Intranasal osteopontin for rodent germinal matrix hemorrhage

Germinal matrix hemorrhage (GMH) is the most common and devastating neurological problem of premature infants. Current treatment is largely ineffective and GMH has been nonpreventable. Osteopontin (OPN) is an endogenous protein that has been shown to be neuroprotective, however, it has not been tested in GMH. P7 neonatal rats were subjected to stereotactic ganglionic eminence collagenase infusion. Groups were as follows: (1) sham, (2) GMH + vehicle, (3) GMH + intranasal OPN. Seventy-two hours later, the animals were evaluated using righting reflex, blood-brain barrier (BBB) permeability by Evans blue dye leakage, brain water content, and hemoglobin assay. Intranasal OPN improved outcomes after GMH by attenuation of brain swelling, BBB function, re-bleeding, and neurological outcomes. OPN may play an important role in enhancing neuroprotective brain signaling following GMH. These observed effects may offer novel possibilities for therapy in this patient population.