Ambrose Natalie, Waters Karen A, Rodriguez Michael L, Bailey Kendall, Machaalani Rita
Department of Medicine and The Bosch Institute, The University of Sydney, Medical Foundation Building K25, Sydney, NSW, 2006, Australia.
Discipline of Pathology, The University of Sydney, Sydney, NSW, 2006, Australia.
Forensic Sci Med Pathol. 2018 Mar;14(1):42-56. doi: 10.1007/s12024-018-9954-1. Epub 2018 Feb 19.
The purpose of this study was to examine the neuronal expression of apoptotic markers in the rostral medulla of a newly characterized dataset of sudden unexpected death in infancy (SUDI), and to determine the impact of diagnostic groupings on these findings and whether they pertain to the intrinsic apoptotic pathway. Immunohistochemical staining was quantified to determine the percentage of neurons positive for active caspase-9 (specific to the intrinsic apoptotic pathway), active caspase-3 (common to the intrinsic and extrinsic apoptotic pathways) and Terminal deoxynucleotidyl transferase mediated dUTP nick-end labelling (TUNEL) (labels DNA fragmentation) in nine nuclei of the rostral medulla. Expression was compared between groups of SUDI infants where the cause of death was initially classified by a forensic pathologist or subsequently after reclassification by an expert panel using the San Diego Criteria. 68 SUDI infants were studied and originally classified as explained SUDI (n = 12), Sudden Infant Death Syndrome (SIDS) (n = 27) and undetermined (n = 29). Reclassification resulted in a decrease in the number of explained SUDI cases to 7 and a decrease in the number of undetermined cases to 4, with a corresponding increase in the number of SIDS cases to 57 (8 SIDS I; 49 SIDS II). The expression of apoptotic markers was similar in explained SUDI and SIDS I infants. However, TUNEL expression was greater in the cuneate (p < 0.001), vestibular (p = 0.01) and hypoglossal (p < 0.001) nuclei and active caspase-3 expression was lower in the arcuate nucleus (p = 0.037) in SIDS II compared to explained Sudden Unexpected Death in Infancy (eSUDI) infants. Compared to SIDS I infants, SIDS II infants had greater TUNEL expression in the dorsal motor nucleus of the vagus (p < 0.01) and greater active caspase-9 expression in the medial and spinal vestibular nuclei (p = <0.01). Changes in apoptotic expression predominated in SIDS II infants. We postulate that these are due to a combination of contributing risk factors including the presence of an upper respiratory tract infection and bed-sharing/co-sleeping. The absence of changes in active caspase-9 expression compared to eSUDI indicates that the intrinsic apoptotic pathway is not upregulated in SIDS.
本研究的目的是检测一组新确定的婴儿猝死综合征（SUDI）病例延髓头端中凋亡标志物的神经元表达情况，确定诊断分组对这些结果的影响，以及它们是否与内源性凋亡途径有关。通过免疫组织化学染色进行定量分析，以确定延髓头端九个核团中活性半胱天冬酶-9（特异性针对内源性凋亡途径）、活性半胱天冬酶-3（内源性和外源性凋亡途径均有）以及末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL，标记DNA片段化）阳性神经元的百分比。在最初由法医病理学家分类死因的SUDI婴儿组与随后由专家小组使用圣地亚哥标准重新分类后的组之间比较表达情况。对68例SUDI婴儿进行了研究，最初分类为原因明确的SUDI（n = 12）、婴儿猝死综合征（SIDS，n = 27）和死因不明（n = 29）。重新分类后，原因明确的SUDI病例数减少至7例，死因不明病例数减少至4例，相应地，SIDS病例数增加至57例（8例SIDS I；49例SIDS II）。原因明确的SUDI婴儿和SIDS I婴儿中凋亡标志物的表达相似。然而，与原因明确的婴儿猝死（eSUDI）婴儿相比，SIDS II婴儿楔束核（p < 0.001）、前庭核（p = 0.01）和舌下神经核（p < 0.001）中的TUNEL表达更高，弓状核中的活性半胱天冬酶-3表达更低（p = 0.037）。与SIDS I婴儿相比，SIDS II婴儿迷走神经背运动核中的TUNEL表达更高（p < 0.01），内侧和脊髓前庭核中的活性半胱天冬酶-9表达更高（p = <0.01）。凋亡表达的变化在SIDS II婴儿中占主导。我们推测这是多种危险因素共同作用的结果，包括上呼吸道感染以及同床/同室睡眠情况。与eSUDI相比，活性半胱天冬酶-9表达无变化表明SIDS中内源性凋亡途径未上调。
