Neuroprotective potential of the NF-κB inhibitor peptide IKK-NBD in cerebral ischemia-reperfusion injury.
2010
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 24 h post reperfusion following 1 h of ischemia after pre-treatment with either 40 μg 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.
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