Rapid Neuronal Ultrastructure Disruption and Recovery during Spreading Depolarization-Induced Cytotoxic Edema
Rapid Neuronal Ultrastructure Disruption and Recovery during Spreading Depolarization-Induced Cytotoxic Edema
复制标题
扩散性去极化细胞毒性水肿过程中神经元超微结构的快速破坏与恢复
DOI：
10.1093/cercor/bhaa134
复制
发表时间：
2020-10-01
期刊：
影响因子：
3.7
通讯作者：
Sword, Jeremy
中科院分区：
文献类型：
--
作者：
Kirov, Sergei A.;Fomitcheva, Ioulia, V;Sword, Jeremy
在中风、头部外伤和心脏骤停等神经系统紧急情况期间导致急性脑损伤的两个主要致病事件是传播去极化波和相关的脑水肿，这些脑水肿穿过皮质损伤脑细胞。事实上，我们对去极化（SD）诱导的细胞毒性水肿在损伤后和恢复过程中如何在超微结构水平上演变一无所知。采用体内 2 光子成像和定量连续切片电子显微镜来评估氨基甲酸乙酯麻醉的雄性和雌性小鼠在短暂双侧颈总动脉闭塞引起的 SD 期间和之后新皮质中突触回路的完整性。 SD 引发树突状线粒体的快速断裂。肿胀的树突轴上突触密度的大幅增加意味着一些树突棘因肿胀而被淹没或仅仅缩回。总体突触密度没有变化。突触后树突膜仍然附着在轴突上，为突触回路的恢复提供了结构基础。立即再灌注后，细胞毒性水肿主要消退，树突超微结构的恢复证实了这一点。树突从肿胀和线粒体碎片的可逆性中恢复表明，改善组织灌注的神经重症监护应与针对线粒体恢复和最大限度减少 SD 发生的治疗同时进行。
Two major pathogenic events that cause acute brain damage during neurologic emergencies of stroke, head trauma, and cardiac arrest are spreading depolarizing waves and the associated brain edema that course across the cortex injuring brain cells. Virtually nothing is known about how spreading depolarization (SD)-induced cytotoxic edema evolves at the ultrastructural level immediately after insult and during recovery. In vivo 2-photon imaging followed by quantitative serial section electron microscopy was used to assess synaptic circuit integrity in the neocortex of urethane-anesthetized male and female mice during and after SD evoked by transient bilateral common carotid artery occlusion. SD triggered a rapid fragmentation of dendritic mitochondria. A large increase in the density of synapses on swollen dendritic shafts implies that some dendritic spines were overwhelmed by swelling or merely retracted. The overall synaptic density was unchanged. The postsynaptic dendritic membranes remained attached to axonal boutons, providing a structural basis for the recovery of synaptic circuits. Upon immediate reperfusion, cytotoxic edema mainly subsides as affirmed by a recovery of dendritic ultrastructure. Dendritic recuperation from swelling and reversibility of mitochondrial fragmentation suggests that neurointensive care to improve tissue perfusion should be paralleled by treatments targeting mitochondrial recovery and minimizing the occurrence of SDs.