# Clonidine prevents radiation-induced cell death in human brain organoids

## TL;DR

Clonidine, a drug used for high blood pressure, can protect brain cells in human organoids from radiation damage, offering hope for preventing cognitive decline in children undergoing radiotherapy.

## Contribution

This study shows clonidine can reduce radiation-induced damage in human brain organoids, suggesting a potential drug repurposing strategy for pediatric radiotherapy.

## Key findings

- Clonidine reduced radiation-induced loss of neural progenitor and glial cells in brain organoids.
- Clonidine treatment decreased DNA damage and reactive gliosis in irradiated organoids.
- The results suggest pharmacological prevention of radiation neurotoxicity is feasible in human models.

## Abstract

Radiotherapy is a standard treatment of pediatric brain tumors. Though the survival rate has improved for many tumor types, most patients suffer long-term cognitive decline and there is currently no way of preventing radiation-induced damage to healthy brain tissue. Here, we used a human forebrain organoid model to investigate if the α2-adrenoceptor and I1-imidazoline receptor agonist clonidine could prevent radiotoxicity. We found that treatment of organoids with clonidine significantly reduced radiation-induced loss of neural progenitor cells, neurons, astrocytes, and oligodendrocyte lineage cells. Moreover, clonidine reduced overall DNA damage and signs of reactive gliosis in organoids. Our findings demonstrate that pharmacological rescue of radiation neurotoxicity is possible in a human brain organoid model and provides a rationale for future drug repurposing studies aiming to prevent radiation-induced brain injury in children treated with radiotherapy.

The online version contains supplementary material available at 10.1038/s41598-025-26170-2.