Chu Kon, Park Kyung-Il, Lee Soon-Tae, Jung Keun-Hwa, Ko Song-Yi, Kang Lami, Sinn Dong-In, Lee Yong-Seok, Kim Seung U, Kim Manho, Roh Jae-Kyu
Stroke & Neural Stem Cell Laboratory in Clinical Research Institute, Department of Neurology, Seoul National University Hospital, 28, Yongon-dong, Chongro-gu, Seoul 110-744, South Korea.
Neurosci Res. 2005 Dec;53(4):384-90. doi: 10.1016/j.neures.2005.08.010. Epub 2005 Sep 28.
Recent studies have indicated the beneficial effects of vascular endothelial growth factor (VEGF), and transplanted neural stem cells (NSCs) in cerebral ischemia. We investigated the effects of the combined administration of NSCs and VEGF on focal cerebral ischemia in adult rats. Four groups (n = 12, respectively)--group 1 (ischemia-only), group 2 (ischemia + VEGF), group 3 (ischemia + NSCs) and group 4 (ischemia + NSCs + VEGF)--were compared. Human NSCs (HB1.F3), labeled with Lac Z+ or PKH26, were given intravenously 24h after surgery (5 x 10(6) cells). At 48 h after surgery, recombinant human VEGF (50 microg/kg) was infused intravenously (1 microg/(kg min)). Behavioral tests using the modified limb placing and rotarod tests were performed every week following ischemia. Immunohistochemistry for endothelial barrier antigen (EBA), VEGF and Nissl staining were performed at day 35 after ischemia. Group 4 showed better behavioral recovery at 7, 14 and 28 days than group 3 (p = 0.020, 0.005 and 0.043, respectively). These functional recoveries were correlated with enhanced EBA immunoreactivities at day 35 after ischemia, especially in the ipsilesional striatum. Group 4 showed lesser degree of brain atrophy in cortex and striatum, when compared with other groups. The distribution of VEGF was not co-localized with NSCs. Our results suggest that VEGF may act synergistically on NSC-transplanted, ischemic brain via a pro-angiogenic effect.
近期研究表明血管内皮生长因子（VEGF）以及移植的神经干细胞（NSCs）对脑缺血具有有益作用。我们研究了联合给予NSCs和VEGF对成年大鼠局灶性脑缺血的影响。比较了四组（每组n = 12）——第1组（仅缺血组）、第2组（缺血 + VEGF组）、第3组（缺血 + NSCs组）和第4组（缺血 + NSCs + VEGF组）。用Lac Z+或PKH26标记的人NSCs（HB1.F3）在手术后24小时静脉注射（5×10⁶个细胞）。手术后48小时，静脉注射重组人VEGF（50微克/千克）（1微克/（千克·分钟））。缺血后每周进行改良肢体放置和转棒试验等行为测试。缺血后第35天进行内皮屏障抗原（EBA）免疫组化、VEGF免疫组化和尼氏染色。第4组在第7、14和28天的行为恢复情况优于第3组（分别为p = 0.020、0.005和0.043）。这些功能恢复与缺血后第35天EBA免疫反应性增强相关，尤其是在同侧纹状体。与其他组相比，第4组皮质和纹状体的脑萎缩程度较小。VEGF的分布与NSCs不共定位。我们的结果表明，VEGF可能通过促血管生成作用对移植了NSCs的缺血脑发挥协同作用。
