The Blockade of NF-{kappa}B Activation by a Specific Inhibitory Peptide has a Strong Neuroprotective Role in a Sprague-Dawley Rat Kernicterus Model [Neurobiology]

October 23rd, 2015 by Li, M., Song, S., Li, S., Feng, J., Hua, Z.

Kernicterus, the permanent nerve damage occurs as a result of bilirubin precipitation, still occurs worldwide and may lead to death or permanent neurological impairments. However, the underlying mechanisms remain unclear and effective therapeutic strategies are lacking. The present study aims to investigate the activation of nuclear factor kappa B (NF-κB) and to identify the effect of NF-κB inhibition on the newborn rat Kernicterus model. The NF-κB essential modifier-binding domain peptide (NBD), coupled with the HIV trans-activator of transcription peptide (TAT) was used to inhibit NF-κB. NF-κB was significantly activated in the cerebrum at 1 and 3 h (P < 0.05) after the model was established, as measured by the electrophoretic mobility shift assay (EMSA). NF-κB activation was inhibited by intraperitoneal administration of TAT-NBD. The general conditions of the TAT-NBD-treated rats were improved, meanwhile, these rats performed much better on the neurological evaluation, the rotarod test and the Morris water maze test (P<0.05) than the vehicle-treated rats at 28 days. Furthermore, the morphology of the nerve cells was better preserved in the TAT-NBD group, and displayed less neurodegeneration and astrocytosis. Simultaneously, apoptosis in the brain was attenuated, and the levels of the TNF-α and IL-1β proteins were decreased (P < 0.01). These results suggested that NF-κB was activated and inhibition of NF-κB activation by TAT-NBD not only attenuates the acute neurotoxicity, apoptosis and inflammation, but also improved the long-term neurobehavioral impairments in the Kernicterus model rats in vivo. Thus, inhibiting NF-κB activation might be a potential therapeutic approach for Kernicterus.
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