Inhibition of neuronal nitric oxide synthase-mediated activation of poly(ADP-ribose) polymerase in traumatic brain injury: neuroprotection by 3-aminobenzamide.

摘要: Abstract Focal traumatic injury to the cerebral cortex is associated with early activation of neuronal isoform nitric oxide synthase (nNOS), where high concentrations oxide-derived free radicals elicit extensive DNA damage. Subsequent nuclear repair enzyme poly(ADP-ribose) polymerase (PARP) causes a severe energy deficit leading ultimate demise affected neurons. Little known about temporal relationship nNOS and PARP neuroprotective efficacy their selective blockade in brain injury. To determine activation, was induced by cryogenic lesion somatosensory applying pre-cooled cylinder after trephination for 6 s intact dura mater. Pre-treatment 3-bromo-7-nitroindazole (BrNI; 25 mg/kg, i.p.), pre- or combined post-treatment 3-aminobenzamide (AB; 10 mg/kg (i.c.v.) 10 mg/kg/h (i.p.)) were used inhibit PARP, respectively. Cold lesion-induced changes neuroprotection BrNI AB determined using immunocytochemistry immunodot-blot detection poly(ADP-ribose; PAR), end-product triphenyltetrazolium-chloride assay assess volume. PAR immunoreactivity reached its peak 30 min post-lesion followed gradual reduction immunolabeling. pre-treatment significantly decreased concentration damaged cortex. i.c.v. infusion markedly diminished cortical reduced volume 24 h post-injury. In contrast, i.p. treatment remained largely ineffective. conclusion, our data indicate cold that is, at least part, related induction supports relevance and/or inhibition therapeutic approaches