Oligodendroglial cell death with DNA fragmentation in the white matter under chronic cerebral hypoperfusion: comparison between normotensive and spontaneously hypertensive rats
Oligodendroglial cell death with DNA fragmentation in the white matter under chronic cerebral hypoperfusion: comparison between normotensive and spontaneously hypertensive rats
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DOI：
10.1016/s0168-0102(01)00195-x
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发表时间：
2001-04-01
影响因子：
2.9
通讯作者：
Sawada, T
中科院分区：
文献类型：
--
作者：
Masumura, M;Hata, R;Sawada, T
本研究观察了正常血压Wistar京都大鼠（WKY）和自发性高血压大鼠（SHR）双侧颈动脉结扎（BCAL）后白色物质的神经病理学和生化变化。BCAL后1周，WKY和SHR均出现白色物质稀疏、空泡化，少突胶质细胞减少，但WKY和SHR之间无差异。另一方面，空泡形成的少突胶质细胞死亡显着增加，从2至4周的视束和穹窿海马伞的低灌注SHR。此外，末端脱氧核苷酸转移酶介导的dUTP原位缺口末端标记（TUNEL）阳性细胞和凝集素阳性小胶质细胞的数量和染色强度增加更显着的SHR比WKY。原位细胞死亡检测ELISA定量支持这些结果。RT-PCR检测了BCAL后WKY和SHR脑组织TNF-α、TNF受体1（p55）、caspase-2（Ich-1）和caspase-3（CF'P32）mRNA的表达。免疫组织化学分析显示，TNF-α，TNF受体1（p55），Ich-1和CPP 32免疫反应细胞也可以在低灌注SHR的白色区域检测到。这些结果表明，由活化的小胶质细胞局部产生的TNF-α可能通过含有死亡结构域的TNF受体1（p55）、半胱天冬酶-2或半胱天冬酶-3活化来选择性地诱导少突胶质细胞死亡，导致白色改变作为主要病理特征。(C)2001 Elsevier Science爱尔兰有限公司和日本神经科学学会。All rights reserved.
We investigated the neuropathological and biochemical changes in the white matter of normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) after bilateral carotid artery ligation (BCAL). One week after BCAL, both WKY and SHR showed white matter rarefaction and vacuolation with reduced oligodendrocytes, but there was no difference between WKY and SHR. On the other hand, vacuoles formed by oligodendroglial cell death were increased significantly from 2 to 4 weeks in the optic tract and fimbria fornix of hypoperfused SHR. Furthermore, terminal deoxynucleotidyl transferase-mediated dUTP in situ nick end labeling (TUNEL)-positive cells and lectin-positive microglia increased in number and intensities of staining more markedly in SHR than in WKY. In situ cell death detection ELISA supported these results quantitatively. RT-PCR represented the expression of TNF-alpha, TNF receptor 1 (p55), caspase-2 (Ich-l) and -3 (CF'P32) mRNAs in both WKY and SHR brains after BCAL. Immunohistochemical analyses revealed that TNF-alpha, TNF receptor 1 (p55), Ich-l and CPP32 immunoreactive cells could also be detected in the white matter regions of hypoperfused SHR. These results suggested that local production of TNF-alpha by the activated microglia might selectively induce oligodendroglial cell death through the death domain-containing TNF receptor 1 (p55), caspase-2 or -3 activation, resulting in white matter changes as a primary pathological feature. (C) 2001 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.