Reduced Expression of Excitatory Amino Acid Transporter 2 and Diffuse Microglial Activation in the Cerebral Cortex in AIDS Cases With or Without HIV Encephalitis
Reduced Expression of Excitatory Amino Acid Transporter 2 and Diffuse Microglial Activation in the Cerebral Cortex in AIDS Cases With or Without HIV Encephalitis
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DOI：
10.1097/nen.0b013e31819715df
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发表时间：
2009-02-01
影响因子：
3.2
通讯作者：
Izumo, Shuji
中科院分区：
文献类型：
--
作者：
Xing, Hui Qin;Hayakawa, Hitoshi;Izumo, Shuji
为了确定人类免疫缺陷病毒1型脑炎(HIVE)与获得性免疫缺陷综合征痴呆复合体中弥漫性脊灰营养不良的关系，我们对11例有HIV1感染和9例无HIVE感染的HIV-1感染者的脑组织标本进行了神经病理学检查。大脑没有机会性疾病和重大脑血管病变。两组均可见弥漫性小胶质细胞活化，星形胶质细胞增多，兴奋性氨基酸转运体2(EAAT-2)免疫反应减弱。这些变化与脑炎的严重程度或p24免疫染色检测到的局部HIV-1感染无关。部分活化的小胶质细胞表达EAAT-2，IL-1β和肿瘤坏死因子仅在蜂窝组织的小胶质细胞结节中表达，而在弥漫性活化的小胶质细胞区域不表达。在EAAT-2降低的病例中，EAAT-2的表达面积与激活的小胶质细胞数量呈显著负相关(p<；0.01)。这些数据表明，在获得性免疫缺陷综合征患者中，弥漫性皮质改变可能独立于蜂窝而发生。激活的小胶质细胞表达EAAT-2提示它们可能发挥代偿作用，保护神经元免受谷氨酸的神经毒性。
To determine the relationship between the human immunodeficiency virus type 1 (HIV-1) encephalitis (HIVE) and diffuse polio-dystrophy in the acquired immunodeficiency syndrome dementia complex, we examined the neuropathologic features in brain autopsy tissue specimens of HIV-1-infected patients with (n = 11) or without HIVE (n = 9). The brains were free of opportunistic diseases and major cerebrovascular lesions. In both groups, there was diffuse microglial activation, astrocytic gliosis, and decreased excitatory amino acid transporter 2 (EAAT-2) immunoreactivity. These changes did not correlate either with the severity of encephalitis or local HIV-1 infection as detected by p24 immunostaining. Some activated microglia expressed EAAT-2; interleukin-1 beta and tumor necrosis factor were detected only in microglial nodules of HIVE cases but not in areas with diffusely activated microglia. There was a significant negative correlation between the areas of EAAT-2 expression and numbers of activated microglia (p < 0.01) in cases with decreased EAAT-2. These data indicate that diffuse cortical changes may occur independently of HIVE in acquired immunodeficiency syndrome patients. The expression of EAAT-2 by activated microglia suggests that they might exert a compensatory effect that protects neurons from glutamate neurotoxicity.