Neuroprotection by a novel compound, NS521

NS521 (1-(1-butyl)-4-(2-oxo-1-benzimidazolinyl)piperidine) belongs to a gro up of novel benzimidazolones, which exhibit neurotrophic-like activities. I n vitro, NS521 rescued neuronal PC12 cells from death induced by serum and nerve growth factor deprivation. The survival effect of NS521 appeared to r eflect a delay of the apoptotic process, because the extent of DNA fragment ation was attenuated transiently by NS521. NS521 did not preserve the neuri tes of the rescued cells, which, otherwise, appeared to be healthy and were able to regenerate when serum and nerve growth factor were added back to t he culture. In vivo, NS521 provided significant protection against the dela yed loss of hippocampal CA, neurons in a gerbil model of transient global i schemia. A neuroprotective effect of NS521 in the peripheral nervous system also was observed in rats after transection of the sciatic nerve, where da ily treatment with NS521 was found to inhibit retrograde degeneration of th e transected nerve. The neuroprotective effect of NS521 is unlikely to be m ediated through neurotrophin receptors, such as TrkA, because NS521 did not induce phosphorylation of the 44-and 42-kDa isoforms of mitogen-activated protein kinases (ERK1/2) in PC12 cells.