Pulsed magnetic fields, neurons, and blood vessels

描述（由申请人提供）：脉冲磁场（PMF）产生的信号已被添加到愈合骨折的标准策略列表中，最近的证据表明，软组织伤口愈合的其他临床应用。几种相互关联的机制可能解释了PMF修复组织的能力，包括血管生成、细胞内钙的调节和生长因子合成的刺激。值得注意的是，这些相同的机制在脑细胞的维持和可塑性方面发挥着重要和关键的作用。我们研究的长期目标是增加帕金森病中多巴胺能神经元的存活率，在过去的几年里，我们一直专注于多巴胺能神经元，血管生成因子和脑血管形成之间的关系。最近，我们观察到多巴胺能神经元与神经移植中的血管有很强的联系，并发现血管内皮生长因子（VEGF），一种血管生成因子，可以伴随增加神经元的存活。来自我们实验室的初步数据表明，血管可塑性的分子和细胞指标随着年龄的增长而下降，这表明血管的维持和功能可能会受到损害，对神经元的存活产生负面影响。我们假设，PMF将增加血管可塑性和神经元的存活在大鼠，这种效果可能是最大的老年动物。我们建议研究PMF对细胞培养、完整脑和神经移植中的神经元和血管的影响。我们将使用PMF的各种条件来优化效果（或确认不存在效果）。与目前正在研究PMF和伤口愈合的Montefiore显微外科实验室以及研究PMF生物学效应超过30年的生物药理学家合作，我们将探索这种方式减轻神经变性和增加血管可塑性的潜力。结果不仅可以应用于帕金森病的治疗策略，而且可以用于治疗其他慢性和急性血管和神经退行性疾病。

DESCRIPTION (provided by applicant): Signals generated by pulsed magnetic fields (PMF) have been added to the list of standard strategies in healing bone fractures, and recent evidence suggests additional clinical applications for wound healing in soft tissue. Several interrelated mechanisms may account for the ability of PMF to repair tissue, including angiogenesis, regulation of intracellular calcium, and stimulation of growth factor synthesis. Notably, these same mechanisms play important and critical roles in the maintenance and plasticity of brain cells. The longterm goal of our research is to increase the survival of dopaminergic neurons in Parkinson's disease, and for the past several years we have focused on the relationship between dopaminergic neurons, angiogenic factors, and brain vascularization. Recently we observed that dopaminergic neurons have a strong association with blood vessels in neural transplants, and found that VEGF (vascular endothelial growth factor), an angiogenic factor, could concomitantly increase neuronal survival. Preliminary data from our laboratory indicates that molecular and cellular indices of vascular plasticity decline with aging, suggesting that vessel maintenance and function may be compromised, negatively impacting on neuronal survival. We hypothesize that PMF will increase vascular plasticity and neuronal survival in rats, and this effect may be greatest for aged animals. We propose to examine the effects of PMF on neurons and vessels in cell culture, intact brain, and neural transplants. We will use a variety of conditions of PMF to optimize the effect (or to confirm the absence of an effect). In collaboration with the microsurgery laboratory at Montefiore currently studying PMF and wound healing, and a biophysicist who has studied the biological effects of PMF for more than 30 years, we will explore the potential of this modality to attenuate neurodegeneration and increase vascular plasticity. Results could have applications not only in therapeutic strategies for Parkinson's disease, but in the treatment of other chronic and acute vascular and neurodegenerative diseases.