Developmental and sex differences in tetramethylenedisulfotetramine (TMDT)-induced syndrome in rats.
Developmental and sex differences in tetramethylenedisulfotetramine (TMDT)-induced syndrome in rats.
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DOI：
10.1002/dneu.22582
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发表时间：
2018-04
影响因子：
3
通讯作者：
Shakarjian MP
中科院分区：
文献类型：
--
作者：
Lauková M;Velíšková J;Velíšek L;Shakarjian MP
四亚甲基二磺基四胺（TMDT）是一种合成的神经毒性灭鼠剂，被认为是一种化学威胁剂。中毒症状包括癫痫发作导致癫痫持续状态和死亡。虽然儿童和妇女往往是受害者，但没有研究调查TMDT对发育中的个人或女性的神经毒性影响。因此，我们进行了这样的调查，在发展中的Sprague-Dawley大鼠的两种性别，以确定潜在的年龄或性别依赖的脆弱性TMDT暴露。皮下注射被选为TMDT暴露的首选途径。EEG记录证实了在出生后第15天（P15）和成年大鼠中观察到的癫痫发作活动。此外，P15大鼠表现出更大的敏感性TMDT比产后25天或成年动物。与男性相比，女性的癫痫发作通常更严重。桶旋转伴随惊厥P25和成人，但在P15大鼠稀疏。成年人发生滚桶的频率低于P25人群。神经元细胞死亡不存在于24小时TMDT幸存者在任何年龄或性别测试。TMDT暴露后7天用氟乙烯进行的癫痫再激发显示，与注射溶剂的对照组相比，P15和成年幸存者的首次阵挛性癫痫发作的潜伏期更长，但进展更快。最后，最年轻的年龄组是最容易受到TMDT诱导的毒性的人群。女性似乎比男性更脆弱。TMDT暴露促进幸存者的癫痫发作扩散和进展。这些发现将有助于建立针对TMDT暴露个体的性别和年龄特异性治疗策略。
Tetramethylenedisulfotetramine (TMDT) is a synthetic neurotoxic rodenticide considered a chemical threat agent. Symptoms of intoxication include seizures leading to status epilepticus and death. While children and women have been often the victims, no studies exist investigating the neurotoxic effects of TMDT in developing individuals or females. Thus, we performed such an investigation in developing Sprague-Dawley rats of both sexes in order to identify potential age- or sex-dependent vulnerability to TMDT exposure. Subcutaneous injection was chosen as the preferred route of TMDT exposure. EEG recordings confirmed the seizure activity observed in both postnatal day 15 (P15) and adult rats. Additionally, P15 rats displayed greater sensitivity to TMDT than postnanatal day 25 or adult animals. Seizures were generally more severe in females compared to males. Barrel rotations accompanied convulsions in P25 and adult, but sparsely in P15 rats. Adults developed barrel rolling less frequently than P25 population. Neuronal cell death was not present in 24-hr TMDT survivors at any age or sex tested. A seizure rechallenge with flurothyl 7 days following TMDT exposure demonstrated longer latencies to the first clonic seizure but a faster progression into the tonic-clonic seizure in P15 and adult survivors as compared to their vehicle-injected counterparts. In conclusion, the youngest age group represents the most vulnerable population to the TMDT-induced toxidrome. Females appear to be more vulnerable than males. TMDT exposure promotes seizure spread and progression in survivors. These findings will help to establish sex- and age-specific treatment strategies for TMDT-exposed individuals.
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影响因子：
3.6
作者：
CORDA, MG;ORLANDI, M;GIORGI, O
通讯作者：
GIORGI, O
影响因子：
3.6
作者：
MARRANNES, R;WAUQUIER, A
通讯作者：
WAUQUIER, A
DOI：
10.1081/clt-120026523
发表时间：
2003-01-01
期刊：
JOURNAL OF TOXICOLOGY-CLINICAL TOXICOLOGY
影响因子：
--
作者：
Barrueto, F;Furdyna, PM;Nelson, LS
通讯作者：
Nelson, LS
影响因子：
3.3
作者：
Deng, Xuejun;Li, Gang;Sun, Shenggang
通讯作者：
Sun, Shenggang
影响因子：
2.2
作者：
Covolan, L;Mello, LEAM
通讯作者：
Mello, LEAM