Effect of VEGF on Inflammatory Regulation, Neural Survival, and Functional Improvement in Rats following a Complete Spinal Cord Transection.
Effect of VEGF on Inflammatory Regulation, Neural Survival, and Functional Improvement in Rats following a Complete Spinal Cord Transection.
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DOI：
10.3389/fncel.2017.00381
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发表时间：
2017
影响因子：
5.3
通讯作者：
Wu W
中科院分区：
文献类型：
--
作者：
Li J;Chen S;Zhao Z;Luo Y;Hou Y;Li H;He L;Zhou L;Wu W
在完全横断胸段脊髓后，新生大鼠表现出后肢的自发运动恢复，但这种恢复在成年大鼠类似的损伤后没有发现。与新生大鼠和成年大鼠恢复差异相关的潜在机制尚不清楚。在这项研究中，分析了342只动物。与28日龄成年大鼠（P28）相比，出生后1天大鼠（P1）在完全T9横断后，损伤部位以下脊髓节段中的血管内皮生长因子（VEGF）水平显著较高。VEGF管理P28大鼠T9横断显著改善功能恢复;相反，VEGF受体抑制剂治疗P1大鼠T9横断减慢自发功能恢复。结果显示，P28组大鼠损伤后脊髓神经元数目减少，损伤部位下局部神经网络重组情况较P1组差。伪狂犬病病毒跨突触追踪和免疫荧光双标分析表明，VEGF治疗P28大鼠减轻了神经元数量的减少，并改善了其网络重组。新生儿VEGF抑制导致高神经元死亡率和网络重组恶化。在体内研究中，T9横切诱导P1动物脊髓中小胶质细胞数量的增加少于P28动物。VEGF治疗减少了P28动物中小胶质细胞的增加。在培养的脊髓运动神经元VEGF管理防止脂多糖（LPS）诱导的神经元死亡，促进轴突生长。Western blot结果显示，脊髓损伤或LPS诱导后，脊髓运动神经元Erk 1/2磷酸化水平均低于对照组。VEGF处理后磷酸化水平升高。总之，VEGF是参与脊髓横断后功能恢复的关键介质，可以被认为是临床治疗的潜在靶点。
After complete transection of the thoracic spinal segment, neonatal rats exhibit spontaneous locomotor recovery of hindlimbs, but this recovery is not found in adult rats after similar injury. The potential mechanism related to the difference in recovery of neonatal and adult rats remains unknown. In this study, 342 animals were analyzed. The vascular endothelial growth factor (VEGF) level in spinal segments below injury sites was significantly higher in postnatal day 1 rats (P1) compared with 28-day-old adult rats (P28) following a complete T9 transection. VEGF administration in P28 rats with T9 transection significantly improved the functional recovery; by contrast, treatment with VEGF receptor inhibitors in P1 rats with T9 transection slowed down the spontaneous functional recovery. Results showed more neurons reduced in the lumbar spinal cord and worse local neural network reorganization below injury sites in P28 rats than those in P1 rats. Transynaptic tracing with pseudorabies virus and double immunofluorescence analysis indicated that VEGF treatment in P28 rats alleviated the reduced number of neurons and improved their network reorganization. VEGF inhibition in neonates resulted in high neuronal death rate and deteriorated network reorganization. In in vivo studies, T9 transection induced less increase in the number of microglia in the spinal cord in P1 animals than P28 animals. VEGF treatment reduced the increase in microglial cells in P28 animals. VEGF administration in cultured spinal motoneurons prevented lipopolysaccharide (LPS)-induced neuronal death and facilitated neurite growth. Western blots of the samples of lumbar spinal cord after spinal transection and cultured spinal motoneurons showed a lower level of Erk1/2 phosphorylation after the injury or LPS induction compared with that in the control. The phosphorylation level increased after VEGF treatment. In conclusion, VEGF is a critical mediator involved in functional recovery after spinal transection and can be considered a potential target for clinical therapy.
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影响因子：
6.1
作者：
Hu J;Selzer ME
通讯作者：
Selzer ME
影响因子：
6
作者：
Beazley-Long, Nicholas;Hua, Jing;Donaldson, Lucy F.
通讯作者：
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影响因子：
3.3
作者：
Bhuiyan, M. I. H.;Kim, J. -C.;Kim, S. Y.
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Kim, S. Y.
影响因子：
2.5
作者：
BERNSTEIN, DR;BECHARD, DE;STELZNER, DJ
通讯作者：
STELZNER, DJ
影响因子：
7.7
作者：
Hwang WW;Salinas RD;Siu JJ;Kelley KW;Delgado RN;Paredes MF;Alvarez-Buylla A;Oldham MC;Lim DA
通讯作者：
Lim DA