Trejos A Jesus, Schanne A X Francis
St. John's University Queens, Jamaica, NY, USA.
Regeneron Pharmaceuticals, Tarrytown, NY, USA.
Cell Mol Neurobiol. 2025 Apr 9;45(1):34. doi: 10.1007/s10571-025-01545-1.
The dendritic cell of the CNS, the microglia (MG), is an initiation point of the immunological response within the post-blood-brain barrier (BBB) compartment. Microglia drastically changes in response to cell stress to a much different non-dendritic morphologies. This investigation postulates that if the first MG responses to toxic injury are isolated and studied in greater morphological detail, there is much to be learned about microglia's metamorphosis from and M2 to an M1 state. The organotypic hippocampal slice was the experimental setting used to investigate microglial response to toxic injury; this isolates dendritic cell to post-BBB cells dynamics from the impact of nonspecific of in vivo blood-derived signaling. Within the context of biochemically verified precise toxic cell injury/death (induced with mercury or cyanide in combination with 2-deoxy-glucose) to a specific region within the hippocampal slice, MG's morphological response was evaluated. There was up to 35% increase in microglia activation proximally to injury (CA3 region) and no changes distally (DG region) when compared to control slices treated with PBS. Maximum microglia activation consisted of a 3 plus-fold increase in the distance between the nucleus membrane and the cell membrane, which underscores an extensive and quantifiable amount of membrane rearrangement. This quantification can be applied to contemporaneous AI image analysis algorithms to demarcate and quantify relative MG activation in and around a site of injury. In between baseline and activated MG morphologies, 5 intermediate morphologies (or structural variations) are described as it relates to its cell body, nucleus, and dendrites. The result from this study reconciles details of MG's structure to its holistic characteristics in relation to parenchymal cell stress.
中枢神经系统的树突状细胞——小胶质细胞（MG），是血脑屏障（BBB）后区室免疫反应的起始点。小胶质细胞会因细胞应激而急剧变化，呈现出与非树突状形态截然不同的形态。本研究假定，如果能分离并更详细地从形态学角度研究小胶质细胞对毒性损伤的最初反应，那么就能更多地了解小胶质细胞从M2状态转变为M1状态的过程。器官型海马切片是用于研究小胶质细胞对毒性损伤反应的实验设置；这将树突状细胞到血脑屏障后细胞的动态变化与体内血液来源信号的非特异性影响隔离开来。在通过生物化学方法验证了对海马切片特定区域的精确毒性细胞损伤/死亡（用汞或氰化物与2-脱氧葡萄糖联合诱导）的背景下，评估了小胶质细胞的形态学反应。与用磷酸盐缓冲盐水处理的对照切片相比，损伤近端（CA3区）的小胶质细胞激活增加了35%，而远端（DG区）则没有变化。小胶质细胞的最大激活表现为核膜与细胞膜之间的距离增加了3倍多，这突出了大量且可量化的膜重排。这种量化可应用于同期的人工智能图像分析算法，以划分和量化损伤部位及其周围的相对小胶质细胞激活情况。在基线和激活的小胶质细胞形态之间，描述了5种中间形态（或结构变化），涉及细胞体、细胞核和树突。本研究结果将小胶质细胞的结构细节与其在实质细胞应激方面的整体特征进行了整合。
