Cell Death in the Human Infant Central Nervous System and in Sudden Infant Death Syndrome (SIDS)

Overview

Journal Apoptosis

Publisher Springer

Date 2019 Jan 3

PMID 30600425

Citations 6

Authors

Natalie Ambrose

Michael Rodriguez

Karen A Waters

Rita Machaalani

Affiliations

Soon will be listed here.

Abstract

The brainstem has been a focus of sudden infant death syndrome (SIDS) research with amassing evidence of increased neuronal apoptosis. The present study extends the scope of brain regions examined and determines associations with known SIDS risk factors. Immunohistochemical expression of cell death markers, active caspase-3 and TUNEL, was studied in 37 defined brain regions in infants (aged 1-12 months) who died suddenly and unexpectedly (SUDI). A semi-quantitative mean score of marker expression was derived for each region and scores compared between three SUDI subgroups: explained SUDI (eSUDI; n = 7), SIDS I (n = 8) and SIDS II (n = 13). In eSUDI, active caspase-3 scores were highest in several nuclei of the rostral medulla, and lowest in the hypothalamus and cerebellar grey matter (GM). TUNEL was highest in regions of the hippocampus and basal ganglia, and lowest in the thalamus and cerebellar GM. TUNEL scores were higher in SIDS II compared to eSUDI in the amygdala (p = 0.03) and 5/9 nuclei in the rostral medulla (p = 0.04 - 0.01), and higher in SIDS II compared to SIDS I in the amygdala (p < 0.01), putamen (p = 0.01), lentiform nucleus (p = 0.03) and parietal (p = 0.03) and posterior frontal (p = 0.02) cortex. Active caspase-3 was greater in the hypoglossal nucleus (p = 0.03) of SIDS I compared to eSUDI infants. Co-sleeping, cigarette smoke exposure and the presence of an upper respiratory tract infection in SIDS infants was associated with differences in marker expression. This study affirms the sensitivity of the brainstem medulla to cell death in SIDS, and highlights the amygdala as a new region of interest.

Citing Articles

Focal granule cell bilamination of the dentate gyrus-its prevalence across the human age spectrum and review of the literature.

Machaalani R, Rodriguez M, Vivekanandarajah A J Neuropathol Exp Neurol. 2024; 84(1):22-33.

PMID: 39468770 PMC: 11659596. DOI: 10.1093/jnen/nlae109.

Known pathogenic gene variants and new candidates detected in sudden unexpected infant death using whole genome sequencing.

Bard A, Clark L, Cosgun E, Aldinger K, Timms A, Quina L Am J Med Genet A. 2024; 194(11):e63596.

PMID: 38895864 PMC: 11706325. DOI: 10.1002/ajmg.a.63596.

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

Chang C, Vivekanandarajah A, Waters K, Machaalani R Mol Neurobiol. 2023; 60(7):4120-4131.

PMID: 37041306 PMC: 10224858. DOI: 10.1007/s12035-023-03332-9.

Comparative analysis of four nuclei in the human brainstem: Individual differences, left-right asymmetry, species differences.

Baizer J, Witelson S Front Neuroanat. 2023; 17:1069210.

PMID: 36874056 PMC: 9978016. DOI: 10.3389/fnana.2023.1069210.

Individual variability in the size and organization of the human arcuate nucleus of the medulla.

Baizer J, Webster C, Witelson S Brain Struct Funct. 2021; 227(1):159-176.

PMID: 34613435 DOI: 10.1007/s00429-021-02396-4.

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