Neuropeptides in the developing human hippocampus under hypoxic–ischemic conditions

• Published in: Journal of anatomy Vol. 239; no. 4; pp. 856 - 868
• Main Authors: González Fuentes, Joaquín, Insausti Serrano, Ricardo, Cebada Sánchez, Sandra, Lagartos Donate, Maria José, Rivas Infante, Eloy, Arroyo Jiménez, María del Mar, Marcos Rabal, María del Pilar
• Format: Journal Article
• Language: English
• Published: Oxford Wiley Subscription Services, Inc 01-10-2021; John Wiley and Sons Inc
• Subjects: Animal models; brain development; Brain injury; Dentate gyrus; Hippocampus; Hypoxia; hypoxia–ischemia; Ischemia; Neonates; Neurons; Neuropeptide Y; Neuropeptides; Original Paper; Original Papers; Somatostatin
• ISSN: 0021-8782; 1469-7580
• DOI: 10.1111/joa.13458

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.
Hypoxia‐ischemia during the perinatal period could damage the hippocampal interneuron populations which might lead to the appearance of different problems during subsequent development. Interneurons containing Somatostatin and Neuropeptide Y located in the hippocampal ammonic fields are affected differently, although there is a global reduction after suffering perinatal hypoxia‐ischemia. This work is the first study that describes this issue in depth in the developmental human hippocampus.