Determining Neurotrophin Gradients in Vitro To Direct Axonal Outgrowth Following Spinal Cord Injury.,ACS Chemical Neuroscience

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Determining Neurotrophin Gradients in Vitro To Direct Axonal Outgrowth Following Spinal Cord Injury.
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2019-12-26 , DOI: 10.1021/acschemneuro.9b00565
Anusha Dravid ₁ , Sam Parittotokkaporn ₂ , Zaid Aqrawe _{1,

2} , Simon J O'Carroll ₂ , Darren Svirskis ₁

Affiliation

A spinal cord injury can damage neuronal connections required for both motor and sensory function. Barriers to regeneration within the central nervous system, including an absence of neurotrophic stimulation, impair the ability of injured neurons to reestablish their original circuitry. Exogenous neurotrophin administration has been shown to promote axonal regeneration and outgrowth following injury. The neurotrophins possess chemotrophic properties that guide axons toward the region of highest concentration. These growth factors have demonstrated potential to be used as a therapeutic intervention for orienting axonal growth beyond the injury lesion, toward denervated targets. However, the success of this approach is dependent on the appropriate spatiotemporal distribution of these molecules to ensure detection and navigation by the axonal growth cone. A number of in vitro gradient-based assays have been employed to investigate axonal response to neurotrophic gradients. Such platforms have helped elucidate the potential of applying a concentration gradient of neurotrophins to promote directed axonal regeneration toward a functionally significant target. Here, we review these techniques and the principles of gradient detection in axonal guidance, with particular focus on the use of neurotrophins to orient the trajectory of regenerating axons.

中文翻译：

在脊髓损伤后体外测定神经营养蛋白梯度以指导轴突生长。

脊髓损伤会损害运动和感觉功能所需的神经元连接。中枢神经系统内的再生障碍（包括缺乏神经营养刺激）削弱了受损神经元重建其原始回路的能力。已显示外源性神经营养蛋白给药可促进损伤后的轴突再生和生长。神经营养蛋白具有将轴突导向最高浓度区域的化学营养特性。这些生长因子已显示出潜力，可用于将轴突生长从损伤灶向神经支配的靶标定向。然而，该方法的成功取决于这些分子的适当时空分布，以确保通过轴突生长锥进行检测和导航。许多基于体外梯度的分析已被用于研究轴突对神经营养梯度的反应。这样的平台已经帮助阐明了应用神经营养蛋白浓度梯度来促进定向轴突再生向功能上重要的靶标的潜力。在这里，我们审查这些技术和轴突指导中的梯度检测的原理，特别着重于使用神经营养蛋白来定向再生轴突的轨迹。这样的平台已经帮助阐明了应用神经营养蛋白浓度梯度来促进定向轴突再生向功能上重要的靶标的潜力。在这里，我们审查这些技术和轴突指导中的梯度检测的原理，特别着重于使用神经营养蛋白来定向再生轴突的轨迹。这样的平台已经帮助阐明了应用神经营养蛋白浓度梯度来促进定向轴突再生向功能上重要的靶标的潜力。在这里，我们审查这些技术和轴突指导中的梯度检测的原理，特别着重于使用神经营养蛋白来定向再生轴突的轨迹。

更新日期：2019-12-27

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