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Effect of Adipose-Derived Mesenchymal Stem Cell Administration and Mild Hypothermia Induction on Delayed Neuronal Death After Transient Global Cerebral Ischemia

Chung, Tae Nyoung MD, PhD1; Kim, Jin Hee PhD2; Choi, Bo Young PhD2; Jeong, Ju-Yeon BS3; Chung, Sung Phil MD, PhD4; Kwon, Sung Won MD, PhD5; Suh, Sang Won MD, PhD2

doi: 10.1097/CCM.0000000000002289
Online Laboratory Investigations

Objectives: Global cerebral ischemia is a cause of poor prognosis after resuscitation from cardiac arrest. Various attempts have been made to minimize global cerebral ischemia but none been more effective than mild hypothermia induction. A few studies have shown the effect of mesenchymal stem cells on global cerebral ischemia, but no studies have compared this effect with mild hypothermia or assessed any possible interaction. We aimed to show the effect of mesenchymal stem cells on delayed neuronal death after global cerebral ischemia and to compare this effect with mild hypothermia.

Design: Experimental study.

Setting: Animal research laboratory.

Subjects: Adult male Sprague-Dawley rats weighing 250–300 g.

Interventions: Rats were subjected to 7 minutes of transient global cerebral ischemia and randomized into four groups: control, mild hypothermia, injection of human adipose-derived mesenchymal stem cells, and combined application of mild hypothermia and mesenchymal stem cells, along with four sham groups treated identically. Rats were euthanized 7 days after global cerebral ischemia.

Measurements and Main Results: Degree of neuronal death in hippocampus was significantly higher in control than in other groups. The number of activated microglia was higher in control group than in other groups and was higher in mild hypothermia than shams, mesenchymal stem cells, mild hypothermia/mesenchymal stem cells. Degree of blood-brain barrier disruption and the count of infiltrated neutrophils were significantly higher in control than in other groups. Degree of oxidative injury was significantly higher in control than other groups. It was higher in mild hypothermia than sham groups, mesenchymal stem cells, mild hypothermia/mesenchymal stem cells and was higher in mesenchymal stem cells group than sham groups. Significantly, worse functional results were found in control than in other groups.

Conclusions: Administration of mesenchymal stem cells after transient global cerebral ischemia has a prominent protective effect on delayed neuron death, even compared with mild hypothermia.

1Department of Emergency Medicine, CHA University School of Medicine, Seongnam, Gyeonggi-Do, Korea.

2Department of Physiology, Hallym University College of Medicine, Chuncheon, Korea.

3Institute for Clinical Research, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Gyeonggi-Do, Korea.

4Department of Emergency Medicine, Yonsei University College of Medicine, Seoul, Korea.

5Department of Surgery, CHA University School of Medicine, Seongnam Gyeonggi-Do, Korea.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

Basic Science Research Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Science, ICT & Future Planning (NRF-2013R1A1A1005486) to Dr. Chung. Brain Research Program through the NRF of Korea funded by the Ministry of Science, ICT & Future Planning (NRF-2016M3C7A1913844) to Dr. Suh.

The authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: swsuh@hallym.ac.kr

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