Balter-Seri J, Yuhas Y, Weizman A, Nofech-Mozes Y, Kaminsky E, Ashkenazi S
Felsenstein Medical Research Center, Petah Tiqva, Tel Aviv, Israel.
Infect Immun. 1999 Dec;67(12):6364-8. doi: 10.1128/IAI.67.12.6364-6368.1999.
Convulsions and encephalopathy are frequent complications of childhood shigellosis. We studied the role of nitric oxide (NO) in Shigella-related seizures in an animal model. Pretreatment of mice with Shigella dysenteriae 60R sonicate elevated serum NO levels and enhanced the convulsive response to pentylenetetrazole (PTZ), as indicated by a higher mean convulsion score and a higher number of mice responding with seizures. Treatment of the mice with S-methylisothiourea sulfate (SMT), a potent inhibitor of inducible NO synthase (NOS), prevented the elevation of serum NO levels and concomitantly reduced the enhanced response to PTZ. The mean convulsion scores were 0.7, 0.7, 1.3, and 0.8 for mice treated with saline, saline and SMT, S. dysenteriae 60R sonicate, and S. dysenteriae 60R sonicate with SMT, respectively (P = 0.001 for 60R sonicate versus saline and P = 0.013 for 60R sonicate versus 60R sonicate with SMT). The corresponding seizure rates were 40, 44, 75, and 47% for saline, saline with SMT, S. dysenteriae 60R sonicate, and S. dysenteriae 60R sonicate with SMT, respectively (P = 0.0004 for 60R sonicate versus saline and P = 0.005 for 60R sonicate versus 60R sonicate with SMT). In contrast, injection of N-nitro-L-arginine, a selective inhibitor of constitutive NOS, neither abolished the elevation of serum NO nor attenuated the enhancement of seizures. These findings indicate that NO, induced by S. dysenteriae 60R sonicate, is involved in enhancing the susceptibility to seizures caused by S. dysenteriae.
惊厥和脑病是儿童志贺氏菌病常见的并发症。我们在动物模型中研究了一氧化氮（NO）在志贺氏菌相关癫痫发作中的作用。用痢疾志贺氏菌60R超声裂解物预处理小鼠可提高血清NO水平，并增强对戊四氮（PTZ）的惊厥反应，表现为平均惊厥评分更高以及出现惊厥反应的小鼠数量更多。用强力诱导型一氧化氮合酶（NOS）抑制剂硫酸S-甲基异硫脲（SMT）处理小鼠，可防止血清NO水平升高，并同时降低对PTZ增强的反应。用盐水、盐水和SMT、痢疾志贺氏菌60R超声裂解物、痢疾志贺氏菌60R超声裂解物和SMT处理的小鼠，其平均惊厥评分分别为0.7、0.7、1.3和0.8（60R超声裂解物与盐水相比，P = 0.001；60R超声裂解物与60R超声裂解物加SMT相比，P = 0.013）。相应的癫痫发作率，用盐水、盐水加SMT、痢疾志贺氏菌60R超声裂解物、痢疾志贺氏菌60R超声裂解物加SMT处理的小鼠分别为40%、44%、75%和47%（60R超声裂解物与盐水相比，P = 0.0004；60R超声裂解物与60R超声裂解物加SMT相比，P = 0.005）。相比之下，注射组成型NOS的选择性抑制剂N-硝基-L-精氨酸，既不能消除血清NO的升高，也不能减弱癫痫发作的增强。这些发现表明，痢疾志贺氏菌60R超声裂解物诱导产生的NO参与增强了痢疾志贺氏菌引起的癫痫易感性。
