Neuregulin-1 is neuroprotective in a rat model of organophosphate-induced delayed neuronal injury.
Neuregulin-1 is neuroprotective in a rat model of organophosphate-induced delayed neuronal injury.
复制标题
DOI：
10.1016/j.taap.2012.05.001
复制
发表时间：
2012-07-15
影响因子：
3.8
通讯作者：
Ford, Byron D.
中科院分区：
文献类型：
--
作者：
Li, Yonggang;Lein, Pamela J.;Liu, Cuimei;Bruun, Donald A.;Giulivi, Cecilia;Ford, Gregory D.;Tewolde, Teclemichael;Ross-Inta, Catherine;Ford, Byron D.
关键词：
目前针对有机磷（OP）神经毒剂的医学对策在降低死亡率方面是有效的，但不能充分保护CNS免受迟发性脑损伤和持续性神经症状的影响。在这项研究中，我们研究了神经调节蛋白-1（NRG-1）在OP二异丙基氟磷酸盐（DFP）急性中毒后对迟发性神经元细胞死亡的保护作用。成年雄性Sprague道利大鼠用吡啶斯的明（0.1 mg/kg BW，i.m.）和阿托品硝酸甲酯（20 mg/kg BW，i.m.）在DFP（9 mg/kg BW，i.p.）中毒，以增加存活率和减少胆碱能毒性的外周体征，但不能预防DFP诱导的癫痫发作或迟发性神经元损伤。用NRG-1预处理不能防止暴露于DFP的大鼠癫痫发作。然而，通过用NRG-1亚型NRG-EGF（3.2 μg/kg BW，i.a.）或NRG-GGF 2（48 μg/kg BW，i.a.）如通过在DFP注射后24小时在多个脑区域中的FluroJade-B标记所确定的。NRG-1还阻断了DFP中毒大鼠脑中细胞凋亡和氧化应激介导的蛋白质损伤。在DFP注射后1小时施用NRG-1类似地提供了针对迟发性神经元损伤的显著神经保护。这些发现将NRG-1确定为当前医学对策的有希望的辅助疗法，用于增强对急性OP中毒的神经保护。
Current medical countermeasures against organophosphate (OP) nerve agents are effective in reducing mortality, but do not sufficiently protect the CNS from delayed brain damage and persistent neurological symptoms. In this study, we examined the efficacy of neuregulin-1 (NRG-1) in protecting against delayed neuronal cell death following acute intoxication with the OP diisopropylfluorophosphate (DFP). Adult male Sprague Dawley rats were pretreated with pyridostigmine (0.1 mg/kg BW, i.m.) and atropine methylnitrate (20 mg/kg BW, i.m.) prior to DFP (9 mg/kg BW, i.p.) intoxication to increase survival and reduce peripheral signs of cholinergic toxicity but not prevent DFP-induced seizures or delayed neuronal injury. Pretreatment with NRG-1 did not protect against seizures in rats exposed to DFP. However, neuronal injury was significantly reduced in most brain regions by pretreatment with NRG-1 isoforms NRG-EGF (3.2 μg/kg BW, i.a) or NRG-GGF2 (48 μg/kg BW, i.a.) as determined by FluroJade-B labeling in multiple brain regions at 24 h post-DFP injection. NRG-1 also blocked apoptosis and oxidative stress-mediated protein damage in the brains of DFP-intoxicated rats. Administration of NRG-1 at 1 h after DFP injection similarly provided significant neuroprotection against delayed neuronal injury. These findings identify NRG-1 as a promising adjuvant therapy to current medical countermeasures for enhancing neuroprotection against acute OP intoxication.
登录
查看更多内容
影响因子：
5.8
作者：
ELLMAN, GL;COURTNEY, KD;FEATHERSTONE, RM
通讯作者：
FEATHERSTONE, RM
影响因子：
4.5
作者：
Kadriu, Bashkim;Guidotti, Alessandro;Auta, James
通讯作者：
Auta, James
影响因子：
56.9
作者：
HOLMES, WE;SLIWKOWSKI, MX;VANDLEN, RL
通讯作者：
VANDLEN, RL
影响因子：
2.9
作者：
Croslan, DaJoie R.;Schoell, Matthew C.;Ford, Byron D.
通讯作者：
Ford, Byron D.
影响因子：
2.9
作者：
MCDONOUGH, JH;MCLEOD, CG;NIPWODA, MT
通讯作者：
NIPWODA, MT