Neonatal hypoxia-ischemia: cellular and molecular brain damage and therapeutic modulation of neurogenesis

Perinatal asphyxia remains a major cause of both mortality and neurological morbidity. Neonatal encephalopathy affects to 1-3/1,000 newborns, leading to significant brain damage and childhood disability. The only standard therapy is moderate hypothermia, whose efficacy, despite proved, is limited, being partially effective. The capacity of hypothermia in promoting cell proliferation in the neurogenic niches of the central nervous system remains subject of investigation. The use of therapeutic agents such as erythropoietin and cannabinoids and mesenchymal stem cells have shown promising results in experimental models of perinatal asphyxia, being able of modulate neurogenesis, neuronal plasticity and neuroreparation processes after hypoxic-ischemic brain injury. The effects of these therapies in clinics are still unknown, so as if the newborn cells will be able to effectively integrate in the existing neuronal networks or if they will develop their proper functions in a brain-damaged microenvironment, thus being necessary new works focused on the evaluation of the real potential of these therapies in the modulation of neurogenesis after neonatal hypoxia-ischemia.