title: Neuroprotective potential of the NF-κB inhibitor peptide IKK-NBD in cerebral ischemia-reperfusion injury.
abstract: Inflammation plays an important role in ischemic pathology. NF-κB is a transcription factor that has a crucial role in inflammation and cell survival, but its precise role in the ischemic aftermath is still uncertain. Therefore, we evaluated the effect of intracerebroventricular administration of a highly specific NF-κB inhibitor peptide, IKK-NBD, on transient focal cerebral ischemic injury in rat using middle cerebral artery occlusion model. The assessment of ischemia-induced neurological deficits, alterations in the proinflammatory cytokine IL-1β level, OX-42 immunoreactivity, changes in blood-brain barrier (BBB) permeability, reactive oxygen species (ROS) production and DNA fragmentation by terminal dUTP nick end labelling (TUNEL) were monitored at 24h post reperfusion following 1h of ischemia after pre-treatment with either 40μg of IKK-NBD or the inactive IKK-NBD peptide, which served as control. Pre-treatment with IKK-NBD peptide significantly ameliorated the cerebral ischemia-induced neurological deficits. Quantification of IL-1β by ELISA revealed significantly reduced striatal IL-1β level in IKK-NBD peptide treated rats. The treatment also resulted in reduced staining of microglial OX-42 and significantly reduced extravasation of Evans blue dye, indicating protection of BBB from ischemic insult. These results indicate that specific NF-κB inhibition downplays post-ischemic inflammation. Furthermore, reduction in DNA fragmentation as assessed by TUNEL staining also confirms the neuroprotective effect of IKK-NBD peptide. Thus, it may be inferred that IKK-NBD peptide reduces ischemic brain damage and this can, at least partly, be attributed to reduction in inflammation following ischemic injury.
authors.affiliation: Division of Pharmacology, Central Drug Research Institute (CSIR), M.G. Marg, Lucknow 226001, India.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Desai
authors.forename: Nilendra
authors.initials: N
authors.lastname: Singh
authors.forename: Ram
authors.initials: R
authors.lastname: Raghubir
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000502:physiology* / Q000627:therapeutic use; D016923:Cell Death / Q000502:physiology; D051550:I-kappa B Kinase / Q000502:physiology* / Q000627:therapeutic use; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D018836:Inflammation Mediators / Q000502:physiology* / Q000627:therapeutic use; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000502:physiology* / Q000627:therapeutic use; D010455:Peptides / Q000502:physiology* / Q000627:therapeutic use; D016601:RNA-Binding Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
chemical_list: D002352:Carrier Proteins; C491967:Elp1 protein, rat; D018836:Inflammation Mediators; D016328:NF-kappa B; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D010455:Peptides; D016601:RNA-Binding Proteins; D051550:I-kappa B Kinase