What Was Observed? (Introduction)

• Peripheral nerves have a natural ability to heal themselves after injury, unlike the central nervous system (CNS).
• However, sometimes this repair process doesn’t work well, leading to permanent nerve damage and loss of sensation or movement.
• A drug called ivermectin, known for treating parasitic infections, was tested to see if it could help nerve regeneration in mammals, especially humans.
• In earlier experiments with frogs, ivermectin was shown to increase nerve growth in certain tissues, prompting scientists to test its effects in mammals.

What is Peripheral Nerve Regeneration?

• When peripheral nerves get damaged, specialized cells called Schwann cells help by clearing harmful substances and creating a healing environment for nerve growth.
• Sometimes, the Schwann cells don’t work properly, preventing full nerve repair, which is a major problem for humans who suffer nerve damage from trauma or diseases like diabetes.
• Scientists wanted to find a way to make nerve repair work better, and they looked at how other animals, like salamanders, heal nerves more efficiently.

What is Ivermectin and How Does It Work?

• Ivermectin is a drug used to treat infections caused by parasites, like scabies and worms.
• It works by affecting ion channels in cells, which can help trigger nerve growth and repair, even in mammals.
• The drug was already known to enhance nerve growth in frogs, so the research team tested it on mammalian cells to see if it could also help nerve repair in humans.

Study Design (Methods)

• Researchers tested ivermectin in both lab cultures (in vitro) and live animals (in vivo) to see how it affects nerve regeneration.
• In the lab, they grew human nerve stem cells (hiNSCs) alongside human skin cells (fibroblasts) in a special 3D environment.
• They treated the fibroblasts with ivermectin and studied how this affected the stem cells and their ability to grow and move.
• In live animals, they applied ivermectin to wounds and studied how it impacted wound healing and nerve growth.

What Did They Find? (Results)

• In the lab, ivermectin-treated fibroblasts caused the nerve stem cells to grow more rapidly and move faster toward injury sites, suggesting it helps nerves regenerate.
• These fibroblasts also started acting like glial cells, which are the cells that support and repair nerve tissue. They took up harmful substances and released growth factors that promote nerve healing.
• In live animals, wounds treated with ivermectin healed faster and showed more nerve growth, suggesting the drug can help repair peripheral nerves in mammals.
• After treatment, the skin cells showed characteristics similar to Schwann cells, which are crucial for nerve repair in the peripheral nervous system.

How Did Ivermectin Help? (Mechanism of Action)

• Ivermectin made fibroblasts act like glial cells by increasing their ability to take up harmful substances like glutamate, which can damage nerves if left untreated.
• The treated fibroblasts also started producing a protein called glial cell-derived neurotrophic factor (GDNF), which supports nerve growth and healing.
• Additionally, ivermectin caused the fibroblasts to change shape, becoming more like Schwann cells, which are critical for repairing peripheral nerves.

Wound Healing and Nerve Regeneration in Animals

• In live animal experiments, wounds treated with ivermectin showed faster healing and more nerve growth than untreated wounds.
• When the wound tissue was examined, researchers found higher levels of GDNF, glial fibrillary acidic protein (GFAP), and peripheral nerve markers, all of which are important for nerve regeneration.
• This suggests that ivermectin not only speeds up wound healing but also promotes the growth of new nerves in the injured area.

Conclusion (Discussion)

• These findings suggest that ivermectin could be a promising new treatment for enhancing nerve regeneration, especially in humans with nerve damage from conditions like diabetes or trauma.
• Ivermectin works by transforming fibroblasts into glial-like cells that support nerve repair, which is a novel approach for treating nerve injuries.
• Given that ivermectin is already FDA-approved and commonly used for treating parasitic infections, this opens the door for new clinical applications in nerve regeneration.
• While the results are promising, more research is needed to fully understand how ivermectin works in nerve repair and to explore its potential use in treating more severe nerve damage or conditions like neuropathy and spinal cord injuries.

