Overexpressed HspB6 Underlines a Novel Inhibitory Role in Kainic Acid-Induced Epileptic Seizure in Rats by Activating the cAMP-PKA Pathway.

Epilepsy is a commonly occurring neurological disease that has a large impact on the patient's daily life. Phosphorylation of heat shock protein B6 (HspB6) has been reported to protect the central nervous system. In this investigation, we explored whether HspB6 played a positive effect on epilepsy with the involvement of the cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) pathway. The epileptic seizure was induced in rats by intraperitoneal injection of kainic acid (KA). The extent of HspB6 phosphorylation and expressions of HspB6, PKA, and inflammatory factors TNF-α, IL-1ß, and IL-6 were quantified along with neuronal apoptosis. To further understand the regulatory mechanism of the HspB6 in the hippocampus, we altered the expression and the extent of HspB6 phosphorylation to see whether the cAMP-PKA pathway was inactivated or not in hippocampal neurons of rats post KA. Results showed that HspB6 was poorly expressed, resulting in the inactivation of the cAMP-PKA pathway in rats post KA, as well as an aggravated inflammatory response and hippocampal neuronal apoptosis. HspB6 overexpression and the cAMP-PKA pathway activation decreased the expression of inflammatory factors and inhibited hippocampal neuronal apoptosis. Additionally, HspB6 phosphorylation further augments the inhibitory effects of HspB6 on the inflammatory response and hippocampal neuronal apoptosis. The cAMP-PKA pathway activation was found to result in increased HspB6 phosphorylation. HspB6 decreased apoptosis signal-regulating kinase 1 (ASK1) expression to inhibit inflammatory response and hippocampal neuronal apoptosis. Collectively, our findings demonstrate that activation of the cAMP-PKA pathway induces overexpression and partial phosphorylation of HspB6 lead to the inhibition of ASK1 expression. This in turn protects rats against epilepsy and provides a potential approach to prevent the onset of epileptic seizure in a clinical setting.

Thioredoxin is a novel diagnostic and prognostic marker in patients with ischemic stroke.

Serum thioredoxin (TRX), a redox-regulating protein with antioxidant activity, was recognized as an oxidative-stress marker. The purpose of this study was to investigate the potential diagnostic and prognostic role of TRX in Chinese patients with acute ischemic stroke (AIS). From January 1, 2012, to December 31, 2013, all patients with first-ever acute ischemic stroke were recruited to participate in the study. Serum levels of TRX were assayed with solid-phase sandwich ELISA, and severity of stroke was evaluated with the National Institutes of Health Stroke Scale (NIHSS) score on admission. Short-term functional outcome was measured by a modified Rankin scale (mRS) 3 months after admission. Multivariate analyses were performed using logistic regression models. We found the serum TRX reflected the disease severity of AIS. There was a significant positive association between serum TRX levels and NIHSS scores (r= 0.476, P<0.0001). Based on the ROC curve, the optimal cutoff value of serum TRX levels as an indicator for auxiliary diagnosis of AIS was projected to be 11.0 ng/ml, which yielded a sensitivity of 80.3% and a specificity of 73.7%, with the area under the curve at 0.807 (95% CI, 0.766-0.847). Elevated TRX (≥ 20.0 ng/ml) was an independent prognostic marker of short-term functional outcome [odds ratio (OR) 9.482 (95% CI, 3.11-8.15) P<0.0001; adjusted for NIHSS, other predictors and vascular risk factors] in patients with AIS. TRX improved the area under the receiver operating characteristic curve of the NHISS score for functional outcome from 0.722 (95% CI, 0.662-0.782) to 0.905 (95% CI, 0.828-0.962; P<0.0001). Our study demonstrated that elevated serum TRX level at admission was a novel diagnostic and prognostic marker in patients with acute ischemic stroke.