In vivo dynamics of acidosis and oxidative stress in the acute phase of an ischemic stroke in a rodent model
Ischemic cerebral stroke is one of the leading causes of death and disability in humans. However, molecular processes underlying the development of this pathology remain poorly understood. There are major gaps in our understanding of metabolic changes that occur in the brain tissue during the early...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2021-12-01
|
| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231721003384 |
| _version_ | 1819174540770541568 |
|---|---|
| author | Ilya V. Kelmanson Arina G. Shokhina Daria A. Kotova Matvei S. Pochechuev Alexandra D. Ivanova Alexander I. Kostyuk Anastasiya S. Panova Anastasia A. Borodinova Maxim A. Solotenkov Evgeny A. Stepanov Roman I. Raevskii Aleksandr A. Moshchenko Valeriy V. Pak Yulia G. Ermakova Gijsbert J.C. van Belle Viktor Tarabykin Pavel M. Balaban Ilya V. Fedotov Andrei B. Fedotov Marcus Conrad Ivan Bogeski Dörthe M. Katschinski Thorsten R. Doeppner Mathias Bähr Aleksei M. Zheltikov Vsevolod V. Belousov Dmitry S. Bilan |
| author_facet | Ilya V. Kelmanson Arina G. Shokhina Daria A. Kotova Matvei S. Pochechuev Alexandra D. Ivanova Alexander I. Kostyuk Anastasiya S. Panova Anastasia A. Borodinova Maxim A. Solotenkov Evgeny A. Stepanov Roman I. Raevskii Aleksandr A. Moshchenko Valeriy V. Pak Yulia G. Ermakova Gijsbert J.C. van Belle Viktor Tarabykin Pavel M. Balaban Ilya V. Fedotov Andrei B. Fedotov Marcus Conrad Ivan Bogeski Dörthe M. Katschinski Thorsten R. Doeppner Mathias Bähr Aleksei M. Zheltikov Vsevolod V. Belousov Dmitry S. Bilan |
| author_sort | Ilya V. Kelmanson |
| collection | DOAJ |
| description | Ischemic cerebral stroke is one of the leading causes of death and disability in humans. However, molecular processes underlying the development of this pathology remain poorly understood. There are major gaps in our understanding of metabolic changes that occur in the brain tissue during the early stages of ischemia and reperfusion. In particular, it is generally accepted that both ischemia (I) and reperfusion (R) generate reactive oxygen species (ROS) that cause oxidative stress which is one of the main drivers of the pathology, although ROS generation during I/R was never demonstrated in vivo due to the lack of suitable methods. In the present study, we record for the first time the dynamics of intracellular pH and H2O2 during I/R in cultured neurons and during experimental stroke in rats using the latest generation of genetically encoded biosensors SypHer3s and HyPer7. We detect a buildup of powerful acidosis in the brain tissue that overlaps with the ischemic core from the first seconds of pathogenesis. At the same time, no significant H2O2 generation was found in the acute phase of ischemia/reperfusion. HyPer7 oxidation in the brain was detected only 24 h later. Comparison of in vivo experiments with studies on cultured neurons under I/R demonstrates that the dynamics of metabolic processes in these models significantly differ, suggesting that a cell culture is a poor predictor of metabolic events in vivo. |
| first_indexed | 2024-12-22T20:40:36Z |
| format | Article |
| id | doaj.art-1a45f757a0164abd98bbabfc20e1314f |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-22T20:40:36Z |
