No abstract

The perinatal period, sensitive for newborn survival, is also one of the most critical moments in human brain development. Perinatal hypoxia due to reduced blood supply to the brain (ischemia) is one of the main causes of neonatal mortality. Brain damage caused by perinatal hypoxia–ischemia (HI) can lead to neuro‐ and psychological disorders. However, its impact seems to be region‐dependent, with the hippocampus being one of the most affected areas. Among the neuronal populations of the hippocampus, some interneuron groups – such as somatostatin‐ or neuropeptide Y‐expressing neurons – seem to be particularly vulnerable. The limited information available about the effects of HI in the hippocampus comes mainly from animal models and adult human studies. This article presents an immunohistochemical analysis of somatostatin (SOM) and neuropeptide Y (NPY) expression in the developing human hippocampus after perinatal HI. Two rostrocaudal sections of the body of the hippocampus were analysed, and the number of immunostained cells in the polymorphic layer of the dentate gyrus (DG) and the pyramidal cell layer and stratum oriens of the CA3, CA2 and CA1 fields of the hippocampus proper were quantified. The results showed a lower density of both neuropeptides in hypoxic compared to control cases. In the HI group, the number of SOM‐immunoreactive cell bodies was statistically significantly lower in the pyramidal cell layer and stratum oriens of CA1, while the number of NPY‐expressing neurons was statistically lower in the pyramidal cell layer of CA2. Besides, the number of SOM‐expressing neurons was significantly higher in the stratum oriens of CA1 compared to that in CA2. In sum, we observed a different vulnerability of SOM‐ and NPY‐containing neurons in the developing human hippocampus following perinatal HI damage. Our results could contribute to a better understanding of the behaviour of these neuronal populations under stressful conditions during the perinatal period.

Little information is available on the magnetic resonance imaging (MRI) determination of the hippocampal formation (HF) during the perinatal period. However, this exploration is increasingly used, which requires defining visible HF landmarks on MRI images, validated through histological analysis. This study aims to provide a protocol to identify HF landmarks on MRI images, followed by histological validation through serial sections of the temporal lobe of the samples examined, to assess the longitudinal extent of the hippocampus during the perinatal period. We examined ex vivo MRI images from nine infant control brain samples. Histological validation of the hippocampal formation MRI images was obtained through serial sectioning and examination of Nissl-stained sections at 250 μm intervals along the entire length of the hippocampal formation. Up to six landmarks were identified both in MRI images and the serial histological sections. Proceeding in an anterior to posterior (rostrocaudal) direction, these were as follows: 1) the limen insulae (fronto-temporal junction); 2) the beginning of the amygdaloid complex; 3) the beginning of the lateral ventricle; 4) the caudal limit of the uncus, indicated by the start of the lateral geniculate nucleus (at the level of the gyrus intralimbicus); 5) the end of the lateral geniculate nucleus (beginning of the pulvinar); and 6) the beginning of the fornix. After histological validation of each of these landmarks, the full longitudinal length of the hippocampal formation and distances between landmarks were calculated. No statistically significant differences were found in total length or between landmarks. While the HF is anatomically organized at birth, its annotation is particularly challenging to perform. The histological validation of HF landmarks allows a better understanding of MRI images. The proposed protocol could be useful to assess MRI hippocampal quantification in children and possible variations due to different neurological diseases.