Distinct Pattern of Microglial Response, Cyclooxygenase-2, and Inducible Nitric Oxide Synthase Expression in the Aged Rat Brain After Excitotoxic Damage
Distinct Pattern of Microglial Response, Cyclooxygenase-2, and Inducible Nitric Oxide Synthase Expression in the Aged Rat Brain After Excitotoxic Damage
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DOI：
10.1002/jnr.21751
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发表时间：
2008-11-01
影响因子：
4.2
通讯作者：
Gonzalez, B.
中科院分区：
文献类型：
--
作者：
Campuzano, O.;Castillo-Ruiz, M. M.;Gonzalez, B.
尽管老年人对损伤的反应不同，表现出较差的损伤结果，但对衰老过程中急性损伤的小胶质细胞和炎症反应仍然知之甚少。本研究通过纹状体内注射N-甲基-D-天冬氨酸对成年大鼠(3-4月龄)和老年大鼠(22-24月龄)进行兴奋毒性实验。用凝集素组织化学方法检测小胶质细胞反应，用免疫组织化学和共聚焦分析法检测环氧合酶2(COX2)和诱导型一氧化氮合酶(NOS)的表达。老年损伤动物在损伤后12小时(HPL)表现出更广泛的小胶质细胞反应，在损伤后3天(DPL)小胶质细胞/巨噬细胞密度增加。而年龄较大的反应性小胶质细胞则表现为分支形态和较少的Amoe-boid/圆形。老年损伤组的COX2表达面积减少，但COX2(+)细胞密度明显增加，在最初的24小时内，COX2(+)神经元数量较多，随后出现COX2(+)小胶质细胞/巨噬细胞。而COX2(+)中性粒细胞数量在老年组明显减少。老年损伤纹状体诱导型一氧化氮合酶的诱导速度较快，12hPL时细胞密度较高，主要表达为神经元。从1d开始，老年组iNOS(+)细胞的面积和密度均减少，iNOS(+)神经元、小胶质细胞/巨噬细胞、中性粒细胞和星形胶质细胞的数量减少。综上所述，衰老过程中的兴奋性毒性损伤诱导了不同的小胶质细胞/巨噬细胞反应和炎性酶的表达，这可能解释了老年人损伤结局的变化，并强调了利用老年动物研究急性衰老相关损伤的重要性。(C)2008年Wiley-Liss，Inc.
Microglial and inflammatory responses to acute damage in aging are still poorly understood, although the aged brain responds differently to injury, showing poor lesion outcome. In this study, excitotoxicity was induced by intrastriatal injection of N-methyl-D-aspartate in adult (3-4 months) and aged (22-24 months) rats. Cryostat brain sections were processed for the analysis of microglial response by lectin histochemistry and cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (NOS) expression by immunohistochemistry and confocal analysis. Aged injured animals showed more widespread area of microglial response at 12 hr postlesion (hpl) and greater microglia/macrophage density at 3 days postlesion (dpl). However, aged reactive microglia showed prevalence of ramified morphologies and fewer amoe-boid/round forms. Aged injured animals presented a diminished area of COX2 expression, but a significantly larger density of COX2(+) cells, with higher numbers of COX2(+) neurons during the first 24 hpl and COX2(+) microglia/macrophages later. In contrast, the amount of COX2(+) neutrophils was diminished in the aged. iNOS was more rapidly induced in the aged injured striatum, with higher cell density at 12 hpl, when expression was mainly neuronal. From 1 dpl, both the iNOS(+) area and the density of iNOS(+) cells were reduced in the aged, with lower numbers of iNOS(+) neurons, microglia/macrophages, neutrophils, and astrocytes. In conclusion, excitotoxic damage in aging induces a distinct pattern of microglia/macrophage response and expression of inflammatory enzymes, which may account for the changes in lesion outcome in the aged, and highlight the importance of using aged animals for the study of acute age-related insults. (c) 2008 Wiley-Liss, Inc.