| publishDate | 2021-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-1a45f757a0164abd98bbabfc20e1314f2022-12-21T18:13:20ZengElsevierRedox Biology2213-23172021-12-0148102178In vivo dynamics of acidosis and oxidative stress in the acute phase of an ischemic stroke in a rodent modelIlya V. Kelmanson0Arina G. Shokhina1Daria A. Kotova2Matvei S. Pochechuev3Alexandra D. Ivanova4Alexander I. Kostyuk5Anastasiya S. Panova6Anastasia A. Borodinova7Maxim A. Solotenkov8Evgeny A. Stepanov9Roman I. Raevskii10Aleksandr A. Moshchenko11Valeriy V. Pak12Yulia G. Ermakova13Gijsbert J.C. van Belle14Viktor Tarabykin15Pavel M. Balaban16Ilya V. Fedotov17Andrei B. Fedotov18Marcus Conrad19Ivan Bogeski20Dörthe M. Katschinski21Thorsten R. Doeppner22Mathias Bähr23Aleksei M. Zheltikov24Vsevolod V. Belousov25Dmitry S. Bilan26M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia; Laboratory of Experimental Oncology, Pirogov Russian National Research Medical University, 117997, Moscow, RussiaM.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia; Laboratory of Experimental Oncology, Pirogov Russian National Research Medical University, 117997, Moscow, RussiaM.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, RussiaPhysics Department, International Laser Center, M.V. Lomonosov Moscow State University, Moscow, 119992, RussiaM.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia; Biological Department, M.V. Lomonosov Moscow State University, Moscow, 119992, RussiaM.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, RussiaM.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, RussiaInstitute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, 117485, RussiaPhysics Department, International Laser Center, M.V. Lomonosov Moscow State University, Moscow, 119992, RussiaPhysics Department, International Laser Center, M.V. Lomonosov Moscow State University, Moscow, 119992, Russia; Russian Quantum Center, Skolkovo, Moscow Region, 143025, RussiaM.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, RussiaFederal Center of Brain Research and Neurotechnologies, Federal Medical Biological Agency, Moscow, 117997, RussiaM.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, RussiaEuropean Molecular Biology Laboratory, Heidelberg, 69117, GermanyInstitute for Cardiovascular Physiology, University Medical Center Göttingen, Georg-August-University, Humboldtallee 23, 37073, Göttingen, GermanyInstitute of Cell Biology and Neurobiology, Charité - Universitätsmedizin Berlin, Berlin, 10117, GermanyInstitute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, 117485, RussiaPhysics Department, International Laser Center, M.V. Lomonosov Moscow State University, Moscow, 119992, Russia; Russian Quantum Center, Skolkovo, Moscow Region, 143025, Russia; Kazan Quantum Center, A.N. Tupolev Kazan National Research Technical University, Kazan, 420126, Russia; Department of Physics and Astronomy, Texas A&M University, College Station, TX, 77843, USAPhysics Department, International Laser Center, M.V. Lomonosov Moscow State University, Moscow, 119992, Russia; Russian Quantum Center, Skolkovo, Moscow Region, 143025, RussiaLaboratory of Experimental Oncology, Pirogov Russian National Research Medical University, 117997, Moscow, Russia; Helmholtz Zentrum München, Institute of Metabolism and Cell Death, Ingolstädter Landstr. 1, Neuherberg, 85764, GermanyInstitute for Cardiovascular Physiology, University Medical Center Göttingen, Georg-August-University, Humboldtallee 23, 37073, Göttingen, GermanyInstitute for Cardiovascular Physiology, University Medical Center Göttingen, Georg-August-University, Humboldtallee 23, 37073, Göttingen, GermanyDepartment of Neurology, University Medical Center Göttingen, Göttingen, 37075, Germany; Istanbul Medipol University, Research Institute for Health Sciences and Technologies (SABITA), Istanbul, Turkey; Istanbul Medipol University, School of Medicine, Dept. of Physiology, Istanbul, TurkeyDepartment of Neurology, University Medical Center Göttingen, Göttingen, 37075, GermanyPhysics Department, International Laser Center, M.V. Lomonosov Moscow State University, Moscow, 119992, Russia; Russian Quantum Center, Skolkovo, Moscow Region, 143025, Russia; Kazan Quantum Center, A.N. Tupolev Kazan National Research Technical University, Kazan, 420126, Russia; Department of Physics and Astronomy, Texas A&M University, College Station, TX, 77843, USAM.