Hiraizumi Y, Fujimaki E, Transfeldt E E, Kawahara N, Fiegel V D, Knighton D, Sung J H
Department of Orthopaedic Surgery, Showa University, Tokyo, Japan.
Spinal Cord. 1996 Jul;34(7):394-402. doi: 10.1038/sc.1996.71.
The main purpose of this study is to investigate the effect of platelet derived wound healing formula (PDWHF) and nerve growth factor (NGF) in the treatment of experimental spinal cord injury. PDWHF is a conglomerate of growth factors which include platelet derived growth factor (PDGF), platelet derived angiogenesis factor (PDAF), transforming growth factor-beta (TGF beta) and platelet factor IV (PF4). Complete spinal cord transection was performed at T12 in rats and the treatment of the spinal cord injury was achieved by filling the dead space with type 1 collagen gel impregnated with PDWHF, or with 2.5S-NGF. Controls were treated with only type 1 collagen gel. Animals were sacrificed at 1, 2 or 3 months. Histopathologically, tissue autolysis and cavity formation by phagocytosis expanded 1-3 mm into the cord stumps and the volume of cavitation was less in the two treated groups. In the NGF group, a greater number of surviving nerve cells were observed in this region. Most of the control animals formed only thin, short axonal bundles, however, increased axonal regrowth was noted in animals treated with trophic factors, especially in the NGF group. The NGF group formed thick axonal bundles and abundant neuroma. Increased angiogenesis was observed in the collagen gel matrix and the injured spinal cord parenchyma, in the PDWHF group. Recent studies have shown that mammalian adult CNS possesses the ability for structural and/or functional plasticity following injury under appropriate circumstances. In this in vivo study, exogenous NGF appeared to induce axomal outgrowth and nerve cell survival. PDWHF produced notable angiogenesis which seemed to improve the extracellular microenvironment. This may be important for the delivery of exogenous trophic factors, nutrients and for the changes of extracellular matrices to support nerve cells and axons.
本研究的主要目的是探讨血小板源性伤口愈合配方(PDWHF)和神经生长因子(NGF)在治疗实验性脊髓损伤中的作用。PDWHF是一种生长因子的聚合体,其中包括血小板源性生长因子(PDGF)、血小板源性血管生成因子(PDAF)、转化生长因子-β(TGF-β)和血小板因子IV(PF4)。在大鼠的T12水平进行完全性脊髓横断,并通过用浸渍有PDWHF的I型胶原凝胶或2.5S-NGF填充死腔来治疗脊髓损伤。对照组仅用I型胶原凝胶治疗。在1、2或3个月时处死动物。组织病理学检查显示,组织自溶和吞噬作用形成的空洞向脊髓残端扩展1-3毫米,两个治疗组的空洞体积较小。在NGF组中,在该区域观察到更多存活的神经细胞。大多数对照动物仅形成细而短的轴突束,然而,在用营养因子治疗的动物中,尤其是在NGF组中,轴突再生增加。NGF组形成了粗大的轴突束和丰富的神经瘤。在PDWHF组中,在胶原凝胶基质和损伤的脊髓实质中观察到血管生成增加。最近的研究表明,哺乳动物成年中枢神经系统在适当情况下损伤后具有结构和/或功能可塑性的能力。在这项体内研究中,外源性NGF似乎诱导了轴突生长和神经细胞存活。PDWHF产生了显著的血管生成,这似乎改善了细胞外微环境。这对于外源性营养因子、营养物质的传递以及细胞外基质的变化以支持神经细胞和轴突可能很重要。