Targeting Oxidative Stress with Antioxidant Duotherapy after Experimental Traumatic Brain Injury
We assessed the effect of antioxidant therapy using the Food and Drug Administration-approved respiratory drug <i>N</i>-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-per...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/19/10555 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Jenni Kyyriäinen |
| collection | DOAJ |
| description | We assessed the effect of antioxidant therapy using the Food and Drug Administration-approved respiratory drug <i>N</i>-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% (<i>p</i> < 0.001) and neuroinflammation to –29% (<i>p</i> < 0.001) compared with untreated culture. The treatment also improved neuronal viability up to 72% of that in a positive control (<i>p</i> < 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 (<i>p</i> < 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. |
| first_indexed | 2024-03-10T07:00:10Z |
| format | Article |
| id | doaj.art-b998370c5ed947969d9f9c88922b1f47 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T07:00:10Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b998370c5ed947969d9f9c88922b1f472023-11-22T16:11:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-0122191055510.3390/ijms221910555Targeting Oxidative Stress with Antioxidant Duotherapy after Experimental Traumatic Brain InjuryJenni Kyyriäinen0Natallie Kajevu1Ivette Bañuelos2Leonardo Lara3Anssi Lipponen4Silvia Balosso5Elina Hämäläinen6Shalini Das Gupta7Noora Puhakka8Teemu Natunen9Teresa Ravizza10Annamaria Vezzani11Mikko Hiltunen12Asla Pitkänen13A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, FI-70211 Kuopio, FinlandA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, FI-70211 Kuopio, FinlandA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, FI-70211 Kuopio, FinlandA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, FI-70211 Kuopio, FinlandA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, FI-70211 Kuopio, FinlandDepartment of Neuroscience, Mario Negri Institute for Pharmacological Research IRCCS, 20156 Milano, ItalyA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, FI-70211 Kuopio, FinlandA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, FI-70211 Kuopio, FinlandA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, FI-70211 Kuopio, FinlandInstitute of Biomedicine, University of Eastern Finland, FI-70211 Kuopio, FinlandDepartment of Neuroscience, Mario Negri Institute for Pharmacological Research IRCCS, 20156 Milano, ItalyDepartment of Neuroscience, Mario Negri Institute for Pharmacological Research IRCCS, 20156 Milano, ItalyInstitute of Biomedicine, University of Eastern Finland, FI-70211 Kuopio, FinlandA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, FI-70211 Kuopio, FinlandWe assessed the effect of antioxidant therapy using the Food and Drug Administration-approved respiratory drug <i>N</i>-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% (<i>p</i> < 0.001) and neuroinflammation to –29% (<i>p</i> < 0.001) compared with untreated culture. The treatment also improved neuronal viability up to 72% of that in a positive control (<i>p</i> < 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 (<i>p</i> < 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.https://www.mdpi.com/1422-0067/22/19/10555antioxidant treatmentcytokinelateral fluid-percussion injury<i>N</i>-acetylcysteineoxidative stresssulforaphane |
| spellingShingle | 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 Targeting Oxidative Stress with Antioxidant Duotherapy after Experimental Traumatic Brain Injury International Journal of Molecular Sciences antioxidant treatment cytokine lateral fluid-percussion injury <i>N</i>-acetylcysteine oxidative stress sulforaphane |
| title | Targeting Oxidative Stress with Antioxidant Duotherapy after Experimental Traumatic Brain Injury |
| title_full | Targeting Oxidative Stress with Antioxidant Duotherapy after Experimental Traumatic Brain Injury |
| title_fullStr | Targeting Oxidative Stress with Antioxidant Duotherapy after Experimental Traumatic Brain Injury |
| title_full_unstemmed | Targeting Oxidative Stress with Antioxidant Duotherapy after Experimental Traumatic Brain Injury |
| title_short | Targeting Oxidative Stress with Antioxidant Duotherapy after Experimental Traumatic Brain Injury |
| title_sort | targeting oxidative stress with antioxidant duotherapy after experimental traumatic brain injury |
| topic | antioxidant treatment cytokine lateral fluid-percussion injury <i>N</i>-acetylcysteine oxidative stress sulforaphane |
| url | https://www.mdpi.com/1422-0067/22/19/10555 |
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