Zhao Fengyu, Kuroiwa Toshihiko, Miyasaka Naoyuki, Nagaoka Tsukasa, Nakane Makoto, Tamura Akira, Mizusawa Hidehiro
Department of Neurology and Neurological Science, Medical Research Institute, Tokyo Medical and Dental University, Japan.
Neuropathology. 2002 Sep;22(3):91-105. doi: 10.1046/j.1440-1789.2002.00437.x.
To clarify the morphological characteristics of exofocal post-ischemic neuronal death (EPND) in the substantia nigra (SN), we investigated the course of light- and electron-microscopic changes of the SN of rats subjected to occlusion of the left middle cerebral artery (MCA) for 1, 2, 4, 7 and 12 days. To assess cellular edema, sequential magnetic resonance (MR) mapping of the apparent diffusion coefficient (ADC) and the T2 value test was performed. Histological and electron-microscopic examination on day 1 showed dotted chromatin clumps in the nuclei of some neurons and mild swelling of the perivascular endfeet of astrocytes in the ipsilateral SN. On day 2, a few cells of the ipsilateral SN pars reticulata (SNr) revealed key morphological signs of apoptosis--apoptotic body-like condensation and segregation of the chromatin and DNA fragmentation-like nuclear remnants. On day 4, 38% of neurons became swollen (pale neurons) with cytoplasmic microvacuoles, which appeared to originate from rough endoplasmic reticulum (rER), mitochondria and Golgi apparatus. Twenty percent of neurons showed massive proliferation of the cisternae of the rER, some of which were fragmented or had lost their normal parallel arrangement. In addition, MR mapping revealed a transient ADC decrease with a T2 increase (signifying a phase of cellular edema), which coordinated with the phase of ultrastructural cellular swelling. Further, the total number of neurons started to decrease gradually, the perivascular endfeet of astrocytes were markedly swollen, and the neuropil became loose on day 4. On day 7, reactive astrocytes and dark neurons occurred most frequently. These results suggest that the EPND in the SN after occlusion of the MCA in adult rats is due to both apoptosis and necrosis, although necrosis seems to be the dominant mechanism of the EPND. However, the morphologic resemblances of EPND to delayed neuronal death suggest these processes have a common pathomechanism.
为阐明黑质（SN）中外侧缺血后神经元死亡（EPND）的形态学特征，我们研究了左大脑中动脉（MCA）闭塞1、2、4、7和12天的大鼠SN的光镜和电镜变化过程。为评估细胞水肿，进行了表观扩散系数（ADC）和T2值测试的序列磁共振（MR）成像。第1天的组织学和电镜检查显示，同侧SN中一些神经元的细胞核内有散在的染色质团块，星形胶质细胞的血管周围终足轻度肿胀。第2天，同侧SN网状部（SNr）的一些细胞出现了凋亡的关键形态学特征——染色质和DNA片段化样核残余物的凋亡小体样凝聚和分离。第4天，38%的神经元肿胀（苍白神经元），伴有细胞质微泡，这些微泡似乎起源于粗面内质网（rER）、线粒体和高尔基体。20%的神经元显示rER池大量增生，其中一些断裂或失去了正常的平行排列。此外，MR成像显示ADC短暂降低，T2升高（表明细胞水肿阶段），这与超微结构细胞肿胀阶段一致。此外，第4天神经元总数开始逐渐减少，星形胶质细胞的血管周围终足明显肿胀，神经毡变得疏松。第7天，反应性星形胶质细胞和深色神经元最为常见。这些结果表明，成年大鼠MCA闭塞后SN中的EPND是由凋亡和坏死共同引起的，尽管坏死似乎是EPND的主要机制。然而，EPND与迟发性神经元死亡的形态学相似性表明这些过程具有共同的发病机制。
