Sulforaphane Ameliorates Metabolic Changes Associated With Status Epilepticus in Immature Rats
Status epilepticus (SE) is a common paediatric emergency with the highest incidence in the neonatal period and is a well-known epileptogenic insult. As previously established in various experimental and human studies, SE induces long-term alterations to brain metabolism, alterations that directly co...
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2022.855161/full |
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| author | Jan Daněk Šárka Danačíková David Kala Jan Svoboda Jan Svoboda Sonam Kapoor Antonín Pošusta Jaroslava Folbergrová Kateřina Tauchmannová Tomáš Mráček Jakub Otáhal Jakub Otáhal |
| author_facet | Jan Daněk Šárka Danačíková David Kala Jan Svoboda Jan Svoboda Sonam Kapoor Antonín Pošusta Jaroslava Folbergrová Kateřina Tauchmannová Tomáš Mráček Jakub Otáhal Jakub Otáhal |
| author_sort | Jan Daněk |
| collection | DOAJ |
| description | Status epilepticus (SE) is a common paediatric emergency with the highest incidence in the neonatal period and is a well-known epileptogenic insult. As previously established in various experimental and human studies, SE induces long-term alterations to brain metabolism, alterations that directly contribute to the development of epilepsy. To influence these changes, organic isothiocyanate compound sulforaphane (SFN) has been used in the present study for its known effect of enhancing antioxidative, cytoprotective, and metabolic cellular properties via the Nrf2 pathway. We have explored the effect of SFN in a model of acquired epilepsy induced by Li-Cl pilocarpine in immature rats (12 days old). Energy metabolites PCr, ATP, glucose, glycogen, and lactate were determined by enzymatic fluorimetric methods during the acute phase of SE. Protein expression was evaluated by Western blot (WB) analysis. Neuronal death was scored on the FluoroJadeB stained brain sections harvested 24 h after SE. To assess the effect of SFN on glucose metabolism we have performed a series of 18F-DG μCT/PET recordings 1 h, 1 day, and 3 weeks after the induction of SE. Responses of cerebral blood flow (CBF) to electrical stimulation and their influence by SFN were evaluated by laser Doppler flowmetry (LDF). We have demonstrated that the Nrf2 pathway is upregulated in the CNS of immature rats after SFN treatment. In the animals that had undergone SE, SFN was responsible for lowering glucose uptake in most regions 1 h after the induction of SE. Moreover, SFN partially reversed hypometabolism observed after 24 h and achieved full reversal at approximately 3 weeks after SE. Since no difference in cell death was observed in SFN treated group, these changes cannot be attributed to differences in neurodegeneration. SFN per se did not affect the glucose uptake at any given time point suggesting that SFN improves endogenous CNS ability to adapt to the epileptogenic insult. Furthermore, we had discovered that SFN improves blood flow and accelerates CBF response to electrical stimulation. Our findings suggest that SFN improves metabolic changes induced by SE which have been identified during epileptogenesis in various animal models of acquired epilepsy. |
| first_indexed | 2024-12-23T19:19:25Z |
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| language | English |
| last_indexed | 2024-12-23T19:19:25Z |
| publishDate | 2022-03-01 |
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| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-171f24c9c8ec49f0a804f1257081ff9a2022-12-21T17:34:13ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022022-03-011610.3389/fncel.2022.855161855161Sulforaphane Ameliorates Metabolic Changes Associated With Status Epilepticus in Immature RatsJan Daněk0Šárka Danačíková1David Kala2Jan Svoboda3Jan Svoboda4Sonam Kapoor5Antonín Pošusta6Jaroslava Folbergrová7Kateřina Tauchmannová8Tomáš Mráček9Jakub Otáhal10Jakub Otáhal11Institute of Physiology, Czech Academy of Sciences, Prague, CzechiaInstitute of Physiology, Czech Academy of Sciences, Prague, CzechiaInstitute of Physiology, Czech Academy of Sciences, Prague, CzechiaInstitute of Physiology, Czech Academy of Sciences, Prague, CzechiaDepartment of Pathophysiology, Second