Targeting Ferroptosis and PANoptosis to Prevent Brain Injury after Intraventricular Hemorrhage

Intraventricular hemorrhage is one of the most serious comorbidities of prematurity and is associated with long-term neurological deficits, and there are currently no widely accepted treatments.

This project aims to determine the mechanisms regulating neural cell death and to identity the master molecular regulators of the common cell death commitment point in order to support the development of novel and effective treatment strategies targeting secondary injury after hemorrhage.

The ultimate goal is to reduce the incidence of neurological disability in preterm infants.We will use cell culture and animal models to study the regulated cell death and secondary brain injury after intraventricular hemorrhage.

Specifically, we will 1) identify the mitochondria-related master molecular regulators of ferroptosis and PANoptosis in IVH; 2) determine the impact of microglia activation and glia-neuron interactions on ferroptosis, PANoptosis, and brain injury after IVH; and 3) explore the potential and possible mechanisms of stem cell therapy to ameliorate ferroptosis, PANoptosis, and brain injury in IVH.The mechanistic insights into preterm hemorrhagic brain injury gained from these investigations will ultimately lead to the development of novel interventions and repair strategies for reducing neurological handicaps and improving the quality of life of patients with perinatal hemorrhagic brain injury.