Neuroprotective effect of nipradilot, 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 mu M to 1 mM in 5 mu l 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 mu M nipradilol solution. However, denitro-nipradilol (3,4-dihydro-8-(2-hydroxy-3-isopropytamino)-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. (c) 2006 Elsevier Ireland Ltd. All rights reserved.