The neuronal nitric oxide synthase inhibitor, TRIM, as a neuroprotective agent: effects in models of cerebral ischaemia using histological and magnetic resonance imaging techniques.

摘要: Most neuroprotective compounds that appear promising in the pre-clinical phase of testing are subsequently dismissed as relatively ineffective when entered into large-scale clinical trials. Many studies potential candidates evaluate efficacy only one or possibly two different models ischaemia. In this study we examined effects 1,2-trifluoromethylphenyl imidazole (TRIM), a novel neuronal nitric oxide synthase (nNOS) inhibitor, three cerebral ischaemia (global gerbil, global rat and focal rat). addition, to follow progression pathology, also compared traditional histology methods with more advanced magnetic resonance imaging (MRI) endpoint measures for neurological damage neuroprotection. TRIM (50 mg/kg i.p.) prevented ischaemia-induced hippocampal following gerbils administered before immediately post-occlusion, but failed protect administration was delayed until 30 min post-occlusion. Further indicated compound (administered at 50 mg/kg, i.p., after occlusion) protected four-vessel occlusion (4-VO) model using both histological diffusion-weighted (DW) techniques. final study, i.p. provided significant reduction infarct volume 4 24 h measured proton density (PD)-weighted (MRI). This confirmed These confirm nNOS inhibitors may have utility stroke provide evidence combined can powerful method assessing rodent