Focal axon swelling refers to localized swelling in axons that may occur because of trauma (e.g., traumatic brain injury) or neurodegenerative diseases (e.g., Alzheimer’s disease). Since the swelling region can be many times larger than its original axon size, many researchers hypothesize that the swelling can alter the action potential (AP) signal. This article discusses the results of a series of newly developed computational studies to elucidate the possible intervention or blockage of AP signals due to swelling in the brain. We argue that the spherical geometry of the swelling site with its enlarged conducting interior causes the entering electric currents to spread evenly over the entire swelled membrane. As such, when the swelled surface becomes larger than the threshold size, the electric current will spread too thin to trigger the AP to spike. In this study, we have used a hybrid membrane model to simulate AP propagation across axons of different radii and swelling radii. We used an integrated model where a cylindrical symmetric 2D model is used to examine the electric current inside a spherical swelling site. In addition, two 1D models are used to capture the current flows along the upstream and downstream stretch before and after the swelling site. The parameters for this model are obtained from literature dedicated to modeling the experimental outcomes of mammal neurons. We observed two factors, which simultaneously affect AP transmission across a swelled axon: a) the axon radius and b) the ratio of the swelled and unswelled axon radii. In general, a thicker axon needs a smaller swelling size and axon ratio to block AP transmission. On the other hand, a thinner axon will reach the threshold at a larger swelling size and axon ratio. When only swelling size is considered, then thinner axons will block AP transmission at a smaller swelling radius. The AP transmission delay inside the swelled region determines whether the AP transmits forward or not. Notably, the blockage is worse if the AP fires at a high frequency. An increase in the charging and reset time due to swelling appears to be the main reason for the variation in axonal response.

中文翻译：

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局灶性轴突肿胀水平对动作电位信号传输的影响。

局灶性轴突肿胀是指由于外伤（如创伤性脑损伤）或神经退行性疾病（如， 阿尔茨海默氏病）。由于肿胀区域可能比其原始轴突大小大许多倍，因此许多研究人员假设肿胀可以改变动作电位 (AP) 信号。本文讨论了一系列新开发的计算研究的结果，以阐明由于大脑肿胀可能对 AP 信号进行干预或阻塞。我们认为膨胀部位的球形几何形状及其扩大的导电内部导致进入的电流均匀地分布在整个膨胀的膜上。因此，当膨胀表面变得大于阈值大小时，电流将传播得太细而无法触发 AP 尖峰。在这项研究中，我们使用混合膜模型来模拟 AP 跨不同半径和膨胀半径的轴突的传播。我们使用了一个集成模型，其中使用圆柱形对称 2D 模型来检查球形膨胀部位内的电流。此外，两个一维模型用于捕捉膨胀部位前后沿上游和下游延伸的电流。该模型的参数是从致力于模拟哺乳动物神经元实验结果的文献中获得的。我们观察到两个因素，它们同时影响膨胀轴突的 AP 传输：a) 轴突半径和 b) 膨胀和未膨胀轴突半径的比率。一般来说，较厚的轴突需要较小的膨胀尺寸和轴突比来阻止 AP 传输。另一方面，较薄的轴突将在较大的膨胀尺寸和轴突比率下达到阈值。当只考虑膨胀尺寸时，那么较薄的轴突将在较小的膨胀半径处阻止 AP 传输。膨胀区域内的AP传输延迟决定了AP是否向前传输。值得注意的是，如果 AP 以高频发射，则阻塞会更严重。由于肿胀导致充电和重置时间的增加似乎是轴突反应变化的主要原因。