Aromatase and neuroinflammation in rat focal brain ischemia
Aromatase and neuroinflammation in rat focal brain ischemia
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大鼠局灶性脑缺血中的芳香酶和神经炎症
DOI：
10.1016/j.jsbmb.2017.09.019
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发表时间：
2017-11
影响因子：
4.1
通讯作者：
Biegon Anat
中科院分区：
文献类型：
--
作者：
Zhong Yu H.;Dhawan Jasbeer;Kovoor Joel A.;Sullivan John;Zhang Wei X.;Choi Dennis;Biegon Anat
越来越多的证据表明，芳香化酶的表达，负责雄激素转化为雌激素，是短暂上调大鼠中风模型。进一步表明芳香酶表达增加与神经炎症有关，并且它在女性中具有神经保护作用。我们的目标是研究芳香化酶上调实验性中风的关系，神经炎症，梗死和不同的假定的神经保护剂治疗的雄性大鼠。对完整雄性大鼠进行短暂（90分钟）大脑中动脉闭塞（MCAO），并在再灌注后立即注射selfotel（N-甲基-d-天冬氨酸（NMDA）受体竞争性拮抗剂）、TPEN（锌螯合剂）、两种药物的组合或溶媒。在MCAO后14天处死动物，连续脑切片用于测量芳香化酶表达、脑梗死体积和神经炎症。定量免疫组织化学（IHC）显示，相对于对侧病灶区域，梗死周围区域脑芳香化酶表达增加，神经保护剂可部分消除。梗死周围区芳香化酶表达与梗死体积之间无相关性，而梗死体积可被神经保护剂降低。通过定量放射自显影测量的小胶质细胞活化与梗死呈正相关，与梗死周围区芳香化酶表达呈负相关。我们的研究结果表明，局灶性缺血上调脑芳香化酶在雄性大鼠脑手术后14天，这是在时间范围内记录的女性。然而，芳香化酶的表达和梗死体积之间缺乏负相关性，小胶质细胞增生和芳香化酶之间缺乏正相关性，不支持芳香化酶作为神经保护介质的主要作用，或在男性局灶性缺血中小胶质细胞活化和芳香化酶表达增加之间的因果关系。
Accumulating evidence suggests that expression of aromatase, the enzyme responsible for the conversion of androgens to estrogens, is transiently upregulated in rat stroke models. It was further suggested that increased aromatase expression is linked to neuroinflammation and that it is neuroprotective in females. Our goal was to investigate aromatase upregulation in male rats subjected to experimental stroke in relationship to neuroinflammation, infarct and response to treatment with different putative neuroprotective agents. Intact male rats were subjected to transient (90 min) middle cerebral artery occlusion (MCAO) and administered selfotel (N-methyl-d-aspartic acid (NMDA) receptor competitive antagonist), TPEN (a zinc chelator), a combination of the two drugs or vehicle, injected immediately after reperfusion. Animals were killed 14 days after MCAO and consecutive brain sections used to measure aromatase expression, cerebral infarct volume and neuroinflammation. Quantitative immunohistochemistry (IHC) demonstrated increased brain aromatase expression in the peri-infarct area relative to contralesional area, which was partially abrogated by neuroprotective agents. There was no correlation between aromatase expression in the peri-infarct zone and infarct volume, which was reduced by neuroprotective agents. Microglial activation, measured by quantitative autoradiography, was positively correlated with infarct and inversely correlated with aromatase expression in the peri-infarct zone. Our findings indicate that focal ischemia upregulates brain aromatase in the male rat brain at 14 days post surgery, which is within the time frame documented in females. However, the lack of negative correlation between aromatase expression and infarct volume and lack of positive correlation between microgliosis and aromatase do not support a major role for aromatase as a mediator of neuroprotection or a causal relationship between microglial activation and increased aromatase expression in male focal ischemia.
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影响因子：
4.8
作者：
C. Roselli
通讯作者：
C. Roselli
影响因子：
9.3
作者：
Pérez-Álvarez MJ;Maza Mdel C;Anton M;Ordoñez L;Wandosell F
通讯作者：
Wandosell F
影响因子：
4.7
作者：
Hammond, J;Le, Q;LeBlanc, A
通讯作者：
LeBlanc, A
DOI：
10.1016/s0749-4041(08)79111-5
发表时间：
2009
期刊：
Yearbook of Vascular Surgery
影响因子：
--
作者：
G. Moneta
通讯作者：
G. Moneta
影响因子：
2.7
作者：
Roselli CE;Liu M;Hurn PD
通讯作者：
Hurn PD