Targeting Oxidative Stress with Antioxidant Duotherapy after Experimental Traumatic Brain Injury
| Autor: | Jenni, Kyyriäinen, Natallie, Kajevu, Ivette, Bañuelos, Leonardo, Lara, Anssi, Lipponen, Silvia, Balosso, Elina, Hämäläinen, Shalini, Das Gupta, Noora, Puhakka, Teemu, Natunen, Teresa, Ravizza, Annamaria, Vezzani, Mikko, Hiltunen, Asla, Pitkänen |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Cell Survival NF-E2-Related Factor 2 QH301-705.5 Gene Expression sulforaphane Antioxidants Article Cell Line Rats Sprague-Dawley Isothiocyanates Brain Injuries Traumatic cytokine Animals lateral fluid-percussion injury oxidative stress Biology (General) QD1-999 Cells Cultured Neurons Brain antioxidant treatment N-acetylcysteine Acetylcysteine Mice Inbred C57BL Disease Models Animal Chemistry Sulfoxides Microglia Heme Oxygenase-1 |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 10555, p 10555 (2021) International Journal of Molecular Sciences Volume 22 Issue 19 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | We assessed the effect of antioxidant therapy using the Food and Drug Administration-approved respiratory drug N-acetylcysteine (NAC) or sulforaphane (SFN) as monotherapies or duotherapy in vitro in neuron-BV2 microglial co-cultures and validated the results in a lateral fluid-percussion model of TBI in rats. As in vitro measures, we assessed neuronal viability by microtubule-associated-protein 2 immunostaining, neuroinflammation by monitoring tumor necrosis factor (TNF) levels, and neurotoxicity by measuring nitrite levels. In vitro, duotherapy with NAC and SFN reduced nitrite levels to 40% (p < 0.001) and neuroinflammation to –29% (p < 0.001) compared with untreated culture. The treatment also improved neuronal viability up to 72% of that in a positive control (p < 0.001). The effect of NAC was negligible, however, compared with SFN. In vivo, antioxidant duotherapy slightly improved performance in the beam walking test. Interestingly, duotherapy treatment decreased the plasma interleukin-6 and TNF levels in sham-operated controls (p < 0.05). After TBI, no treatment effect on HMGB1 or plasma cytokine levels was detected. Also, no treatment effects on the composite neuroscore or cortical lesion area were detected. The robust favorable effect of duotherapy on neuroprotection, neuroinflammation, and oxidative stress in neuron-BV2 microglial co-cultures translated to modest favorable in vivo effects in a severe TBI model. |
| Databáze: | OpenAIRE |
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