Sodium sulfide prevents water diffusion abnormality in the brain and improves long term outcome after cardiac arrest in mice.
Sodium sulfide prevents water diffusion abnormality in the brain and improves long term outcome after cardiac arrest in mice.
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DOI：
10.1016/j.resuscitation.2012.02.020
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发表时间：
2012-10
期刊：
影响因子：
6.5
通讯作者：
Ichinose F
中科院分区：
文献类型：
--
作者：
Kida K;Minamishima S;Wang H;Ren J;Yigitkanli K;Nozari A;Mandeville JB;Liu PK;Liu CH;Ichinose F
心脏骤停（CA）是世界范围内死亡的主要原因之一。先前我们证明了硫化氢（H2S）供体硫化钠（Na2S）在小鼠CA和心肺复苏（CPR）后24小时显著改善神经预后和生存率。在本研究中，我们试图阐明Na2S神经保护作用的机制及其对小鼠CA/CPR后长期存活的影响。成年雄性小鼠在37°C下进行钾诱导的CA 7.5 min，然后在胸部按压和机械通气的情况下进行心肺复苏术。小鼠在心肺复苏术前1分钟给予Na2S （0.55 mg/kg静脉注射）或载药。接受CA/CPR和载药治疗的小鼠10天存活率较低（4/12），神经功能下降。CA/CPR后24小时的高强度弥散加权成像（DWI）显示，心脏骤停和心肺复苏术诱导大脑脆弱区域的异常水扩散。高强度DWI的程度与基质金属蛋白酶9 （MMP-9）激活、更差的神经预后以及CA/CPR后10天的低生存率相关。Na2S可阻止CA/CPR后异常水扩散和MMP-9活化的发生，显著改善CA/CPR后神经功能和长期生存（9/12，P<0.05）。这些结果表明，心肺复苏前1分钟给予Na2S可能通过在复苏后早期抑制MMP-9的激活来阻止脑内水扩散异常，从而改善CA/CPR后10天的神经功能和存活率。
Sudden cardiac arrest (CA) is one of the leading causes of death worldwide. Previously we demonstrated that administration of sodium sulfide (Na2S), a hydrogen sulfide (H2S) donor, markedly improved the neurological outcome and survival rate at 24h after CA and cardiopulmonary resuscitation (CPR) in mice. In this study, we sought to elucidate the mechanism responsible for the neuroprotective effects of Na2S and its impact on the long-term survival after CA/CPR in mice. Adult male mice were subjected to potassium-induced CA for 7.5 min at 37°C whereupon CPR was performed with chest compression and mechanical ventilation. Mice received Na2S (0.55 mg/kg i.v.) or vehicle 1 min before CPR. Mice that were subjected to CA/CPR and received vehicle exhibited a poor 10-day survival rate (4/12) and depressed neurological function. Cardiac arrest and CPR induced abnormal water diffusion in the vulnerable regions of the brain, as demonstrated by hyperintense diffusion-weighted imaging (DWI) 24h after CA/CPR. Extent of hyperintense DWI was associated with matrix metalloproteinase 9 (MMP-9) activation, worse neurological outcomes, and poor survival rate at 10 days after CA/CPR. Administration of Na2S prevented the development of abnormal water diffusion and MMP-9 activation and markedly improved neurological function and long-term survival (9/12, P<0.05 vs. vehicle) after CA/CPR. These results suggest that administration of Na2S 1 min before CPR improves neurological function and survival rate at 10 days after CA/CPR by preventing water diffusion abnormality in the brain potentially via inhibiting MMP-9 activation early after resuscitation.
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影响因子：
4.2
作者：
Tyagi, Neetu;Givvimani, Srikanth;Qipshidze, Natia;Kundu, Soumi;Kapoor, Shray;Vacek, Jonathan C.;Tyagi, Suresh C.
通讯作者：
Tyagi, Suresh C.
影响因子：
4.2
作者：
Sen, Utpal;Munjal, Charu;Tyagi, Suresh C.
通讯作者：
Tyagi, Suresh C.
DOI：
10.1073/pnas.0705891104
发表时间：
2007-09-25
影响因子：
11.1
作者：
Elrod, John W.;Calvert, John W.;Lefer, David J.
通讯作者：
Lefer, David J.
影响因子：
6.3
作者：
Tejima, Emiri;Zhao, Bing-Qiao;Lo, Eng H.
通讯作者：
Lo, Eng H.
影响因子：
11.2
作者：
Wijman, Christine A. C.;Mlynash, Michael;Caulfield, Anna Finley;Hsia, Amie W.;Eyngorn, Irina;Bammer, Roland;Fischbein, Nancy;Albers, Gregory W.;Moseley, Michael
通讯作者：
Moseley, Michael