Effect of repeated allogeneic bone marrow mononuclear cell transplantation on brain injury following transient focal cerebral ischemia in rats

详细信息    查看全文

• 作者：Fumio Kamiya ; Masayuki Ueda ; Chikako Nito ; Nobuo Kamiya ; Toshiki Inaba ; Satoshi Suda ; Tomonari Saito ; Kanako Muraga ; Yasuo Katayama
• 关键词：Bone marrow ; Cerebral ischemia ; Neuroprotection ; Allogeneic transplantation
• 刊名：Life Sciences
• 出版年：24 January, 2014
• 年：2014
• 卷：95
• 期：1
• 页码：22-28
• 全文大小：478 K

文摘

Aims

Transplantation of bone marrow mononuclear cells (BMMCs) exerts neuroprotection against cerebral ischemia. We examined the therapeutic timepoint of allogeneic BMMC transplantation in a rat model of focal cerebral ischemia, and determined the effects of repeated transplantation outside the therapeutic window.

Main methods

Male Sprague-Dawley rats were subjected to 90 minute focal cerebral ischemia, followed by intravenous administration of 1 脳 10⁷ allogeneic BMMCs or vehicle at 0, 3 or 6 h after reperfusion or 2 脳 10⁷ BMMCs 6 h after reperfusion. Other rats administered 1 脳 10⁷ BMMCs at 6 h after reperfusion received additional BMMC transplantation or vehicle 9 h after reperfusion. Infarct volumes, neurological deficit scores and immunohistochemistry were evaluated 24 or 72 h after reperfusion.

Key findings

Infarct volumes at 24 h were significantly decreased in transplantation rats at 0 and 3 h, but not at 6 h, after reperfusion, compared to vehicle-treatment. Even high dose BMMC transplantation at 6 h after reperfusion was ineffective. Repeated BMMC transplantation at 6 and 9 h after reperfusion reduced infarct volumes and significantly improved neurological deficit scores at 24 and 72 h. Immunohistochemistry showed repeated BMMC transplantation reduced ionized calcium-binding adapter molecule 1, 4-hydroxy-2-nonenal and 8-hydroxydeoxyguanosine expression at 24 and 72 h after reperfusion.

Significance

Intravenous allogeneic BMMCs were neuroprotective following transient focal cerebral ischemia, and the therapeutic time window of BMMC transplantation was > 3 h and < 6 h after reperfusion in this model. Repeated transplantation at 6 and 9 h after reperfusion suppressed inflammation and oxidative stress in ischemic brains, resulting in improved neuroprotection.