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Neuroscience. 2014 Jun 20;271:77-98. doi: 10.1016/j.neuroscience.2014.04.018. Epub 2014 Apr 26.

Developmental study of the distribution of hypoxia-induced factor-1 alpha and microtubule-associated protein 2 in children's brainstem: comparison between controls and cases with signs of perinatal hypoxia.

Author information

1
Instituto de Neurociencias de Castilla y León (INCYL), Laboratorio de Neuroanatomía de los Sistemas Peptidérgicos, c/ Pintor Fernando Gallego 1, University of Salamanca, 37007 Salamanca, Spain.
2
Neurobiología Celular y Química Molecular, Facultades de Medicina y Farmacia, Universidad de Castilla-La Mancha, Avenida de Almansa 14, 02006 Albacete, Spain.
3
Servicio de Anatomía Patológica, Hospital Virgen del Rocío, Avenida Manuel Siurot s/n, 41013 Sevilla, Spain.
4
Neurobiología Celular y Química Molecular, Facultades de Medicina y Farmacia, Universidad de Castilla-La Mancha, Avenida de Almansa 14, 02006 Albacete, Spain; Kavli Institute for Systems Neuroscience, Center for Neural Computation, Norwegian University for Sciences and Technology (NTNU), Trondheim, Norway.
5
Laboratorio de Neuroanatomía Humana, Facultad de Medicina de Albacete, Universidad de Castilla-La Mancha, Centro Regional de Investigaciones Biomédicas (CRIB), Avenida de Almansa 14, 02006 Albacete, Spain.
6
Neurobiología Celular y Química Molecular, Facultades de Medicina y Farmacia, Universidad de Castilla-La Mancha, Avenida de Almansa 14, 02006 Albacete, Spain. Electronic address: Pilar.Marcos@uclm.es.

Abstract

Perinatal asphyxia and hypoxia are common causes of morbidity in neonates. Prenatal birth associated with hypoxemia often results in several disorders because of the lack of oxygen in the brain. Survival rates from perinatal hypoxia have improved, but appropriate treatments for recovery are still limited, with great impact on patients, their families, society in general and health systems. The aim of this work is to contribute to a better understanding of the cellular mechanisms underlying the brainstem responses to hypoxia. For this purpose, distributions of two proteins, hypoxia-inducible factor-1 alpha (HIF-1α) and microtubule-associated protein 2 (MAP-2) were analyzed in brainstems of 11 children, four of them showing neuropathological evidence of brain hypoxia. They were included in control or hypoxic groups, and then in several subgroups according to their age. Immunohistochemical labeling for these proteins revealed only cell bodies containing HIF-1α, and both cell bodies and fibers positive for MAP-2 in the children's brainstems. The distribution of HIF-1α was more restricted than that of MAP-2, and it can be suggested that the expression of HIF-1α increased with age. The distribution pattern of MAP-2 in the medulla oblongata could be more due to age-related changes than to a response to hypoxic damage, whereas in the pons several regions, such as the nucleus ambiguus or the solitary nucleus, showed different immunolabeling patterns in controls and hypoxic cases. The distribution patterns of these two proteins suggest that some brainstem regions, such as the reticular formation or the central gray, could be less affected by conditions of hypoxia.

KEYWORDS:

HIF-1α; MAP-2; brainstem; children; hypoxia; immunohistochemistry

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