Repeated episodes of postictal hypoxia are a mechanism for interictal cognitive impairments

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 seizur...

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Bibliographic Details
Published in:Scientific reports 2023-09, Vol.13 (1), p.15474-15474, Article 15474
Main Authors: Villa, Bianca R., Bhatt, Dhyey, Wolff, Marshal D., Addo-Osafo, Kwaku, Epp, Jonathan R., Teskey, G. Campbell
Format: Article
Language:English
Subjects:
631/378/1689/178
631/378/340
Acetaminophen
Calcium antagonists
Calcium channels
Calcium channels (L-type)
Cognitive ability
Comorbidity
Convulsions & seizures
Epilepsy
Humanities and Social Sciences
Hypoxia
multidisciplinary
Nifedipine
Science
Science (multidisciplinary)
Seizures
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-42741-7