectively). We concluded that the early lysis of subarachnoid blood clot with intracisternal urokinase had some benefits against the damage of neurons in the early period after SAH as much as intraperitoneal injection of nimodipine. However, the benefit of the combined treatment with intraperitoneal nimodipine and intracisternal urokinase, compared to intraperioneal nimodipine or intracisternal urokinase alone, has not been cleary established.