Retrospective Case-Control Study of Apolipoprotein J/Clusterin Protein Expression in Early Liveborn Neonatal Deaths with and without Pontosubicular Necrosis
Aims. Our objective was to examine Apo J protein expression in a total of 27 early liveborn neonatal deaths (less than 7 days of age) selected from the Scottish Perinatal Study (gestation of 25–42 weeks) comparing a group with histological pontosubicular necrosis (PSN) ( ) to a control group lacking PSN ( ). Methods. Using immunohistochemistry we evaluated postmortem pons and hippocampus from patients with PSN versus controls. Results. In the group with PSN, 11/12 (92%) cases showed positive Apo J neurones in the hippocampus/pons compared with 6/15 (40%) cases without PSN ( , odds ratio 27.5, 95% confidence interval 2.881–262.48, using exact logistic regression)—independent of gestation, presence or absence of clinical asphyxia, duration of labour, or postnatal age. Clinical asphyxia was present in 10/15 (67%) without PSN compared with 11/12 (92%) with PSN. Neuronal Apo J positivity was present in 15/21 (71%) of clinically asphyxiated cases compared with 2/6 (33%) of the cases with no evidence of clinical asphyxia ( , odds ratio 5, 95% confidence interval 0.71 to 34.94). Conclusions. Apo J neuronal protein expression is significantly increased in cases with PSN compared to cases without PSN—independent of gestation, presence of clinical asphyxia, duration of labour, or postnatal age. 1. Introduction Apolipoprotein J (Apo J), (also known as clusterin, serum protein 40, cytolysis inhibitor CLI, glycoprotein III, sulfated glycoprotein 2 SGP 2, or testosterone repressed prostate message 2, TRPM-2) was first identified from chromaffin granules of the bovine adrenal medulla and in the ram rete testis [1, 2]. Like Apolipoprotein E, it is expressed in the brain in a number of physiological and pathological conditions [3]. Apo J has been implicated in cell-cell interactions, lipid transport, inhibition of complement-mediated cell lysis, secretion, hypoxic/ischaemic encephalopathy, epilepsy, apoptosis, and neurodegeneration [4–12]. A truncated intracellular form that lacks the signal peptide for processing in the endoplasmic reticulum has also been described [13]. At a molecular level, Han et al. have shown in an experimental animal model of HI that Apo J accumulates in dying neurones and that Apo J-null mice suffered 50% less brain injury compared with wild-type mice subjected to HI (hypoxic/ischaemic) insults [14]. Pontosubicular necrosis (PSN) describes the association on histology between hypoxic death of neurones in the ventral pons and the subiculum in human neonates. Experimental studies have shown that the mode of death in these neurons is apoptosis [15].
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