Effects Of NF-κB On Neuronal Cell Plasmolemma Permeability And Neurological Dysfunction In Mice After Traumatic Brain Injury

Objective: To investigate the effects and the mechanism of nuclear factor kappa B (NF-κB) by administration of SN50, a specific NF-κB inhibitor, on traumatic brain injury (TBI)-induced neuronal cell plasmolemma permeability and dysfunction in mice TBI model.Methods: TBI model was established by weight drop device in adult mice based on procedures previously reported. Two hundreds mature male mice were randomly divided into normal saline (1μl)-treated control group and SN50 - (0.1μg/1μl) treated group for time course works of TBI. Fifty were used to assess the number of cell death by nuclear staining with Propidium Iodine (PI) for 1 h, 6 h, 12 h, 24 h, and 48 h. Mice post-TBI were pretreatment with intraperitoneal injection of PI (0.4mg/ml) 1 h before sacrificed. Other animals were sacrificed at 1 h, 6 h, 12 h, 24 h, and 48 h time point after suffering TBI. The brain tissues were undergone immunohistochemical or Western blot analyses for Caspase-3 activity, tbid, TNF-α, Nestin, lysosomal enzyme Cathepsin B. Brain tissue defect was assessed by Lesion Volume Test. Neurological function was detected by Motor Test and Morris Water Maze. SN50 - and saline -treated mice subjected to TBI were also compared with each other respect to neurological function.Results: Lateral cerebral ventricle administration of SN50 before TBI in mice resulted in improved neurological function when compared with saline given mice control groups, as assessed by Immunohistochemical staining method and Behavior test after TBI. Caspase-3 activity, tbid, TNF-α, lysosomal enzyme Cathepsin B, Caspase-1 quantified by immunoblotting, was considerably increased in saline control mice that underwent TBI, and this increase was significantly diminished in SN50-treated mice. The quantity analysis of Nestin showed that TBI-induced activation of Nestin remarkably enhanced by SN50 treatment. Conclusion: 1. Lateral cerebral ventricle administration of specific NF-κB inhibitor SN50 (0.1μg/1μl) could significantly insult neuronal cell plasmolemma permeability and attenuated the TBI-induced neuronal cell death and dysfunction. 2. The effect of NF-κB on TBI induced neuronal cell plasmolemma permeability and neuronal dysfunction may due to the regulatory mechanism through several cell death pathways.