Research Article: Importance of neonatal immunoglobulin transfer for hippocampal development and behaviour in the newborn pig

Date Published: June 28, 2017

Publisher: Public Library of Science

Author(s): Kateryna Goncharova, Liudmyla Lozinska, Ester Arevalo Sureda, Jarosław Woliński, Björn Weström, Stefan Pierzynowski, Antonio Gonzalez-Bulnes.

http://doi.org/10.1371/journal.pone.0180002

Abstract

Neurological disorders are among the main clinical problems affecting preterm children and often result in the development of communication and learning disabilities later in life. Several factors are of importance for brain development, however the role of immunoglobulins (passive immunity transfer) has not yet been investigated. Piglets are born agammaglobulinemic, as a result of the lack of transfer of maternal immunoglobulins in utero, thus, they serve as an ideal model to mimic the condition of immunoglobulin deficiency in preterm infants. Thirty six, unsuckled newborn piglets were fed an infant formula or colostrum and supplemented orally or intravenously with either species-specific or foreign immunoglobulin and then compared to both newborn and sow-reared piglets. Two days after the piglets were born behavioural tests (novel recognition and olfactory discrimination of conspecifics scent) were performed, after which the piglets were sacrificed and blood, cerebrospinal fluid and hippocampi samples were collected for analyses. Both parameters of neuronal plasticity (neuronal maturation and synapse-associated proteins) and behavioural test parameters appeared to be improved by the appearance of species-specific porcine immunoglulin in the circulation and cerebrospinal fluid of the piglets. In conclusion, we postulate possible positive clinical effects following intravenous infusion of human immunoglobulin in terms of neuronal plasticity and cognitive function in preterm infants born with low blood immunoglobulin levels.

Partial Text

Neurological disorders as well as behavioral and neuropsychiatric problems are among the main developmental problems in preterm children which can result in the development of communication and learning disabilities later in life [1]. The pathophysiology leading to the neurodevelopmental problems of premature infants and children is complex [2]. There is increasing evidence that both developing neurons and oligodendrocytes are at risk in the premature brain [3], with the potential to cause gross structural damage or more subtle disruptions in measures of connectivity [4,5,6]. Children born preterm are more likely to have white matter brain abnormalities early on resulting in a higher risk of cognitive dysfunction [7].

All experimental procedures were approved by the Malmö-Lund regional Ethics Review Committee on Animal Experiments (approval № M142-14). All efforts were made to minimize animals’ suffering.

The newborn piglet is generally accepted as a relevant model for human neonates and it is likely that similar factors are involved in the functional maturation of the brain in human newborns. The pig model allows us to assess both structural and functional features of brain development and their regulation by external factors. Moreover, use of the unsuckled neonatal pig model, which is hypogammaglobulinemic at birth, provides us with a possibility to examine the dose-dependency, as well as the species-specificity of immunoglobulin transfer effects on brain development. Thus, in the present study we made use of swine IG in different doses to assess the role of maternal IG transfer in early postnatal development. Moreover, we also tested bovine colostrum which is known to improve intestinal, digestive and immune functions in preterm pigs [32] and is currently being investigated in a clinical pilot trial [33] as the first enteral feeding for preterm infants, to compare the ability of foreign IG to cross the BBB and affect brain development. In the current study, the assessment of functional and structural changes in the hippocampus of the piglets was carried out by investigation of synaptic and neuronal plasticity-associated proteins, as well as measurements of changes in piglet behaviour.

 

Source:

http://doi.org/10.1371/journal.pone.0180002

 

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