观察到了什么？ (引言)

• 外周神经在损伤后有自我修复的能力，这与中枢神经系统（CNS）不同。
• 然而，有时这一修复过程不太有效，导致神经损伤和失去感觉或运动能力。
• 一种叫做伊维菌素的药物，已被用于治疗寄生虫感染，研究人员测试了它是否可以帮助哺乳动物的神经再生，特别是人类。
• 在以前的青蛙实验中，伊维菌素显示出能增加某些组织的神经生长，促使科学家在哺乳动物中测试它的效果。

什么是外周神经再生？

• 外周神经受损后，特化细胞——施旺细胞帮助清除有害物质，并为神经生长创造有利的修复环境。
• 有时，施旺细胞不能正常工作，无法完全修复神经，这对人类造成严重问题，尤其是从创伤或糖尿病等疾病中造成的神经损伤。
• 科学家们希望找到一种方法，使神经修复变得更有效，他们研究了其他动物（如蝾螈）是如何更高效地修复神经的。

伊维菌素是什么，它是如何工作的？

• 伊维菌素是一种用于治疗寄生虫感染的药物，如疥疮和蛔虫。
• 它通过影响细胞中的离子通道来发挥作用，这有助于触发神经生长和修复，即使在哺乳动物中。
• 该药物已被证明能够增强青蛙中的神经生长，因此研究团队在哺乳动物细胞上测试了它的效果，看看它是否能帮助神经修复。

研究设计（方法）

• 研究人员在实验室和活体动物中测试了伊维菌素，以观察它对神经再生的影响。
• 在实验室中，他们将人类神经干细胞（hiNSCs）与人类皮肤细胞（成纤维细胞）一起培养在特殊的3D环境中。
• 他们将这些成纤维细胞处理伊维菌素，研究它如何影响神经干细胞的生长和迁移。
• 在活体动物中，他们将伊维菌素应用于伤口，研究它对伤口愈合和神经生长的影响。

他们发现了什么？（结果）

• 在实验室中，伊维菌素处理的成纤维细胞使神经干细胞的生长速度更快，且向伤口部位的迁移速度更快，表明它有助于神经再生。
• 这些成纤维细胞还开始表现出类似神经胶质细胞的特征，能够清除有害物质并释放促进神经修复的生长因子。
• 在活体动物中，伊维菌素处理的伤口愈合速度更快，显示出更多的神经生长，表明这种药物有助于修复外周神经。
• 治疗后的皮肤细胞表现出类似施旺细胞的特征，这对修复外周神经至关重要。

伊维菌素如何帮助？（作用机制）

• 伊维菌素通过增加成纤维细胞吸收有害物质（如谷氨酸）的能力来发挥作用，这些物质如果不处理，可能会损害神经。
• 治疗后的成纤维细胞还开始产生一种叫做胶质细胞衍生神经营养因子（GDNF）的蛋白质，能够支持神经生长和愈合。
• 此外，伊维菌素使成纤维细胞发生形态变化，变得像施旺细胞一样，这对外周神经修复至关重要。

动物中伤口愈合和神经再生

• 在活体动物实验中，伊维菌素处理的伤口愈合速度更快，神经生长也更多。
• 当研究人员检查伤口组织时，发现治疗组中GDNF、胶质纤维酸性蛋白（GFAP）和外周神经标志物的表达水平显著提高，表明伊维菌素有助于神经生长。
• 这些发现表明，伊维菌素不仅加速了伤口愈合，还促进了伤口区域内神经的生长。

结论（讨论）

• 这些发现表明，伊维菌素可能成为一种有前途的治疗方法，可以增强神经再生，尤其适用于神经损伤的患者，如糖尿病或创伤后的患者。
• 伊维菌素通过将成纤维细胞转变为胶质样细胞，提供支持性环境，促进神经修复，这是一种创新的治疗方法。
• 鉴于伊维菌素已经获得FDA批准并广泛用于治疗寄生虫感染，这为其在神经再生中的临床应用提供了可能。
• 虽然这些结果很有希望，但仍需要更多的研究来全面了解伊维菌素在神经修复中的作用机制，并探索它在治疗更严重神经损伤或疾病（如神经病和脊髓损伤）中的潜力。