Neuroprotective effect of nipradilol, an NO donor, on hypoxic–ischemic brain injury of neonatal rats

Hypoxia–ischemia is a common cause of neonatal brain injuries. Nitric oxide (NO) is upregulated in the brain after hypoxia–ischemia and generally believed to exert a paradoxical effect on neurons, neurodestruction and neuroprotection, but it has not been demonstrated that NO is actually neuroprotective in neonatal hypoxic–ischemic encephalopathy. We evaluated the effect of intracerebroventricular administration of nipradilol (3,4-dihydro-8-(2-hydroxy-3-isopropylamino)-propoxy-3-nitroxy-2H-1-benzopyran), a potent NO donor, at various concentrations (0.1 μM to 1 mM in 5 μl PBS/brain) to neonatal rats with hypoxic–ischemic treatment. The extent of the infarct area in the brain was significantly reduced by injection of the 1 μM nipradilol solution. However, denitro-nipradilol (3,4-dihydro-8-(2-hydroxy-3-isopropylamino)-propoxy-3-hydroxy-2H-1-benzopyran), that does not release NO, did not show the neuroprotective effect, suggesting that NO released from nipradilol exerts a neuroprotective effect on neonatal neurons.