The role of inflammation in perinatal brain injury

Abstract

Inflammation is increasingly recognized as being a critical contributor to both normal development and injury outcome in the immature brain. The focus of this Review is to highlight important differences in innate and adaptive immunity in immature versus adult brain, which support the notion that the consequences of inflammation will be entirely different depending on context and stage of CNS development. Perinatal brain injury can result from neonatal encephalopathy and perinatal arterial ischaemic stroke, usually at term, but also in preterm infants. Inflammation occurs before, during and after brain injury at term, and modulates vulnerability to and development of brain injury. Preterm birth, on the other hand, is often a result of exposure to inflammation at a very early developmental phase, which affects the brain not only during fetal life, but also over a protracted period of postnatal life in a neonatal intensive care setting, influencing critical phases of myelination and cortical plasticity. Neuroinflammation during the perinatal period can increase the risk of neurological and neuropsychiatric disease throughout childhood and adulthood, and is, therefore, of concern to the broader group of physicians who care for these individuals.

Third Trimester Brain Growth in Preterm Infants Compared With In Utero Healthy Fetuses

“…9,31,34 Prenatal, intrapartum, and/ or postnatal infections result in inflammatory substances that have been linked to both brain injury and altered brain development in the preterm population. 58,59 In this study, we also report an association between confirmed sepsis and stunted cerebral growth. This specific finding contrasts with 2 other studies, which found no relationship between brain volumes 7 a The estimate of variance explained includes the main effects as well as 2-and 3-way interactions (not shown); all models had a P value < .001.…”

Delayed ALK5 inhibition improves functional recovery in neonatal brain injury

“…3 Given their central role in the production of pro-inflammatory cytokines, reactive oxygen species, matrix metalloproteinases and other cytotoxic molecules, a number of interventions targeted at reducing microglial activation have been tested in pre-clinical models of developmental brain injuries. 1 Reactive astrogliosis also occurs subsequent to brain injuries. Like the microglial reaction, the astroglial reaction is multifaceted.…”

“…The resulting neuroinflammation is regarded as an important contributor to the pathogenetic cascade, contributing to both the initial injury as well as to secondary neurodegeneration. 1 The majority of studies to date have focused on the production of the classic pro-inflammatory cytokines that include IL-1ß, IL-8, IL-18, TNFa and IL-6 as acute increases in these cytokines correlate with penultimate neurological impairments in children surviving perinatal brain injuries. 2 Microglial cells are the principal sentinels of the central nervous system (CNS) and they undergo a rapid transformation to an activated phenotype when the microenvironment of the brain is perturbed.…”

Asociaciones genéticas en la parálisis cerebral; un campo aún en estudio

“…Algunos de los genes más estudiados en la incidencia de paralisis cerebral es el gen para la interleuquina 6 (IL6) es una citoquina pleiotrópica con varias actividades para regular la inflamación, y respuestas de la fase aguda, hematopoyesis, lesión isquémica y desarrollo cerebral 41,42 . Los polimorfismos que involucran la regulación de la expresión de IL6 se han asociado a PC en su mayoría en niños con edad gestacional entre 32-36 semanas.…”