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia; Laboratory of Experimental Oncology, Pirogov Russian National Research Medical University, 117997, Moscow, Russia; Federal Center of Brain Research and Neurotechnologies, Federal Medical Biological Agency, Moscow, 117997, Russia; Institute for Cardiovascular Physiology, University Medical Center Göttingen, Georg-August-University, Humboldtallee 23, 37073, Göttingen, Germany; Corresponding author. Federal Center of Brain Research and Neurotechnologies, Federal Medical Biological Agency, Moscow, 117997, Russia.M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia; Laboratory of Experimental Oncology, Pirogov Russian National Research Medical University, 117997, Moscow, Russia; Corresponding author. M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia.Ischemic cerebral stroke is one of the leading causes of death and disability in humans. However, molecular processes underlying the development of this pathology remain poorly understood. There are major gaps in our understanding of metabolic changes that occur in the brain tissue during the early stages of ischemia and reperfusion. In particular, it is generally accepted that both ischemia (I) and reperfusion (R) generate reactive oxygen species (ROS) that cause oxidative stress which is one of the main drivers of the pathology, although ROS generation during I/R was never demonstrated in vivo due to the lack of suitable methods. In the present study, we record for the first time the dynamics of intracellular pH and H2O2 during I/R in cultured neurons and during experimental stroke in rats using the latest generation of genetically encoded biosensors SypHer3s and HyPer7. We detect a buildup of powerful acidosis in the brain tissue that overlaps with the ischemic core from the first seconds of pathogenesis. At the same time, no significant H2O2 generation was found in the acute phase of ischemia/reperfusion. HyPer7 oxidation in the brain was detected only 24 h later. Comparison of in vivo experiments with studies on cultured neurons under I/R demonstrates that the dynamics of metabolic processes in these models significantly differ, suggesting that a cell culture is a poor predictor of metabolic events in vivo.http://www.sciencedirect.com/science/article/pii/S2213231721003384Ischemic strokeIschemia/reperfusionHypoxia/reoxygenationIn vivo optical brain interrogationGenetically encoded fluorescent biosensorsHydrogen peroxide |
| spellingShingle | Ilya V. Kelmanson Arina G. Shokhina Daria A. Kotova Matvei S. Pochechuev Alexandra D. Ivanova Alexander I. Kostyuk Anastasiya S. Panova Anastasia A. Borodinova Maxim A. Solotenkov Evgeny A. Stepanov Roman I. Raevskii Aleksandr A. Moshchenko Valeriy V. Pak Yulia G. Ermakova Gijsbert J.C. van Belle Viktor Tarabykin Pavel M. Balaban Ilya V. Fedotov Andrei B. Fedotov Marcus Conrad Ivan Bogeski Dörthe M. Katschinski Thorsten R. Doeppner Mathias Bähr Aleksei M. Zheltikov Vsevolod V. Belousov Dmitry S. Bilan In vivo dynamics of acidosis and oxidative stress in the acute phase of an ischemic stroke in a rodent model Redox Biology Ischemic stroke Ischemia/reperfusion Hypoxia/reoxygenation In vivo optical brain interrogation Genetically encoded fluorescent biosensors Hydrogen peroxide |
| title | In vivo dynamics of acidosis and oxidative stress in the acute phase of an ischemic stroke in a rodent model |
| title_full | In vivo dynamics of acidosis and oxidative stress in the acute phase of an ischemic stroke in a rodent model |
