Neurochemistry International vol 57 (8), 10, 876-883 Neuroprotective potential of the NF-țB inhibitor peptide IKK-NBD in cerebral ischemia-reperfusion injury Abhishek Desai, Nilendra Singh and Ram Raghubir* Division of Pharmacology, Central Drug Research Institute, Lucknow, India. Abstract Inflammation plays an important role in ischemic pathology. NF-țB 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-țB inhibitor peptide, IKK-NBD, on transient focal cerebral ischemic injury. Assessment of ischemia-induced neurological deficit and inflammatory mediators such as IL-1ȕ 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-1ȕ by ELISA revealed significantly reduced striatal IL-1ȕ 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-țB 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. Keywords : cerebral ischemia, reperfusion injury, IKK-NBD, Neuroprotective, NF-țB Cerebral ischemia is a pathological disorder caused due to interruption in blood supply to the brain that is usually the result of formation of a clot or lodging of an embolus in a blood vessel in the brain. The consequent lack of glucose and oxygen, if prolonged, leads to permanent damage to the nervous tissue. Apart from mortality, such damage is reflected in severe debilities that often are not reversed completely. Apart from recombinant tissue plasminogen activator, the only FDA approved drug for treatment of ischemia that dissolves the blood clot to initiate reperfusion, no other drug has proved effective in curing ischemia. Nuclear factor kappa B (NF-țB) is a transcription factor that modulates diverse physiological and pathological phenomena. This protein is formed by the homo- or heterodimerization of p65, p50, p52, c-rel and relB. It is sequestered in the cytoplasm by inhibitor of kappa B (IțB) proteins. Upon activation of the NF- țB pathway, the Iț%Į is phosphorylated at specific serine residues, leading to its ubiquitination and proteasomal degradation. The NF-țB dimer then translocates to the nucleus, where it binds to țB promoter sequences and initiates transcription.