# From Brain Organoids to Translational Neurology: Exploring Neuroprotective Targets and Molecular Approaches in Perinatal Brain Injury

## TL;DR

Human brain organoids are being used to study perinatal brain injury and identify new neuroprotective treatments for newborns.

## Contribution

The paper highlights brain organoids as a novel platform for studying PBI and discovering personalized therapies.

## Key findings

- Brain organoids model hypoxic-ischemic and inflammatory insults in human brain development.
- Organoids enable the study of injury-induced changes in neurogenesis and cell interactions.
- Organoids support pharmacogenomic studies for genotype-dependent drug responses in PBI.

## Abstract

Perinatal brain injury (PBI) is a leading cause of long-term neurological deficits in newborns, yet effective therapies are limited. At the cellular level, PBI involves hypoxic–ischemic stress, neuroinflammation, oxidative damage, excitotoxicity, and disrupted neurovascular and glial development. Traditional animal models and 2D cultures cannot fully capture the spatiotemporal complexity of the developing human brain, highlighting the need for more physiologically relevant systems. Human brain organoids have emerged as advanced three-dimensional models that recapitulate region-specific cytoarchitecture, neuronal and glial differentiation, and early circuit formation. They enable modeling of hypoxic–ischemic and inflammatory insults, allowing for the study of injury-induced changes in neurogenesis, gliogenesis, synaptic development, and cell interactions. Organoids facilitate identification of molecular pathways involved in injury and repair, supporting therapeutic target discovery. Using patient-derived induced pluripotent stem cells, organoids also allow personalized pharmacogenomic studies to assess genotype-dependent drug responses and toxicity. Despite limitations such as variability, lack of vascularization and immune components, and ethical considerations, brain organoids offer a promising platform to bridge developmental neurobiology and translational therapeutics, paving the way for targeted and individualized interventions in PBI.