Infection with the roundworm Angiostrongylus cantonensis is the main cause of eosinophilic meningitis worldwide. The underlying molecular basis of the various pathological outcomes in permissive and non-permissive hosts infected with A. cantonensis remains poorly defined. In the present study, the histology of neurological disorders in the central nervous system (CNS) of infected rats was assessed by using hematoxylin and eosin staining. Quantitative reverse transcription polymerase chain reaction (RT-qPCR), western blot and immunofluorescence (IF) were used in evolutions of the transcription and translation levels of the apoptosis-, necroptosis-, autophagy-, and pyroptosis-related genes. The distribution of apoptotic and necroptotic cells in the rat hippocampus and parenchyma was further detected using flow cytometry, and the features of the ultrastructure of the cells were examined by transmission electron microscopy (TEM). The inflammatory response upon CNS infection with A. cantonensis evolved, as characterized by the accumulation of a small number of inflammatory cells under the thickened meninges, which peaked at 21 days post-infection (dpi) and returned to normal by 35 dpi. The transcription levels and translation of caspase-2, caspase-8, RIP1 and RIP3 increased significantly at 21 and 28 dpi but decreased sharply at 35 dpi compared to those in the normal control group. However, the changes in the expression of caspase-1, caspase-3, caspase-11, Beclin-1 and LC3B were not obvious, suggesting that apoptosis and necroptosis but not autophagy or pyroptosis occurred in the brains of infected animals at 21 and 28 dpi. The results of RT-qPCR, western blot analysis, IF, flow cytometry and TEM further illustrated that necroptosis and caspase-2-mediated apoptosis occurred in astrocytes and neurons but not in microglia in the parenchyma and hippocampus of infected animals. This study provides the first evidence that neuronal and astrocytic necroptosis and caspase-2-mediated apoptosis are induced by A. cantonensis infection in the parenchymal and hippocampal regions of rats at 21 and 28 dpi but these processes are negligible at 35 dpi. These findings enhance our understanding of the pathogenesis of A. cantonensis infection and provide new insights into therapeutic approaches targeting the occurrence of cell death in astrocytes and neurons in infected patients.

中文翻译：

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广州管圆线虫感染引起的大鼠海马和实质的星形胶质细胞和神经元坏死性凋亡和Caspase-2介导的凋亡，但不是小胶质细胞的凋亡。

广州管圆线虫感染是全世界嗜酸性脑膜炎的主要原因。感染广州曲霉的允许和非允许宿主的各种病理结果的潜在分子基础仍然不明确。在本研究中，通过使用苏木精和伊红染色来评估受感染大鼠中枢神经系统（CNS）神经系统疾病的组织学。定量逆转录聚合酶链反应（RT-qPCR）、蛋白质印迹和免疫荧光（IF）用于凋亡、坏死性凋亡、自噬和焦亡相关基因的转录和翻译水平的演变。采用流式细胞术进一步检测大鼠海马及实质中凋亡和坏死细胞的分布，并采用透射电子显微镜（TEM）观察细胞的超微结构特征。广州曲霉感染中枢神经系统后，炎症反应发生演变，其特点是增厚的脑膜下积聚少量炎症细胞，感染后21天达到高峰，35天恢复正常。与正常对照组相比，caspase-2、caspase-8、RIP1和RIP3的转录水平和翻译水平在21和28 dpi时显着增加，但在35 dpi时急剧下降。但caspase-1、caspase-3、caspase-11、Beclin-1和LC3B表达变化不明显，提示感染动物21、28时脑内发生细胞凋亡和坏死性凋亡，而非自噬或焦亡。 dpi。RT-qPCR、western blot分析、IF、流式细胞术和TEM的结果进一步表明，感染动物的实质和海马的星形胶质细胞和神经元中发生了坏死性凋亡和caspase-2介导的细胞凋亡，但小胶质细胞中没有发生。这项研究提供了第一个证据，证明广州曲霉感染在 21 和 28 dpi 时大鼠实质和海马区域会诱导神经元和星形细胞坏死性凋亡以及 caspase-2 介导的细胞凋亡，但这些过程在 35 dpi 时可以忽略不计。这些发现增强了我们对广州曲霉感染发病机制的理解，并为针对感染患者星形胶质细胞和神经元发生细胞死亡的治疗方法提供了新的见解。