Background and aims
Necrotizing enterocolitis (NEC) in preterm infants is associated with
neurodevelopmental delay and cerebral palsy. We hypothesized that intestinal
NEC lesions affect inflammatory cytokines in cerebrospinal fluid
(CSF) which in turn may affect neurite differentiation.
Methods
Variable degrees of NEC lesions developed spontaneously in piglets
reared for 9 days after preterm birth. CSF samples were collected and
cytokine profile was evaluated by multiplex cytokine array ELISA.
Hippocampal structures were dissected and cytokine mRNAs were measured
by qPCR. The ability of piglet CSF to promote neurite outgrowth
was quantified by stereology using primary rat hippocampal neurons
in vitro.
Results
Relative to healthy controls, pigs with NEC lesions in either intestine or
colon showed altered concentrations for 7 of 32 cytokines in CSF and
higher neurite outgrowth in the in vitro neuronal differentiation model.
The qPCR analyses showed higher erythropoietin mRNA in the hippocampus
of NEC pigs.
Conclusions
Intestinal NEC lesions affect CSF cytokine profile in preterm pigs and
this may affect the differentiation of neurons in the brain. Neuronal plasticity
in immature brain may explain that NEC lesions, via changes in
CSF cytokine levels, may affect neurodevelopment in preterm neonates