Deferoxamine protects against the development of schizencephaly and motor deficits following neonatal hemorrhagic injury in the mice cerebral cortex.

Schizencephaly is a rare congenital malformation characterized by deep cortical clefts associated with motor deficits and refractory epilepsy. Early hemorrhagic insults frequently precede this condition, triggering cell death involving oxidative stress, neuroinflammation, and ferroptosis. Deferoxamine (DFO), an iron chelator, attenuates damage in adult models of intracerebral hemorrhage; however, its potential to prevent neonatal cortical malformations and their outcomes remains unexplored. This study evaluated the effect of DFO on cortical malformation development, sensory-motor funtion and epileptogenesis following a cryogenic hemorrhagic injury in neonatal mice. Hemorrhage was induced via transcranial freeze injury, followed by intraperitoneal administration of DFO (200 mg/kg) or vehicle (saline) two hours after injury. Motor performance was assessed using the righting reflex test on postnatal days (PND) 5 and 12. Seizure severity and susceptibility were evaluated at PND12 using a modified Racine scale following 50mg/kg pentylenetetrazol (PTZ) systemic administration. Animals were subsequently perfused, and dissected heads underwent magnetic resonance imaging (MRI) to quantify cortical lesion volume using MiPAV software. Preliminary findings showed a significant reduction in righting reflex latency in DFO-treated mice compared with injured vehicle controls at both PND 5 and PND 12. No significant differences were observed between groups in seizure severity or susceptibility. MRI analyses revealed significantly lower cortical lesion volumes in DFO-treated animals compared with saline controls, indicating tissue preservation and neuroprotection following injury. Histochemical analyses will subsequently evaluate cortical iron deposition. In conclusion, DFO attenuates tissue and functional damage, suggesting potential therapeutic implications for preventing brain malformations and their outcomes secondary to neonatal hemorrhagic injury.