Transient focal ischemia results in persistent and widespread neuroinflammation and loss of glutamate NMDA receptors.
Transient focal ischemia results in persistent and widespread neuroinflammation and loss of glutamate NMDA receptors.
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DOI：
10.1016/j.neuroimage.2010.02.073
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发表时间：
2010-06
期刊：
影响因子：
5.7
通讯作者：
Biegon, Anat
中科院分区：
文献类型：
--
作者：
Dhawan, Jasbeer;Benveniste, Helene;Nawrocky, Marta;Smith, S. David;Biegon, Anat
在人类和动物模型中，中风伴有神经炎症。为了检查中风模型中神经炎症和NMDA受体（NMDAR）的时间和解剖学特征，使大鼠（N=17）经历大脑中动脉（MCAO）的90分钟闭塞，并与假手术（N=5）和完整（N=4）对照进行比较。再灌注后24小时通过MRI证实纹状体和部分皮质梗死。在14或30-40天后处死动物，并处理连续冠状冷冻切片，用于神经炎症标记物[3 H] PK 11195和NMDAR拮抗剂[3 H] MK 801的定量放射自显影。在同侧纹状体中观察到[3 H] PK 11195相对于非缺血对照的特异性结合显著增加（>3倍，p<0.0001），无名肿毒（>2倍）较小（20%-80%），但有统计学意义（p=0.002-0.04）部分参与梗死的其他区域（如顶叶和梨状皮质）和侧隔中的同侧增加，与梗塞无关在对侧半球也观察到PBR密度增加的趋势。.在相同的动物，NMDAR特异性结合显着减少双边的隔膜，无名质和腹侧苍白球。在同侧纹状体、中脑、额叶和顶叶皮质也观察到显著降低。这两种现象的不同解剖学分布表明，神经炎症不会引起所观察到的NMDAR减少，尽管在具有强烈神经炎症的同侧区域中NMDAR的损失可能局部增加。.持续性的双侧NMDAR缺失可能反映了受体下调和内化，可能是脑卒中对认知功能的一些影响的原因，而这些影响不能单独用梗死来解释。
Stroke is accompanied by neuroinflammation in humans and animal models. To examine the temporal and anatomical profile of neuroinflammation and NMDA receptors (NMDAR) in a stroke model, rats (N=17) were subjected to 90 minutes occlusion of the middle cerebral artery (MCAO) and compared to sham (N=5) and intact (N=4) controls. Striatal and partial cortical Infarction was confirmed by MRI 24 hr after reperfusion. Animals were killed 14 or 30–40 days later and consecutive coronal cryostat sections processed for quantitative autoradiography with the neuroinflammation marker [3H]PK11195 and the NMDAR antagonist [3H]MK801. Significantly Increased specific binding of [3H]PK11195 relative to non-ischemic controls was observed in the ipsilateral striatum (>3 fold, p<0.0001), susbstantia innominata (>2 fold) with smaller (20%–80%) but statistically significant (p=0.002–0.04) ipsilateral increases in other regions partially involved in the infarct such as the parietal and piriform cortex, and in the lateral septum, which was not involved in the infarct. Trends for increases in PBR density were also observed in the contralateral hemisphere. . In the same animals, NMDAR specific binding was significantly decreased bilaterally in the septum, substantia innominata and ventral pallidum. Significant decreases were also seen in the ipsilateral striatum, accumbens, frontal and parietal cortex. The different anatomical distribution of the two phenomena suggests that neuroinflammation does not cause the observed reduction in NMDAR, though loss of NMDAR may be locally augmented in ipsilateral regions with intense neuroinflammation. . Persistent, bilateral loss of NMDAR, probably reflecting receptor down regulation and internalization, may be responsible for some of the effects of stroke on cognitive function which can not be explained by infarction alone.
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