Formyl Peptide Receptor 1 Signaling in Acute Inflammation and Neural Differentiation Induced by Traumatic Brain Injury.
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ABSTRACT:
SUBMITTER: Fusco R
PROVIDER: S-EPMC7563302 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
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Formyl Peptide Receptor 1 Signaling in Acute Inflammation and Neural Differentiation Induced by Traumatic Brain Injury.
Fusco Roberta R Gugliandolo Enrico E Siracusa Rosalba R Scuto Maria M Cordaro Marika M D'Amico Ramona R Evangelista Maurizio M Peli Angelo A Peritore Alessio Filippo AF Impellizzeri Daniela D Crupi Rosalia R Cuzzocrea Salvatore S Di Paola Rosanna R
Biology 20200820 9
Traumatic brain injury (TBI) is a shocking disease frequently followed by behavioral disabilities, including risk of cerebral atrophy and dementia. N-formylpeptide receptor 1 (FPR1) is expressed in cells and neurons in the central nervous system. It is involved in inflammatory processes and during the differentiation process in the neural stem cells. We investigate the effect of the absence of Fpr1 gene expression in mice subjected to TBI from the early stage of acute inflammation to neurogenesi ...[more]
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Project description:BackgroundAucubin (Au), an iridoid glycoside from natural plants, has antioxidative and anti-inflammatory bioactivities; however, its effects on a traumatic brain injury (TBI) model remain unknown. We explored the potential role of Au in an H2O2-induced oxidant damage in primary cortical neurons and weight-drop induced-TBI in a mouse model.MethodsIn vitro experiments, the various concentrations of Au (50 μg/ml, 100 μg/ml, or 200 μg/ml) were added in culture medium at 0 h and 6 h after neurons stimulated by H2O2 (100 μM). After exposed for 12 h, neurons were collected for western blot (WB), immunofluorescence, and M29,79-dichlorodihydrofluorescein diacetate (DCFH-DA) staining. In vivo experiments, Au (20 mg/kg or 40 mg/kg) was administrated intraperitoneally at 30 min, 12 h, 24 h, and 48 h after modeling. Brain water content, neurological deficits, and cognitive functions were measured at specific time, respectively. Cortical tissue around focal trauma was collected for WB, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, Nissl staining, quantitative real time polymerase chain reaction (q-PCR), immunofluorescence/immunohistochemistry, and enzyme linked immunosorbent assay (ELISA) at 72 h after TBI. RNA interference experiments were performed to determine the effects of nuclear factor erythroid-2 related factor 2 (Nrf2) on TBI mice with Au (40 mg/kg) treatment. Mice were intracerebroventricularly administrated with lentivirus at 72 h before TBI establishment. The cortex was obtained at 72 h after TBI and used for WB and q-PCR.ResultsAu enhanced the translocation of Nrf2 into the nucleus, activated antioxidant enzymes, suppressed excessive generation of reactive oxygen species (ROS), and reduced cell apoptosis both in vitro and vivo experiments. In the mice model of TBI, Au markedly attenuated brain edema, histological damages, and improved neurological and cognitive deficits. Au significantly suppressed high mobility group box 1 (HMGB1)-mediated aseptic inflammation. Nrf2 knockdown in TBI mice blunted the antioxidant and anti-inflammatory neuroprotective effects of the Au.ConclusionsTaken together, our data suggest that Au provides a neuroprotective effect in TBI mice model by inhibiting oxidative stress and inflammatory responses; the mechanisms involve triggering Nrf2-induced antioxidant system.
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