Cytokine immunoreactivity in cortical and subcortical neurons in periventricular leukomalacia:: are cytokines implicated in neuronal dysfunction in cerebral palsy?
Cytokine immunoreactivity in cortical and subcortical neurons in periventricular leukomalacia:: are cytokines implicated in neuronal dysfunction in cerebral palsy?
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DOI：
10.1007/s00401-002-0633-6
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发表时间：
2003-03-01
影响因子：
12.7
通讯作者：
Sébire, G
中科院分区：
文献类型：
--
作者：
Kadhim, H;Tabarki, B;Sébire, G
脑性瘫痪(CP)的主要神经病理基础是脑室周围白质软化(PVL)的一种白质(WM)损伤。前炎性细胞因子最近被证明与PVL的发病有关。许多PVL患者出现皮质和深部灰质神经元功能障碍，如癫痫、认知障碍和锥体外系障碍。西医损害和随后的神经元紊乱之间的确切关系的性质尚不清楚。在实验模型中，细胞因子被证明具有神经毒性。这增加了研究细胞因子对神经元皮质发育的可能有害影响的必要性。应用原位免疫组织化学方法检测了22例PVL患儿(研究组)和22例非PVL患儿(对照组)大脑皮质和灰质神经元中细胞因子(TNF-α、IL-1β、IL-6)的免疫反应。虽然PVL脑的皮质和其他神经元结构未显示明显的病理异常，但在新皮质、海马、基底节和丘脑的许多神经元中检测到强烈的细胞因子免疫反应。然而，细胞因子的标记存在地区差异。此外，肿瘤坏死因子-α的表达多于IL-1β，IL-6呈阴性反应。相比之下，“对照”大脑中神经元细胞因子的标记可以忽略不计。综上所述，我们首次报道和描述了PVL皮质和深灰质神经元中促炎症细胞因子的原位免疫反应。这些发现可能提供了对与PVL相关的智力缺陷和其他皮质和深灰质神经元功能障碍的神经解剖学相关性的洞察。
The major neuropathological substrate associated with cerebral palsy (CP) is a form of white matter (WM) injury known as periventricular leukomalacia (PVL). Proinflammatory cytokines were recently shown to be implicated in PVL pathogenesis. Many PVL patients develop cortical and deep gray neuronal dysfunctions such as epilepsy, cognitive deficits and extrapyramidal disorders. The precise nature of the relationship between the WM lesion and the subsequent neuronal disorders is unclear. Cytokines were shown to exert neurotoxicity in experimental models. This raises the need to investigate a possible noxious effect by cytokines on neuronal cortical development. In situ immunohistochemical methods were applied on 22 brains from infants both with PVL (study group) and without PVL (control group) to detect any immunoreactivity for cytokines (TNF-alpha, IL-1beta, IL-6) in cortical and gray matter neurons. While cortical and other neuronal structures in PVL brains did not display noticeable pathological anomalies, strong cytokine immunoreactivity was detected in many neurons in the neocortex, hippocampus, basal ganglia and thalamus. There were, however, regional differences in cytokine labeling. In addition, there was more TNF-alpha staining than IL-1beta; IL-6 was negative. In contrast, neuronal cytokine labeling in the "control" brains was negligible. In conclusion, we report and characterize, for the first time, the in situ immunoreactivity for proinflammatory cytokines in cortical and deep gray neurons in PVL. These findings might provide insights into the neuro-anatomical correlate for the intellectual deficits and the other cortical and deep gray neuronal dysfunctions associated with PVL.