Chronic Hyperhomocysteinemia Impairs CSD Propagation and Induces Cortical Damage in a Rat Model of Migraine with Aura
Hyperhomocysteinemia (hHCY) is a metabolic disorder characterized by elevated levels of homocysteine in plasma. hHCY correlates with a high risk of migraine headaches, especially migraine with aura. Cortical spreading depression (CSD) is a wave of depolarization passing through neurons and glial cel...
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2024-10-01
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| author | Elena Gerasimova Daniel Enikeev Aleksey Yakovlev Andrey Zakharov Guzel Sitdikova |
| author_facet | Elena Gerasimova Daniel Enikeev Aleksey Yakovlev Andrey Zakharov Guzel Sitdikova |
| author_sort | Elena Gerasimova |
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| description | Hyperhomocysteinemia (hHCY) is a metabolic disorder characterized by elevated levels of homocysteine in plasma. hHCY correlates with a high risk of migraine headaches, especially migraine with aura. Cortical spreading depression (CSD) is a wave of depolarization passing through neurons and glial cells of the cortex and is considered an electrophysiological correlate of migraine aura. The aim of the present study was to analyze neuronal activity and CSD in the somatosensory cortex of rats in vivo with prenatal hHCY and to assess cortex viability after 2 h of CSD generation. Female rats were fed a diet high in methionine, and their offspring with high homocysteine levels in plasma were further used in experiments. Recurrent CSD was evoked by local KCl application on the dura surface. Neuronal viability was assessed by measuring the activity of lactate dehydrogenase (LDH) in the brain and 2,3,5-triphenyltetrazolium chloride staining of the somatosensory cortex after two hours of CSD generation. Animals with hHCY exhibited higher neuronal activity, and more CSDs were generated in response to KCl, indicating higher cortical excitability. Propagation of recurrent CSD was impaired in supragranular cortical layers, and the recovery of multiple unit activity and evoked sensory potentials after CSD was delayed in the hHCY group. Finally, in animals with prenatal hHCY, an ischemic focus was identified as a consequence of multiple CSDs, along with elevated levels of LDH activity in brain tissues, suggestive of diminished neuronal viability. These findings imply that prolonged elevated levels of homocysteine may not only predispose to migraine with aura but also potentially elevate the risk of migrainous infarction. |
| format | Article |
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| institution | Kabale University |
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| series | Biomolecules |
| spelling | doaj-art-0d99c8af6f91403d884bd482d2854a832024-11-26T17:54:03ZengMDPI AGBiomolecules2218-273X2024-10-011411137910.3390/biom14111379Chronic Hyperhomocysteinemia Impairs CSD Propagation and Induces Cortical Damage in a Rat Model of Migraine with AuraElena Gerasimova0Daniel Enikeev1Aleksey Yakovlev2Andrey Zakharov3Guzel Sitdikova4Department of Neuroscience, Sirius University of Science and Technology, 354340 Sirius, RussiaDepartment of Neuroscience, Sirius University of Science and Technology, 354340 Sirius, RussiaDepartment of Human and Animal Physiology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlevskaya Str., 420008 Kazan, RussiaDepartment of Normal Physiology, Kazan State Medical University, 49 Butlerova Str., 420012 Kazan, RussiaDepartment of Human and Animal Physiology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlevskaya Str., 420008 Kazan, RussiaHyperhomocysteinemia (hHCY) is a metabolic disorder characterized by elevated levels of homocysteine in plasma. hHCY correlates with a high risk of migraine headaches, especially migraine with aura. Cortical spreading depression (CSD) is a wave of depolarization passing through neurons and glial cells of the cortex and is considered an electrophysiological correlate of migraine aura. The aim of the present study was to analyze neuronal activity and CSD in the somatosensory cortex of rats in vivo with prenatal hHCY and to assess cortex viability after 2 h of CSD generation. Female rats were fed a diet high in methionine, and their offspring with high homocysteine levels in plasma were further used in experiments. Recurrent CSD was evoked by local KCl application on the dura surface. Neuronal viability was assessed by measuring the activity of lactate dehydrogenase (LDH) in the brain and 2,3,5-triphenyltetrazolium chloride staining of the somatosensory cortex after two hours of CSD generation. Animals with hHCY exhibited higher neuronal activity, and more CSDs were generated in response to KCl, indicating higher cortical excitability. Propagation of recurrent CSD was impaired in supragranular cortical layers, and the recovery of multiple unit activity and evoked sensory potentials after CSD was delayed in the hHCY group. Finally, in animals with prenatal hHCY, an ischemic focus was identified as a consequence of multiple CSDs, along with elevated levels of LDH activity in brain tissues, suggestive of diminished neuronal viability. These findings imply that prolonged elevated levels of homocysteine may not only predispose to migraine with aura but also potentially elevate the risk of migrainous infarction.https://www.mdpi.com/2218-273X/14/11/1379migraine with aurahyperhomocysteinemiacortical spreading depressionsomatosensory cortexlactate dehydrogenasecortex viability |
| spellingShingle | Elena Gerasimova Daniel Enikeev Aleksey Yakovlev Andrey Zakharov Guzel Sitdikova Chronic Hyperhomocysteinemia Impairs CSD Propagation and Induces Cortical Damage in a Rat Model of Migraine with Aura Biomolecules migraine with aura hyperhomocysteinemia cortical spreading depression somatosensory cortex lactate dehydrogenase cortex viability |
| title | Chronic Hyperhomocysteinemia Impairs CSD Propagation and Induces Cortical Damage in a Rat Model of Migraine with Aura |
| title_full | Chronic Hyperhomocysteinemia Impairs CSD Propagation and Induces Cortical Damage in a Rat Model of Migraine with Aura |
| title_fullStr | Chronic Hyperhomocysteinemia Impairs CSD Propagation and Induces Cortical Damage in a Rat Model of Migraine with Aura |
| title_full_unstemmed | Chronic Hyperhomocysteinemia Impairs CSD Propagation and Induces Cortical Damage in a Rat Model of Migraine with Aura |
| title_short | Chronic Hyperhomocysteinemia Impairs CSD Propagation and Induces Cortical Damage in a Rat Model of Migraine with Aura |
| title_sort | chronic hyperhomocysteinemia impairs csd propagation and induces cortical damage in a rat model of migraine with aura |
| topic | migraine with aura hyperhomocysteinemia cortical spreading depression somatosensory cortex lactate dehydrogenase cortex viability |
| url | https://www.mdpi.com/2218-273X/14/11/1379 |
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