Han Chang-Woo, Lee Kyung-Hwa, Noh Myung Giun, Kim Jin-Myung, Kim Hyung-Seok, Kim Hyung-Sun, Kim Ra Gyung, Cho Jongwook, Kim Hyoung-Ihl, Lee Min-Cheol
Department of Pathology, Chonnam National University Medical School and Research Institute of Medical Sciences, Gwangju, Korea.
Department of Forensic Medicine, Chonnam National University Medical School and Research Institute of Medical Sciences, Gwangju, Korea.
J Pathol Transl Med. 2017 May;51(3):292-305. doi: 10.4132/jptm.2017.02.17. Epub 2017 May 10.
Stroke involving the cerebral white matter (WM) has increased in prevalence, but most experimental studies have focused on ischemic injury of the gray matter. This study was performed to investigate the WM in a unique rat model of photothrombotic infarct targeting the posterior limb of internal capsule (PLIC), focusing on the identification of the most vulnerable structure in WM by ischemic injury, subsequent glial reaction to the injury, and the fundamental histopathologic feature causing different neurologic outcomes.
Light microscopy with immunohistochemical stains and electron microscopic examinations of the lesion were performed between 3 hours and 21 days post-ischemic injury.
Initial pathological change develops in myelinated axon, concomitantly with reactive change of astrocytes. The first pathology to present is nodular loosening to separate the myelin sheath with axonal wrinkling. Subsequent pathologies include rupture of the myelin sheath with extrusion of axonal organelles, progressive necrosis, oligodendrocyte degeneration and death, and reactive gliosis. Increase of glial fibrillary acidic protein (GFAP) immunoreactivity is an early event in the ischemic lesion. WM pathologies result in motor dysfunction. Motor function recovery after the infarct was correlated to the extent of PLIC injury proper rather than the infarct volume.
Pathologic changes indicate that the cerebral WM, independent of cortical neurons, is highly vulnerable to the effects of focal ischemia, among which myelin sheath is first damaged. Early increase of GFAP immunoreactivity indicates that astrocyte response initially begins with myelinated axonal injury, and supports the biologic role related to WM injury or plasticity. The reaction of astrocytes in the experimental model might be important for the study of pathogenesis and treatment of the WM stroke.
涉及脑白质（WM）的中风患病率有所上升，但大多数实验研究都集中在灰质的缺血性损伤上。本研究旨在通过一种独特的光血栓性梗死大鼠模型来研究内囊后肢（PLIC）的白质，重点是通过缺血性损伤确定白质中最易受损的结构、随后神经胶质细胞对损伤的反应以及导致不同神经学结果的基本组织病理学特征。
在缺血性损伤后3小时至21天之间，对病变进行免疫组织化学染色的光学显微镜检查和电子显微镜检查。
最初的病理变化发生在有髓轴突，同时伴有星形胶质细胞的反应性变化。首先出现的病理变化是结节状疏松，使髓鞘与轴突皱缩分离。随后的病理变化包括髓鞘破裂伴轴突细胞器挤出、进行性坏死、少突胶质细胞变性和死亡以及反应性胶质增生。胶质纤维酸性蛋白（GFAP）免疫反应性增加是缺血性病变中的早期事件。白质病变导致运动功能障碍。梗死灶后的运动功能恢复与PLIC本身的损伤程度相关，而不是与梗死体积相关。
病理变化表明，脑白质独立于皮质神经元，极易受到局灶性缺血的影响，其中髓鞘首先受损。GFAP免疫反应性的早期增加表明星形胶质细胞反应最初始于有髓轴突损伤，并支持与白质损伤或可塑性相关的生物学作用。实验模型中星形胶质细胞的反应可能对研究白质中风的发病机制和治疗具有重要意义。
