Abstract
Intracerebral hemorrhage (ICH) is a devastating disease with high rates of mortality and morbidity. The aim of this study was to explore whether Sodium Benzoate (NaB) could reduce neural cell apoptosis and alleviate neurological deficits after ICH. To assess the therapeutic effects of NaB, first, we measured brain water content, neurobehavior, and blood-brain barrier (BBB) integrity at 24 h after ICH in different groups. Then western blot and immunofluorescence staining (IF) were applied to test the levels of different proteins. Transmission electron microscope (TEM) was used to observe ultra-structures within the cells in different groups. The results showed that levels of DJ-1, p-Akt and p-IκB kinase (IKK) increased after ICH and peaked at 24 h. Besides, NaB significantly upregulated DJ-1 in both cytoplasm and mitochondria, and also increased the levels of p-Akt, p-IKK and Bcl-2/Bax ratio, but decreased the levels of caspase-3 and caspase-9. Additionally, NaB decreased reactive oxygen species (ROS) while increased adenosine triphosphate (ATP), which then improving the neurological functions at 24 h and long-term (21 days) memory and spatial learning ability after ICH. However, the results mentioned above could be greatly reversed by MK2206 and rotenone. Therefore, we concluded that NaB could attenuate secondary brain injury via inhibiting neuronal apoptosis and reducing mitochondria-mediated oxidative stress via DJ-1/Akt/IKK/NFκB pathway.
Highlights
Intracerebral hemorrhage (ICH), one of the most common types of stroke, is still a serious concern for public health (Feigin et al, 2009)
IF staining suggested that DJ-1 was colocalized with neuron, microglia and astrocytes and the level of DJ-1 was dramatically upregulated after ICH (Figure 2D)
We explored the neuroprotective effects of sodium benzoate (NaB) through a new mechanism mediated by DJ-1/Akt/inhibitor of nuclear factor kappa-B kinase (IKK)/ NFκB pathway in the experimental ICH in rats
Summary
Intracerebral hemorrhage (ICH), one of the most common types of stroke, is still a serious concern for public health (Feigin et al, 2009). It owns a high rate of disability and death, causing a substantial burden on both patients and their families (van Asch et al, 2010; Krishnamurthi et al, 2014). DJ-1, a homo-dimeric protein, is characterized by multiple biological activities It was originally identified as an oncogene, and its mutations cause a familial type of Parkinson’s diseasePARK7 (Lill, 2016). We proposed that NaB could exert its neuroprotective effects in experimental ICH by regulating the expression of DJ-1
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