BACKGROUND/AIMS: Ischemic stroke results in increased cerebral infarction, neurological deficits and neuroinflammation. The underlying mechanisms involving the anti-inflammatory and neuroprotective properties of α-Lipoic acid (α-LA) remain poorly understood. Herein, we investigated the potential role of α-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 TTC 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-κB were measured using western blot. In the in vitro study, the expressions of microglia M1/M2 phenotype were evaluated using qRT-PCR, and immunofluorescence staining was used to assess the nuclear translocation of NF-κB. RESULTS: Both 20 mg/kg and 40 mg/kg of α-LA alleviated infarct size, brain edema, and neurological deficits. Furthermore, α-LA induced the polarization of microglia to the M2 phenotype, modulated the expression of IL-1β, IL-6, TNF-α and IL-10, and attenuated the activation of NF-κB after MCAO. α-LA inhibited the expression of M1 markers, increased activation of the M2 markers, and suppressed the nuclear translocation of NF-κB in LPS-stimulated BV2 microglia. CONCLUSIONS: α-LA improved neurological outcome in experimental stroke via modulating microglia M1/M2 polarization. The potential mechanism of α-LA might be mediated by inhibition of NF-κB activation via regulating phosphorylation and nuclear translocation of p65.
BACKGROUND/AIMS: Ischemic stroke results in increased cerebral infarction, neurological deficits and neuroinflammation. The underlying mechanisms involving the anti-inflammatory and neuroprotective properties of α-Lipoic acid (α-LA) remain poorly understood. Herein, we investigated the potential role of α-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 TTC 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-κB were measured using western blot. In the in vitro study, the expressions of microglia M1/M2 phenotype were evaluated using qRT-PCR, and immunofluorescence staining was used to assess the nuclear translocation of NF-κB. RESULTS: Both 20 mg/kg and 40 mg/kg of α-LA alleviated infarct size, brain edema, and neurological deficits. Furthermore, α-LA induced the polarization of microglia to the M2 phenotype, modulated the expression of IL-1β, IL-6, TNF-α and IL-10, and attenuated the activation of NF-κB after MCAO. α-LA inhibited the expression of M1 markers, increased activation of the M2 markers, and suppressed the nuclear translocation of NF-κB in LPS-stimulated BV2 microglia. CONCLUSIONS: α-LA improved neurological outcome in experimental stroke via modulating microglia M1/M2 polarization. The potential mechanism of α-LA might be mediated by inhibition of NF-κB activation via regulating phosphorylation and nuclear translocation of p65.
Authors: Baruh Polis; Margherita Squillario; Vyacheslav Gurevich; Kolluru D Srikanth; Michael Assa; Abraham O Samson Journal: Neurochem Res Date: 2022-01-31 Impact factor: 3.996
Authors: Mona G Elhadidy; Ahlam Elmasry; Hassan Reda Hassan Elsayed; Mohammad El-Nablaway; Shereen Hamed; Mahmoud M Elalfy; Mohammed R Rabei Journal: Heliyon Date: 2021-10-13