| title_fullStr | In vivo dynamics of acidosis and oxidative stress in the acute phase of an ischemic stroke in a rodent model |
| title_full_unstemmed | In vivo dynamics of acidosis and oxidative stress in the acute phase of an ischemic stroke in a rodent model |
| title_short | In vivo dynamics of acidosis and oxidative stress in the acute phase of an ischemic stroke in a rodent model |
| title_sort | in vivo dynamics of acidosis and oxidative stress in the acute phase of an ischemic stroke in a rodent model |
| topic | Ischemic stroke Ischemia/reperfusion Hypoxia/reoxygenation In vivo optical brain interrogation Genetically encoded fluorescent biosensors Hydrogen peroxide |
| url | http://www.sciencedirect.com/science/article/pii/S2213231721003384 |
| work_keys_str_mv | AT ilyavkelmanson invivodynamicsofacidosisandoxidativestressintheacutephaseofanischemicstrokeinarodentmodel AT arinagshokhina invivodynamicsofacidosisandoxidativestressintheacutephaseofanischemicstrokeinarodentmodel AT dariaakotova invivodynamicsofacidosisandoxidativestressintheacutephaseofanischemicstrokeinarodentmodel AT matveispochechuev invivodynamicsofacidosisandoxidativestressintheacutephaseofanischemicstrokeinarodentmodel AT alexandradivanova invivodynamicsofacidosisandoxidativestressintheacutephaseofanischemicstrokeinarodentmodel AT alexanderikostyuk invivodynamicsofacidosisandoxidativestressintheacutephaseofanischemicstrokeinarodentmodel AT anastasiyaspanova invivodynamicsofacidosisandoxidativestressintheacutephaseofanischemicstrokeinarodentmodel AT anastasiaaborodinova invivodynamicsofacidosisandoxidativestressintheacutephaseofanischemicstrokeinarodentmodel AT maximasolotenkov invivodynamicsofacidosisandoxidativestressintheacutephaseofanischemicstrokeinarodentmodel AT evgenyastepanov invivodynamicsofacidosisandoxidativestressintheacutephaseofanischemicstrokeinarodentmodel AT romaniraevskii invivodynamicsofacidosisandoxidativestressintheacutephaseofanischemicstrokeinarodentmodel AT aleksandramoshchenko invivodynamicsofacidosisandoxidativestressintheacutephaseofanischemicstrokeinarodentmodel AT valeriyvpak invivodynamicsofacidosisandoxidativestressintheacutephaseofanischemicstrokeinarodentmodel AT yuliagermakova invivodynamicsofacidosisandoxidativestressintheacutephaseofanischemicstrokeinarodentmodel AT gijsbertjcvanbelle invivodynamicsofacidosisandoxidativestressintheacutephaseofanischemicstrokeinarodentmodel AT viktortarabykin invivodynamicsofacidosisandoxidativestressintheacutephaseofanischemicstrokeinarodentmodel AT pavelmbalaban invivodynamicsofacidosisandoxidativestressintheacutephaseofanischemicstrokeinarodentmodel AT ilyavfedotov invivodynamicsofacidosisandoxidativestressintheacutephaseofanischemicstrokeinarodentmodel AT andreibfedotov invivodynamicsofacidosisandoxidativestressintheacutephaseofanischemicstrokeinarodentmodel AT marcusconrad invivodynamicsofacidosisandoxidativestressintheacutephaseofanischemicstrokeinarodentmodel AT ivanbogeski invivodynamicsofacidosisandoxidativestressintheacutephaseofanischemicstrokeinarodentmodel AT dorthemkatschinski invivodynamicsofacidosisandoxidativestressintheacutephaseofanischemicstrokeinarodentmodel AT thorstenrdoeppner invivodynamicsofacidosisandoxidativestressintheacutephaseofanischemicstrokeinarodentmodel AT mathiasbahr invivodynamicsofacidosisandoxidativestressintheacutephaseofanischemicstrokeinarodentmodel AT alekseimzheltikov invivodynamicsofacidosisandoxidativestressintheacutephaseofanischemicstrokeinarodentmodel AT vsevolodvbelousov invivodynamicsofacidosisandoxidativestressintheacutephaseofanischemicstrokeinarodentmodel AT dmitrysbilan invivodynamicsofacidosisandoxidativestressintheacutephaseofanischemicstrokeinarodentmodel |