Medical Department, Brookhaven National Laboratory, Building 490, Upton, NY 11973, USA.
Neuroimage. 2010 Jun;51(2):599-605. doi: 10.1016/j.neuroimage.2010.02.073. Epub 2010 Mar 4.
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 a 90 min occlusion of the middle cerebral artery (MCAO) and compared to sham (N=5) and intact (N=4) controls. Striatal and parietal cortical infarction was confirmed by MRI 24h after reperfusion. Animals were killed 14 or 30-40 days later and consecutive coronal cryostat sections were processed for quantitative autoradiography with the neuroinflammation marker [(3)H]PK11195 and the NMDAR antagonist [(3)H]MK801. Significantly increased specific binding of [(3)H]PK11195 relative to non-ischemic controls was observed in the ipsilateral striatum (>3 fold, p<0.0001), substantia 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 cannot be explained by infarction alone.
中风伴随着人类和动物模型中的神经炎症。为了研究中风模型中的神经炎症和 NMDA 受体（NMDAR）的时间和解剖学特征，将 17 只大鼠进行 90 分钟的大脑中动脉闭塞（MCAO），并与假手术（n=5）和完整(n=4)对照组进行比较。再灌注后 24 小时通过 MRI 确认纹状体和顶叶皮质梗塞。14 或 30-40 天后处死动物，并对连续冠状冷冻切片进行神经炎症标志物[(3)H]PK11195和 NMDAR 拮抗剂[(3)H]MK801的定量放射自显影处理。与非缺血对照相比，同侧纹状体[(3)H]PK11195的特异性结合显著增加（>3 倍，p<0.0001），同侧壳核（>2 倍）也有较小（20%-80%）但统计学上显著（p=0.002-0.04）的增加，其他部分与梗塞相关的区域如顶叶和梨状皮质，以及外侧隔核也有增加，但不参与梗塞。在对侧半球也观察到 PBR 密度增加的趋势。在同一动物中，NMDAR 特异性结合在隔核、壳核和腹侧苍白球双侧均显著降低。同侧纹状体、伏隔核、额皮质和顶叶皮质也出现显著减少。两种现象的不同解剖分布表明，神经炎症不会导致观察到的 NMDAR 减少，尽管在同侧具有强烈神经炎症的区域，NMDAR 的损失可能局部增加。持续的双侧 NMDAR 丧失，可能反映受体下调和内化，可能是中风对认知功能的一些影响的原因，这些影响不能仅用梗塞来解释。
