Advances in germinal matrix hemorrhage: Mechanisms, models, and therapeutic targets.

Germinal matrix hemorrhage (GMH) remains a major intracranial complication with significant mortality and lifelong neurodevelopmental deficits in preterm infants. Disruption of the fragile germinal matrix neurovascular unit interferes with the natural course of brain maturation, resulting in both gray and white matter injury as well as persistent motor and cognitive dysfunction. Currently, no disease-modifying therapy is available to reverse established GMH or prevent its long-term neurological sequelae, although several preventive strategies can reduce the risk of hemorrhage in selected clinical contexts. Given the clear need for effective therapeutics, experimental models are essential for elucidating the cellular and molecular mechanisms underlying the etiology and pathophysiological progression of GMH. This review highlights recent preclinical advances in GMH, including its underlying causes and natural history, the development of animal models, and the identification of potential therapeutic targets.