Faculty of Medicine, Charles University, Prague, CzechiaInstitute of Physiology, Czech Academy of Sciences, Prague, CzechiaInstitute of Physiology, Czech Academy of Sciences, Prague, CzechiaInstitute of Physiology, Czech Academy of Sciences, Prague, CzechiaInstitute of Physiology, Czech Academy of Sciences, Prague, CzechiaInstitute of Physiology, Czech Academy of Sciences, Prague, CzechiaInstitute of Physiology, Czech Academy of Sciences, Prague, CzechiaDepartment of Pathophysiology, Second Faculty of Medicine, Charles University, Prague, CzechiaStatus epilepticus (SE) is a common paediatric emergency with the highest incidence in the neonatal period and is a well-known epileptogenic insult. As previously established in various experimental and human studies, SE induces long-term alterations to brain metabolism, alterations that directly contribute to the development of epilepsy. To influence these changes, organic isothiocyanate compound sulforaphane (SFN) has been used in the present study for its known effect of enhancing antioxidative, cytoprotective, and metabolic cellular properties via the Nrf2 pathway. We have explored the effect of SFN in a model of acquired epilepsy induced by Li-Cl pilocarpine in immature rats (12 days old). Energy metabolites PCr, ATP, glucose, glycogen, and lactate were determined by enzymatic fluorimetric methods during the acute phase of SE. Protein expression was evaluated by Western blot (WB) analysis. Neuronal death was scored on the FluoroJadeB stained brain sections harvested 24 h after SE. To assess the effect of SFN on glucose metabolism we have performed a series of 18F-DG μCT/PET recordings 1 h, 1 day, and 3 weeks after the induction of SE. Responses of cerebral blood flow (CBF) to electrical stimulation and their influence by SFN were evaluated by laser Doppler flowmetry (LDF). We have demonstrated that the Nrf2 pathway is upregulated in the CNS of immature rats after SFN treatment. In the animals that had undergone SE, SFN was responsible for lowering glucose uptake in most regions 1 h after the induction of SE. Moreover, SFN partially reversed hypometabolism observed after 24 h and achieved full reversal at approximately 3 weeks after SE. Since no difference in cell death was observed in SFN treated group, these changes cannot be attributed to differences in neurodegeneration. SFN per se did not affect the glucose uptake at any given time point suggesting that SFN improves endogenous CNS ability to adapt to the epileptogenic insult. Furthermore, we had discovered that SFN improves blood flow and accelerates CBF response to electrical stimulation. Our findings suggest that SFN improves metabolic changes induced by SE which have been identified during epileptogenesis in various animal models of acquired epilepsy.https://www.frontiersin.org/articles/10.3389/fncel.2022.855161/fullstatus epilepticuspilocarpineimmature ratbrainμCT/PETglucose metabolism |
| spellingShingle | Jan Daněk Šárka Danačíková David Kala Jan Svoboda Jan Svoboda Sonam Kapoor Antonín Pošusta Jaroslava Folbergrová Kateřina Tauchmannová Tomáš Mráček Jakub Otáhal Jakub Otáhal Sulforaphane Ameliorates Metabolic Changes Associated With Status Epilepticus in Immature Rats Frontiers in Cellular Neuroscience status epilepticus pilocarpine immature rat brain μCT/PET glucose metabolism |
| title | Sulforaphane Ameliorates Metabolic Changes Associated With Status Epilepticus in Immature Rats |
| title_full | Sulforaphane Ameliorates Metabolic Changes Associated With Status Epilepticus in Immature Rats |
| title_fullStr | Sulforaphane Ameliorates Metabolic Changes Associated With Status Epilepticus in Immature Rats |
| title_full_unstemmed | Sulforaphane Ameliorates Metabolic Changes Associated With Status Epilepticus in Immature Rats |
| title_short | Sulforaphane Ameliorates Metabolic Changes Associated With Status Epilepticus in Immature Rats |
| title_sort | sulforaphane ameliorates metabolic changes associated with status epilepticus in immature rats |
| topic | status epilepticus pilocarpine immature rat brain μCT/PET glucose metabolism |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2022.855161/full |
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