Correlation Of NF-kappaB Signaling Pathway And Secondary Brain Injury After Intracerebral Hemmorhage

Objective and BackgroundIntracerebral hemmorhage (ICH) is an acute cerebrovascular disease with high morbidity and mortality.Hemorrhagic brain injury in the past was mainly due to bleeding mechanical injury and compression of hematoma, recent results show, the secondary brain injury induced by perihematomal zone may be more important. Hemorrhagic brain injury includes not only the hematoma mass effect and directly damage to the surrounding tissue, but also the surrounding tissue edema, ischemia, inflammation, cell toxicity and other reasons.NF-icB (nuclear factor-icappaB) is a multi-directional transcriptional regulatory protein, when it activated, can enter the nucleus and bind with DNA,. This results in the transcriptional induction of genes for manyproinflammatory substances, such as TNF-α, IL-2,3,6 and IL-8,transforming growth factor, ICAM-1, the iNOS, epoxide enzyme-2 and so on. Its activation has been played a key role in the inflammatory response in the cerebral diseases. Domestic and international studies have demonstrated that chronic inflammation, cerebral ischemia and apoptosis are closely related to the activation of NF-κB.We investigated the levels of NF-κB and inhibition of factor IκBs after ICH to discuss the possible mechanism of NF-κB signaling pathway in secondary brain injury after ICH. Materials and methodsThis study was understaken to investigate the expression of NF-κB and inhibition of factor IκBs in ICH model and to clarify the relationship of NF-κB signaling pathway in secondary brain injury. A total of 100 rats were randomly divided into 7 groups:control group; 2 hours,6 hours,12 hours,1 day,3 days and 7 days groups. The animals in control groups were subjected to physiological saline injection into ipsilateral basal ganglia (IBG), and the other animals were subjected to autologous blood injection into IBG and were killed 2 hours,6 hours,12 hours,1 day,3 days and 7 days after ICH. Brain water content of IBG, contralateral basal ganglia (CBG) and cerebellum (C) was measured and the NF-κB P65 and IκBα. expression was assessed by Immunohistochemistry and Western blot (WB)ResultsThe brain water content of IBG was found to be 78.702±0.065% at 2h, 79.305±0.139% at 6h,80.425±0.409% at 12h,81.355±0.425% on Id,82.598±0.311% on 3d, and 80.625±0.512% on 7d, respectively, which reached to the peak point on 3d. NF-κB and IκBs Immunoreactivities were very low in the cerebral hemispheres of the control rat.However,NF-KB and IκBs protein levels were increased markedly in the first 2 hours after ICH, peaked at day 1, and were still detcetable at day 7 after ICH.NF-κB and IκBs Positive cells were found in the Perihematomal zone. Correlation analysis revealed that NF-κB signaling pathway is strongly positvely correlated with the development of econdary brain injury in a rat ICH model.ConclusionsThe high expression of NF-κB and IκBs may participate in secondary brain injury after intracerebral hemorrhage...