Neuroprotective potential of the NF-κB inhibitor peptide IKK-NBD in cerebral ischemia-reperfusion injury

Inflammation plays an important role in ischemic pathology NF-kappa B 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-kappa B 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-1 beta 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 24 h post reperfusion following 1 h of ischemia after pretreatment with either 40 mu g 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-1 beta by ELISA revealed significantly reduced striatal IL-1 beta 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-kappa B 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 (C) 2010 Elsevier Ltd All rights reserved