Sodium sulfide prevents water diffusion abnormality in the brain and improves long term outcome after cardiac arrest in mice

Kotaro Kida, Shizuka Minamishima, Huifang Wang, Jia Qian Ren, Kazim Yigitkanli, Ala Nozari, Joseph B. Mandeville, Philip K. Liu, Christina H. Liu, Fumito Ichinose

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


Aim of the study: 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. Methods: Adult male mice were subjected to potassium-induced CA for 7.5min at 37°C whereupon CPR was performed with chest compression and mechanical ventilation. Mice received Na2S (0.55mgkg-1 i.v.) or vehicle 1min before CPR. Results: 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. Conclusion: These results suggest that administration of Na2S 1min 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.

Original languageEnglish
Pages (from-to)1292-1297
Number of pages6
Issue number10
Publication statusPublished - 2012 Oct
Externally publishedYes


  • Blood brain barrier
  • Cardiac arrest
  • Hydrogen sulfide
  • Magnetic resonance imaging
  • Matrix metalloproteinase 9
  • Resuscitation

ASJC Scopus subject areas

  • Emergency Medicine
  • Emergency
  • Cardiology and Cardiovascular Medicine


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