Neurological consequences of systemic inflammation in the premature neonate

Abstract

Despite substantial progress in neonatal care over the past two decades leading to improved survival of extremely premature infants, extreme prematurity continues to be associated with long term neurodevelopmental impairments. Cerebral white matter injury is the predominant form of insult in preterm brain leading to adverse neurological consequences. Such brain injury pattern and unfavorable neurologic sequelae is commonly encountered in premature infants exposed to systemic inflammatory states such as clinical or culture proven sepsis with or without evidence of meningitis, prolonged mechanical ventilation, bronchopulmonary dysplasia, necrotizing enterocolitis and chorioamnionitis. Underlying mechanisms may include cytokine mediated processes without direct entry of pathogens into the brain, developmental differences in immune response and complex neurovascular barrier system that play a critical role in regulating the cerebral response to various systemic inflammatory insults in premature infants. Understanding of these pathologic mechanisms and clinical correlates of such injury based on serum biomarkers or brain imaging findings on magnetic resonance imaging will pave way for future research and translational therapeutic opportunities for the developing brain.

The value of clinical examination in preterm newborns after neonatal sepsis: a case control study.

“…[25] This is because axonal tracts are more affected by the systemic inflammatory process rather than infectious agents itself. [5] However, the PTNBs with late sepsis had worse performances in the HNNE movements and behavior categories, with significant results and with a tendency to the significance of tone, tone patterns and reflexes. The prominent role of this type of sepsis in neurological dysfunctions was evidenced by a French developmental follow-up study, consisting of 139 PTNBs, which compared the frequency of CP at five years of age among those with early and late sepsis.…”

“…[21] The frequent neurological abnormalities found in PTNBs after a septic episode are due to the systemic inflammatory response associated with the extreme vulnerability of the developing brain in the neonatal period. [5] The lesion mechanism begins with increased pro-inflammatory cytokines, which easily cross the blood-brain barrier, striking the glial cells, causing hypomyelination and possible cerebral white matter lesions, besides inducing neuronal apoptosis and impairing differentiation of neurons and cerebral blood flow, favoring the occurrence of ischemic and hemorrhagic events. [2,4] Clinical studies with neuroimaging evidence brain lesions in these PTNBs.…”

“…Since the systemic inflammatory response is a significant risk factor for white matter lesions that are characterized by cystic periventricular leukomalacia (PVL). [4,5] Several clinical studies have established through neuroimaging the association between neonatal infections and brain axonal lesions in PTNBs. [2,[6][7][8][9] This neuronal damage may result in neurodevelopmental impairment in these children.…”

Inflammatory molecules and neurotrophic factors as biomarkers of neuropsychomotor development in preterm neonates: A Systematic Review

“…The association between a pro-inflammatory profile and poor cognitive and motor development is not completely elucidated. One of the possible explanations is that inflammatory molecules, including cytokines, are able to cross the compromised blood-brain barrier and to activate the microglia (Kelley et al, 2017;Patra et al, 2017). This might induce neuronal and glial cell apoptosis, therefore interfering in axonal growth and myelin sheath formation (Burd et al, 2012;Guo et al, 2010;Jenster et al, 2014).…”

Monocyte-derived macrophages for treatment of cerebral palsy: a study of 57 cases

“…In both cases, inflammation is considered the leading pathogenic factor that induces neural cell damage. [5][6][7] Convincing evidence has been obtained pointing to the association between inflammation and neonatal encephalopathy. [8][9][10] Moreover, striking improvement in motor function following reduction of neuroinflammation in a rabbit model of CP demonstrates the key role of inflammation in the pathophysiology of CP.…”