Repeated episodes of postictal hypoxia are a mechanism for interictal cognitive impairments
Abstract Comorbidities during the period between seizures present a significant challenge for individuals with epilepsy. Despite their clinical relevance, the pathophysiology of the interictal symptomatology is largely unknown. Postictal severe hypoxia (PIH) in those brain regions participating in t...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-42741-7 |
| _version_ | 1827634766198865920 |
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| author | Bianca R. Villa Dhyey Bhatt Marshal D. Wolff Kwaku Addo-Osafo Jonathan R. Epp G. Campbell Teskey |
| author_facet | Bianca R. Villa Dhyey Bhatt Marshal D. Wolff Kwaku Addo-Osafo Jonathan R. Epp G. Campbell Teskey |
| author_sort | Bianca R. Villa |
| collection | DOAJ |
| description | Abstract Comorbidities during the period between seizures present a significant challenge for individuals with epilepsy. Despite their clinical relevance, the pathophysiology of the interictal symptomatology is largely unknown. Postictal severe hypoxia (PIH) in those brain regions participating in the seizure has been indicated as a mechanism underlying several negative postictal manifestations. It is unknown how repeated episodes of PIH affect interictal symptoms in epilepsy. Using a rat model, we observed that repeated seizures consistently induced episodes of PIH that become increasingly severe with each seizure occurrence. Additionally, recurrent seizure activity led to decreased levels of oxygen in the hippocampus during the interictal period. However, these reductions were prevented when we repeatedly blocked PIH using either the COX-inhibitor acetaminophen or the L-type calcium channel antagonist nifedipine. Moreover, we found that interictal cognitive deficits caused by seizures were completely alleviated by repeated attenuation of PIH events. Lastly, mitochondrial dysfunction may contribute to the observed pathological outcomes during the interictal period. These findings provide evidence that seizure-induced hypoxia may play a crucial role in several aspects of epilepsy. Consequently, developing and implementing treatments that specifically target and prevent PIH could potentially offer significant benefits for individuals with refractory epilepsy. |
| first_indexed | 2024-03-09T15:18:51Z |
| format | Article |
| id | doaj.art-c1c8361e8030463093a76d1490ae5292 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T15:18:51Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-c1c8361e8030463093a76d1490ae52922023-11-26T12:57:06ZengNature PortfolioScientific Reports2045-23222023-09-0113111110.1038/s41598-023-42741-7Repeated episodes of postictal hypoxia are a mechanism for interictal cognitive impairmentsBianca R. Villa0Dhyey Bhatt1Marshal D. Wolff2Kwaku Addo-Osafo3Jonathan R. Epp4G. Campbell Teskey5Cumming School of Medicine, Hotchkiss Brain Institute, University of CalgaryCumming School of Medicine, Hotchkiss Brain Institute, University of CalgaryCumming School of Medicine, Hotchkiss Brain Institute, University of CalgaryCumming School of Medicine, Hotchkiss Brain Institute, University of CalgaryCumming School of Medicine, Hotchkiss Brain Institute, University of CalgaryCumming School of Medicine, Hotchkiss Brain Institute, University of CalgaryAbstract Comorbidities during the period between seizures present a significant challenge for individuals with epilepsy. Despite their clinical relevance, the pathophysiology of the interictal symptomatology is largely unknown. Postictal severe hypoxia (PIH) in those brain regions participating in the seizure has been indicated as a mechanism underlying several negative postictal manifestations. It is unknown how repeated episodes of PIH affect interictal symptoms in epilepsy. Using a rat model, we observed that repeated seizures consistently induced episodes of PIH that become increasingly severe with each seizure occurrence. Additionally, recurrent seizure activity led to decreased levels of oxygen in the hippocampus during the interictal period. However, these reductions were prevented when we repeatedly blocked PIH using either the COX-inhibitor acetaminophen or the L-type calcium channel antagonist nifedipine. Moreover, we found that interictal cognitive deficits caused by seizures were completely alleviated by repeated attenuation of PIH events. Lastly, mitochondrial dysfunction may contribute to the observed pathological outcomes during the interictal period. These findings provide evidence that seizure-induced hypoxia may play a crucial role in several aspects of epilepsy. Consequently, developing and implementing treatments that specifically target and prevent PIH could potentially offer significant benefits for individuals with refractory epilepsy.https://doi.org/10.1038/s41598-023-42741-7 |
| spellingShingle | Bianca R. Villa Dhyey Bhatt Marshal D. Wolff Kwaku Addo-Osafo Jonathan R. Epp G. Campbell Teskey Repeated episodes of postictal hypoxia are a mechanism for interictal cognitive impairments Scientific Reports |
| title | Repeated episodes of postictal hypoxia are a mechanism for interictal cognitive impairments |
| title_full | Repeated episodes of postictal hypoxia are a mechanism for interictal cognitive impairments |
| title_fullStr | Repeated episodes of postictal hypoxia are a mechanism for interictal cognitive impairments |
| title_full_unstemmed | Repeated episodes of postictal hypoxia are a mechanism for interictal cognitive impairments |
| title_short | Repeated episodes of postictal hypoxia are a mechanism for interictal cognitive impairments |
| title_sort | repeated episodes of postictal hypoxia are a mechanism for interictal cognitive impairments |
| url | https://doi.org/10.1038/s41598-023-42741-7 |
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