Kemp Stephen W P, Walsh Sarah K, Zochodne Douglas W, Midha Rajiv
Department of Clinical Neuroscience, Faculty of Medicine, Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1.
J Neurosci Methods. 2007 Sep 15;165(1):83-8. doi: 10.1016/j.jneumeth.2007.05.032. Epub 2007 Jun 3.
Despite the capacity for spontaneous axonal regeneration, recovery following injuries to the peripheral nervous system (PNS) following transection are often incomplete and limited to short distances. Nerve growth factor (NGF) has been previously shown to support neuron survival, and direct growth of both developing and regenerating nerve fibers along a concentration gradient, based largely on in vitro studies. Here, we present a novel in vivo model of administering daily concentration gradients of NGF by directly manipulating the placement of the catheter-nerve conduit junction. Our results show that a dose of 800 pg NGF can be reliably used to establish a chemotactic concentration gradient over both a transient time period, and chronically through repeated daily administrations of the drug. Results from these studies may lead to a better mechanistic understanding of how concentration gradients of soluble NGF influence in vivo peripheral nerve regeneration.
尽管周围神经系统(PNS)具有轴突自发再生的能力,但横断损伤后的恢复往往不完全,且仅限于短距离。此前基于大量体外研究表明,神经生长因子(NGF)可支持神经元存活,并引导发育中和再生的神经纤维沿浓度梯度生长。在此,我们通过直接操纵导管-神经导管连接部位,提出了一种每日给予NGF浓度梯度的新型体内模型。我们的结果表明,800 pg的NGF剂量可可靠地用于在短暂时间段内以及通过每日重复给药长期建立趋化浓度梯度。这些研究结果可能有助于更好地从机制上理解可溶性NGF的浓度梯度如何影响体内周围神经再生。