The Role of Alpha-Lipoic Acid in the Pathomechanism of Acute Ischemic Stroke

Background/Aims: Ischemic stroke results in increased cerebral infarction, neurological deficits and neuroinflammation. The underlying mechanisms involving the anti-inflammatory and neuroprotective properties of alpha-Lipoic acid (alpha-LA) remain poorly understood. Herein, we investigated the potential role of alpha-LA in a middle cerebral artery occlusion (MCAO) rat model and an in vitro lipopolysaccharide (LPS)-induced microglia inflammation model. Methods: In the in vivo study, infarct volume was examined by TT[staining and Garcia score was used to evaluate neurologic recovery. The cytokines were evaluated by enzyme-linked immunosorbent assay, and protein expression of microglia phenotype and NF-kappa B were measured using western blot. In the in vitro study, the expressions of microglia M1/M2 phenotype were evaluated using ciRT-PCR, and immunofluorescence staining was used to assess the nuclear translocation of NF-kappa B. Results: Both 20 mg/kg and 40 mg/kg of alpha-LA alleviated infarct size, brain edema, and neurological deficits. Furthermore, alpha-LA induced the polarization of microglia to the M2 phenotype, modulated the expression of IL-113, IL-6, TNF-alpha and IL-10, and attenuated the activation of NE-kappa B after MCAO. alpha-LA inhibited the expression of M1 markers, increased activation of the M2 markers, and suppressed the nuclear translocation of NF-kappa B in LPS-stimulated BV2 microglia. Conclusions: alpha-LA improved neurological outcome in experimental stroke via modulating microglia M1/M2 polarization. The potential mechanism of alpha-LA might be mediated by inhibition of NE-kappa B activation via regulating phosphorylation and nuclear translocation of p65. (C) 2018 The Author(s) Published by S. Karger AG, Basel.