Morphology of the Dentate Gyrus in a Large Cohort of Sudden Infant Deaths—Interrelation Between Features but Not Diagnosis

Abstract

Morphological differences in the dentate gyrus (DG) have been reported in sudden unexpected deaths in infancy (SUDI), with the feature of focal granule cell (GC) bilamination (FGCB) reported as increased in unexplained SUDI, including sudden infant death syndrome (SIDS), compared with explained SUDI (eSUDI). However, it remains to be determined how these morphologies relate to each other and their extent along the anteroposterior length. This retrospective study evaluated the prevalence of FGCB, single or clustered ectopic GCs, granule cell dispersion (GCD), heterotopia, hyperconvolution, gaps, thinning, blood vessel dissection (BVD), and cuffing (BV cuffing), in an Australian SUDI cohort, and compared the prevalence of these features in eSUDI and unexplained SUDI. We analyzed 850 formalin-fixed paraffin-embedded serial and subserial sections of the hippocampus at the level of the lateral geniculate nucleus from 90 infants, and identified GCD in 97% of infants, single ectopic cells, hyperconvolution, thinning, and BVD in 60%-80%, heterotopia in 36%, gaps, clusters of ectopic cells and BV cuffing in 9%–15%, and FGCB in 18%. These features are clustered within 3–5 serial sections. The presence of FGCB correlated with single ectopic GCs and hyperconvolution. There were no differences in the prevalence of these features between unexplained SUDI (n = 74) and eSUDI (n = 16). Our findings highlight that DG morphological features are highly localized, extending 14–35 µm at their focal location(s) along the anteroposterior length. Consequently, multiple sections along the longitudinal extent are required to identify them. No feature differentiated SUDI from eSUDI in our cohort, thus we cannot conclude that any of these features are abnormal and it remains to be determined their functional significance.

Cell death in the lateral geniculate nucleus, and its possible relationship with nicotinic receptors and sudden infant death syndrome (SIDS)

“…Clinical and autopsy characteristics did not differ amongst the diagnostic groups (Table 1 ). Tissue fixation time was higher in the eSUDI group (Table 1 ) as more cases in this group were from an older dataset (early 2000s) when the protocol for fixation time was longer and utilised 10% neutral buffered formalin (NBF) over a few weeks instead of 20% NBF over a few days [ 36 ]. Adjustment was made for the impact of fixation time on Casp-3 expression (data not shown).…”

“…Tissue collection and staining were performed in our laboratory as detailed previously [32] and the same tissue sections were evaluated in our reports focused on the hippocampus in these infants [11][12][13]36]. From stained tissue sections of 52 infants, a subgroup of 43 infants had tissue sections suitable for the current study based on the presence of the LGN at the correct level.…”

Early Postnatal Exposure to Intermittent Hypercapnic Hypoxia (IHH), but Not Nicotine, Decreases Reelin in the Young Piglet Hippocampus

“…The following morphological features of the DG (Blümcke et al 2009;Kinney et al 2015;Machaalani et al 2021) and CA1 (Kinney et al 2015) were sought on microscopic examination: GCD, focal granule cell bilamination, blood vessels in the GCL and SP, and gaps in the SP layer. Our terminology of external and internal limbs of the DG were applied as defined by Blümcke et al (2009) and Machaalani et al (2021).…”