Adverse neuropsychiatric development following perinatal brain injury: from a preclinical perspective

Abstract

Perinatal brain injury is a leading cause of death and disability in young children. Recent advances in obstetrics, reproductive medicine and neonatal intensive care have resulted in significantly higher survival rates of preterm or sick born neonates, at the price of increased prevalence of neurological, behavioural and psychiatric problems in later life. Therefore, the current focus of experimental research shifts from immediate injury processes to the consequences for brain function in later life. The aetiology of perinatal brain injury is multi-factorial involving maternal and also labour-associated factors, including not only placental insufficiency and hypoxia-ischaemia but also exposure to high oxygen concentrations, maternal infection yielding excess inflammation, genetic factors and stress as important players, all of them associated with adverse long-term neurological outcome. Several animal models addressing these noxious stimuli have been established in the past to unravel the underlying molecular and cellular mechanisms of altered brain development. In spite of substantial efforts to investigate short-term consequences, preclinical evaluation of the long-term sequelae for the development of cognitive and neuropsychiatric disorders have rarely been addressed. This review will summarise and discuss not only current evidence but also requirements for experimental research providing a causal link between insults to the developing brain and long-lasting neurodevelopmental disorders.

Sex-Dependent Effects of Perinatal Inflammation on the Brain: Implication for Neuro-Psychiatric Disorders

“…Significant evidence suggests an interactive effect of fetal sex and perinatal neuroinflammation in the pathogenesis of neurodevelopmental disorders, where factors such as the dose of the immunogen, the gestational timing, and acute versus chronic nature of the immune challenge are important [147]. An array of rodent models have been developed to explore the link between altered neural-immune interactions and ASD and/or other neurodevelopmental disorders.…”

Impact of Brain Injury on Processing of Emotional Prosodies in Neonates

“…This study examined the electrophysiological responses to emotional (fearful and happy) prosody in neonates with and without clinically diagnosed brain injury during the first days following birth (0–10 days), and explored the associations between early ERP signatures in neonates and later neurodevelopment at 30 months of age. As perinatal brain injury is associated with adverse long-term sequelae including cognitive and neuropsychiatric disorders (42) and that the processing of emotion information is a critical social cognition during development, we hypothesized that while healthy neonates could process and show differential MMRs to specific emotions, neonates with brain injuries would exhibit deficits in emotion processing and have altered MMRs compared to healthy controls. Moreover, we aimed to study if any identified early alterations in impaired emotion processing were predictive of cognitive development in later childhood.…”

Treatment with the calcineurin inhibitor and immunosuppressant cyclosporine A impairs sensorimotor gating in Dark Agouti rats

“…Microdialysis studies may therefore extend these initial findings by investigating the exact role of dopamine in distinct brain areas. Given that rodent models have demonstrated cognitive dysfunctions due to aberrant dopaminergic signaling in the medial prefrontal cortex (Castner et al 2004), future studies may also address this issue by analyzing whether immunosuppressive compounds affect working memory in tests such as the radial maze, the Barnes maze, or the Morris water maze (Bendix et al 2019).…”