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 intra-cerebroventricular administration of a highly specific NF-κB inhibitor peptide, IKK-NBD, on transient focal cerebral ischemic injury. Assessment of ischemia-induced neurological deficit and inflammatory mediators such as IL-1β quantification, 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 after pre-treatment with either 40 µg of IKK-NBD or the inactive IKK-NBD peptide as control.
Pre-treatment with IKK-NBD significantly ameliorated the cerebral ischemia-induced neurological deficits. Quantification of IL-1β by ELISA revealed significantly reduced striatal IL-1β level in IKK-NBD treated rats. The treatment also resulted in reduced staining of microglial ox-42 and significantly reduced extravasation of Evans blue dye, indicating protection from ischemic blood brain barrier damage. 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 protective 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.
