Administration of Umbilical Cord Blood Cells Transiently Decreased Hypoxic-Ischemic Brain Injury in Neonatal Rats

被引:46
|
作者
Hattori, Tetsuo [1 ,2 ]
Sato, Yoshiaki [1 ]
Kondo, Taiki [1 ]
Ichinohashi, Yuko [1 ]
Sugiyama, Yuichiro [1 ]
Yamamoto, Michiro [3 ]
Kotani, Tomomi [4 ]
Hirata, Hitoshi [3 ]
Hirakawa, Akihiro [5 ]
Suzuki, Satoshi [5 ]
Tsuji, Masahiro [6 ]
Ikeda, Tomoaki [7 ]
Nakanishi, Keiko [8 ]
Kojima, Seiji [2 ]
Blomgren, Klas [9 ]
Hayakawa, Masahiro [1 ]
机构
[1] Nagoya Univ Hosp, Ctr Maternal Neonatal Care, Div Neonatol, Nagoya, Aichi 4668560, Japan
[2] Nagoya Univ, Grad Sch Med, Dept Pediat, Nagoya, Aichi 4648601, Japan
[3] Nagoya Univ, Grad Sch Med, Dept Hand Surg, Nagoya, Aichi 4648601, Japan
[4] Nagoya Univ, Grad Sch Med, Dept Obstet & Gynecol, Nagoya, Aichi 4648601, Japan
[5] Nagoya Univ, Grad Sch Med, Ctr Adv Med & Clin Res, Nagoya, Aichi 4648601, Japan
[6] Natl Cerebral & Cardiovasc Ctr, Res Inst, Dept Regenerat Med & Tissue Engn, Osaka, Japan
[7] Mie Univ, Dept Obstet & Gynecol, Tsu, Mie, Japan
[8] Aichi Human Serv Ctr, Inst Dev Res, Dept Perinatol, Kasugai, Aichi, Japan
[9] Karolinska Univ Hosp, Dept Womens & Childrens Hlth, Karolinska Inst, Stockholm, Sweden
关键词
Neuroprotection; Oxidative stress; Cell therapy; Asphyxia; NEURAL STEM-CELLS; SPINAL-CORD; BEHAVIORAL DEFICITS; MOUSE MODEL; DAMAGE; TRANSPLANTATION; HYPOTHERMIA; STROKE; ENCEPHALOPATHY; ANTIOXIDANTS;
D O I
10.1159/000368396
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
This study aimed to investigate whether the administration of mononuclear cells derived from human umbilical cord blood cells (UCBCs) could ameliorate hypoxic-ischemic brain injury in a neonatal rat model. The left carotid arteries of 7-day-old rats were ligated, and the rats were then exposed to 8% oxygen for 60 min. Mononuclear cells derived from UCBCs using the Ficoll-Hypaque technique were injected intraperitoneally 6 h after the insult (1.0 x 10(7) cells). Twentyfour hours after the insult, the number of cells positive for the oxidative stress markers 4-hydroxy-2-nonenal and nitrotyrosine, in the dentate gyrus of the hippocampus in the UCBC-treated group, decreased by 36 and 42%, respectively, compared with those in the control group. In addition, the number of cells positive for the apoptosis markers active caspase- 3 and apoptosis-inducing factor decreased by 53 and 58%, respectively. The number of activated microglia (ED1-positive cells) was 51% lower in the UCBC group compared with the control group. In a gait analysis performed 2 weeks after the insult, there were no significant differences among the sham-operated, control and UCBC groups. An active avoidance test using a shuttle box the following week also revealed no significant differences among the groups. Neither the volumes of the hippocampi, corpus callosum and cortices nor the numbers of neurons in the hippocampus were different between the UCBC and control groups. In summary, a single intraperitoneal injection of UCBC-derived mononuclear cells 6 h after an ischemic insult was associated with a transient reduction in numbers of apoptosis and oxidative stress marker-positive cells, but it did not induce long-term morphological or functional protection. Repeated administration or a combination treatment may be required to achieve sustained protection. (C) 2015 S. Karger AG, Basel
引用
收藏
页码:95 / 104
页数:10
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