Lehrmann E, Christensen T, Zimmer J, Diemer N H, Finsen B
Pharmabiotec, Department of Anatomy and Cell Biology, Institute of Medical Biology, University of Odense, Odense C, Denmark.
J Comp Neurol. 1997 Sep 29;386(3):461-76.
Transient middle cerebral artery occlusion in rats leads to infarction of the lateral part of the striatum and adjacent neocortex, with selective neuronal necrosis in the bordering penumbral zones. Administration of glutamate, cytokine, and leukocyte antagonists have rescued mainly neocortical neurons, indicating differences in the degenerative processes. The aim of this study was, therefore, to describe the microglial/macrophage activation and polymorphonuclear leukocyte recruitment patterns and to correlate these with the ischemia-induced degenerative processes. The analysis showed significant differences in the characteristics and timing of the microglial/macrophage responses between the caudate putamen and neocortical infarct zones, the infarct zones and their associated penumbral zones, as well as between the striatal and the neocortical penumbral zone. Infiltrations with polymorphonuclear leukocytes into the infarct zones were limited and shortlasting and confined to the acutely degenerating striatum and piriform cortex. A delayed, massive infiltration with lipid phagocytes into the caudate putamen infarct markedly contrasted an early recruitment and activation of microglia/macrophages in the adjacent penumbra. Within the neocortex, a later onset of degeneration along the insular-parietal axis was marked by neuronal expression of heat shock protein and a progressive microglial activation with induction of the full repertoire of microglial activation markers, including a widespread microglial major histocompatibility complex (MHC) class II antigen expression. We interpret the present results as delineating two differentially progressing penumbral zones, which are likely to reflect differences in the underlying degenerative processes. Differences in the microglial/macrophage activation pattern attract special attention, as these cells may constitute specific targets for therapeutic intervention.
大鼠大脑中动脉短暂闭塞会导致纹状体外侧部分及相邻新皮质梗死，在毗邻的半暗带出现选择性神经元坏死。给予谷氨酸、细胞因子和白细胞拮抗剂主要挽救了新皮质神经元，这表明退变过程存在差异。因此，本研究的目的是描述小胶质细胞/巨噬细胞的激活以及多形核白细胞的募集模式，并将这些与缺血诱导的退变过程相关联。分析显示，尾状核壳核与新皮质梗死区、梗死区及其相关半暗带之间，以及纹状体和新皮质半暗带之间，小胶质细胞/巨噬细胞反应的特征和时间存在显著差异。多形核白细胞向梗死区的浸润有限且持续时间短，局限于急性退变的纹状体和梨状皮质。脂质吞噬细胞向尾状核壳核梗死区的延迟大量浸润与相邻半暗带中小胶质细胞/巨噬细胞的早期募集和激活形成明显对比。在新皮质内，沿岛叶 - 顶叶轴的退变较晚开始，其特征为神经元表达热休克蛋白以及小胶质细胞逐渐激活，并诱导出全套小胶质细胞激活标志物，包括广泛的小胶质细胞主要组织相容性复合体（MHC）II类抗原表达。我们将目前的结果解释为描绘了两个进展不同的半暗带，这可能反映了潜在退变过程的差异。小胶质细胞/巨噬细胞激活模式的差异引起了特别关注，因为这些细胞可能构成治疗干预的特定靶点。
