Final solution contained RNAse free water, 0.08 mM DOPE, 0.24% chloroform/7% EtOH, glucose 12.5%, and 0.04 mM JetSI. For intracerebral siRNA administration, 0.4 μg siRNA/mice were administered (volume of injection=2 μl) 24 h before ibotenate. SiRNA sequences and primers for PCR were reported previously.

Brain protection of the newborn remains a challenging priority and represents a totally unmet medical need. Pharmacological inhibition of caspases appears as a promising strategy for neuroprotection. In a translational perspective, we have developed a pentapeptide-based group II caspase inhibitor, TRP601/ORPHA133563, which reaches the brain, and inhibits caspases activation, mitochondrial release of cytochrome c, and apoptosis in vivo. Single administration of TRP601 protects newborn rodent brain against excitotoxicity, hypoxia-ischemia, and perinatal arterial stroke with a 6-h therapeutic time window, and has no adverse effects on physiological parameters. Safety pharmacology investigations, and toxicology studies in rodent and canine neonates, suggest that TRP601 is a lead compound for further drug development to treat ischemic brain damage in human newborns.