Caffeine Exacerbates Postictal Hypoxia

Phillips, T. J.; Gom, Renaud C.; Wolff, Marshal D.; Teskey, G. Campbell

doi:10.1016/j.neuroscience.2019.09.025

Cited by 11 publications

(8 citation statements)

References 100 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In agreement with this mechanism, caffeine, which is a well-known vasoconstrictor, has been shown to aggravate postictal hypoxia in rodents. 105 This mechanism possibly acts via antagonistic effects on adenosine receptors.…”

Section: Hypoperfusion and Hypoxia (T2)mentioning

confidence: 99%

The postictal state — What do we know?

et al. 2020

View full text Add to dashboard Cite

This narrative review provides a broad and comprehensive overview of the most important discoveries on the postictal state over the past decades as well as recent developments. After a description and definition of the postictal state, we discuss postictal sypmtoms, their clinical manifestations, and related findings. Moreover, pathophysiological advances are reviewed, followed by current treatment options. K E Y W O R D S epilepsy, postictal suppression, postictal symptoms, postictal treatment, SUDEPThis is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

show abstract

Section: Hypoperfusion and Hypoxia (T2)mentioning

confidence: 99%

The postictal state — What do we know?

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The vasodilating effect of seizure-induced adenosine surging may attenuate the postictal dysfunction elicited by cerebral vasoconstriction ( Figure 2 and Table 1 ). This hypothesis is supported by the finding that adenosine antagonism worsens the cerebral hypoxia caused by postictal hypoperfusion ( Phillips et al, 2019 ). Taken together, the seizure-induced adenosine surge is beneficial in its effects on seizure termination, prevention of epileptogenesis, vasodilation, and neuroprotection under hypoxic conditions ( Figure 2 and Table 1 ).…”

Section: The Goodmentioning

confidence: 78%

“…Adenosine acts as a cerebral vasodilator and may alleviate the deleterious effects of seizure-induced vasoconstriction ( Morii et al, 1986 ; Arrigoni et al, 2005 ). Furthermore, adenosine signaling is neuroprotective under hypoxic conditions ( Bjorklund et al, 2008 ; Phillips et al, 2019 ). As a result, seizure-induced adenosine surging and the increased tissue tone of adenosine are “good” for patient health.…”

Section: Introductionmentioning

confidence: 99%

The Good, the Bad, and the Deadly: Adenosinergic Mechanisms Underlying Sudden Unexpected Death in Epilepsy

et al. 2021

View full text Add to dashboard Cite

Adenosine is an inhibitory modulator of neuronal excitability. Neuronal activity results in increased adenosine release, thereby constraining excessive excitation. The exceptionally high neuronal activity of a seizure results in a surge in extracellular adenosine to concentrations many-fold higher than would be observed under normal conditions. In this review, we discuss the multifarious effects of adenosine signaling in the context of epilepsy, with emphasis on sudden unexpected death in epilepsy (SUDEP). We describe and categorize the beneficial, detrimental, and potentially deadly aspects of adenosine signaling. The good or beneficial characteristics of adenosine signaling in the context of seizures include: (1) its direct effect on seizure termination and the prevention of status epilepticus; (2) the vasodilatory effect of adenosine, potentially counteracting postictal vasoconstriction; (3) its neuroprotective effects under hypoxic conditions; and (4) its disease modifying antiepileptogenic effect. The bad or detrimental effects of adenosine signaling include: (1) its capacity to suppress breathing and contribute to peri-ictal respiratory dysfunction; (2) its contribution to postictal generalized EEG suppression (PGES); (3) the prolonged increase in extracellular adenosine following spreading depolarization waves may contribute to postictal neuronal dysfunction; (4) the excitatory effects of A2A receptor activation is thought to exacerbate seizures in some instances; and (5) its potential contributions to sleep alterations in epilepsy. Finally, the adverse effects of adenosine signaling may potentiate a deadly outcome in the form of SUDEP by suppressing breathing and arousal in the postictal period. Evidence from animal models suggests that excessive postictal adenosine signaling contributes to the pathophysiology of SUDEP. The goal of this review is to discuss the beneficial, harmful, and potentially deadly roles that adenosine plays in the context of epilepsy and to identify crucial gaps in knowledge where further investigation is necessary. By better understanding adenosine dynamics, we may gain insights into the treatment of epilepsy and the prevention of SUDEP.

show abstract

“…Rats were unilaterally stimulated (60 Hz, 1 s train of 1 ms biphasic rectangular wave pulses) by using small incremental steps of current (50 µA; Grass S88 stimulator, Natus Neurology, Warwick, RI) in the ventral hippocampus to determine afterdischarge thresholds (ADTs; defined as the minimum amount of stimulus that evokes an electrographic seizure). Then, the rats were repeatedly stimulated once a day at an intensity of 100 µA above threshold to ensure that a seizure was elicited every time for 20 consecutive days—typical number of stimulations that lead to reliable postictal hypoxia profiles regardless of seizure severity 24 . Electrographic seizures without accompanying clinical manifestations were counted as seizures.…”

Section: Methodsmentioning

confidence: 99%

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

Villa,

Bhatt,

Wolff

et al. 2023

Sci Rep

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Caffeine Exacerbates Postictal Hypoxia

Cited by 11 publications

References 100 publications

The postictal state — What do we know?

The postictal state — What do we know?

The Good, the Bad, and the Deadly: Adenosinergic Mechanisms Underlying Sudden Unexpected Death in Epilepsy

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

Contact Info

Product

Resources

About