| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2006444 | Peptides | 2011 | 7 Pages |
In the present study, the newly synthesized TRH analog (l-pGlu-(2-propyl)-l-His-l-ProNH2; NP-647) was evaluated for its effects in in vitro (oxygen glucose deprivation (OGD)-, glutamate- and H2O2-induced injury in PC-12 cells) and in vivo (transient global ischemia) models of cerebral ischemic injury. PC-12 cells were subjected to oxygen and glucose deprivation for 6 h. Exposure of NP-647 was given before and during OGD. In glutamate and H2O2 induced injury, exposure of NP-647 was given 1, 6 and 24 h prior to exposure of glutamate and H2O2 exposure. NP-647, per se found to be non-toxic in 1–100 μM concentrations. NP-647 showed protection against OGD at the 1 and 10 μM. The concentration-dependent protection was observed in H2O2- and glutamate-induced cellular injury. In in vivo studies, NP-647 treatment showed protection of hippocampal (CA1) neuronal damage in transient global ischemia in mice and subsequent improvement in memory retention was observed using passive avoidance retention test. Moreover, administration of NP-647 resulted in decrease in inflammatory cytokines TNF-α and IL-6 as well as lipid peroxidation. These results suggest potential of NP-647 in the treatment of cerebral ischemia and its neuroprotective effect may be attributed to reduction of excitotoxicity, oxidative stress and inflammation.
► In this study, we have investigated neuroprotective potential of TRH analog NP-647 in cerebral ischemia models. ► NP-647 showed protection against oxygen deprivation, hydrogen peroxide and glutamate-induced cellular injury in PC-12 cells. ► NP-647 protected hippocampal CA1 neuron and improved memory retention in mice subjected to transient global ischemia. ► NP-647 treatment significantly decreased inflammatory cytokines TNF-α and IL-6 as well as lipid peroxidation in ischemic animals. ► Protective effect of NP-647 in cerebral ischemia was attributed to reduction of excitotoxicity, inflammation and oxidative stress.
