神经科学家和细胞生物学家几十年来一直知道真核细胞，包括神经元，都被由磷脂双层组成的质膜/轴膜所包围，它可以调节离子（包括钙离子）和其他物质的跨膜扩散。细胞通常通过外伤和各种疾病导致质膜受损。如果受损的质膜不能在几分钟内快速修复，钙离子流入会激活凋亡途径，导致细胞死亡。我们回顾了报道得比较少的内容（尚未在神经科学或细胞生物学教科书中介绍）：伤口处从小型纳米孔到完全轴突断裂的钙离子流入激活了平行的生物化学途径，诱导囊泡/膜结构迁移和相互作用，以恢复原始的屏障特性，并最终重新建立质膜。我们评估了各种措施（如膜电压、输入电阻、电流流量、示踪染料、共聚焦显微镜、透射和扫描电子显微镜）的可靠性和问题，这些措施单独或组合在不同的细胞类型（如无脊椎动物巨大轴突、卵母细胞、海马和其他哺乳动物神经元）中用于评估质膜密封。我们确定争议，例如尝试解释目前可用的质膜修复/密封的亚细胞机制的塞子与补丁假说。我们描述目前的研究缺口和潜在未来发展，例如将生物化学/生物物理措施与亚细胞微观形态学进行更广泛的相关性。我们对比自然密封和最近发现的通过聚乙二醇（PEG）诱导的质膜密封。PEG可以绕过所有自然膜修复途径。我们评估其他最近的发展，例如邻近细胞在相邻细胞受伤后的自适应膜响应。最后，我们推测，更好地理解自然和人工质膜密封的机制对于开发更好的临床治疗肌肉萎缩症、中风和其他缺血性疾病以及各种癌症是必要的。版权所有©2023 Mencel 和 Bittner。

Neuroscientists and Cell Biologists have known for many decades that eukaryotic cells, including neurons, are surrounded by a plasmalemma/axolemma consisting of a phospholipid bilayer that regulates trans-membrane diffusion of ions (including calcium) and other substances. Cells often incur plasmalemmal damage via traumatic injury and various diseases. If the damaged plasmalemma is not rapidly repaired within minutes, activation of apoptotic pathways by calcium influx often results in cell death. We review publications reporting what is less-well known (and not yet covered in neuroscience or cell biology textbooks): that calcium influx at the lesion sites ranging from small nm-sized holes to complete axonal transection activates parallel biochemical pathways that induce vesicles/membrane-bound structures to migrate and interact to restore original barrier properties and eventual reestablishment of the plasmalemma. We assess the reliability of, and problems with, various measures (e.g., membrane voltage, input resistance, current flow, tracer dyes, confocal microscopy, transmission and scanning electron microscopy) used individually and in combination to assess plasmalemmal sealing in various cell types (e.g., invertebrate giant axons, oocytes, hippocampal and other mammalian neurons). We identify controversies such as plug versus patch hypotheses that attempt to account for currently available data on the subcellular mechanisms of plasmalemmal repair/sealing. We describe current research gaps and potential future developments, such as much more extensive correlations of biochemical/biophysical measures with sub-cellular micromorphology. We compare and contrast naturally occurring sealing with recently-discovered artificially-induced plasmalemmal sealing by polyethylene glycol (PEG) that bypasses all natural pathways for membrane repair. We assess other recent developments such as adaptive membrane responses in neighboring cells following injury to an adjacent cell. Finally, we speculate how a better understanding of the mechanisms involved in natural and artificial plasmalemmal sealing is needed to develop better clinical treatments for muscular dystrophies, stroke and other ischemic conditions, and various cancers.Copyright © 2023 Mencel and Bittner.