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Does Stress Trigger Seizures? Evidence from Experimental Models

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Psychiatric and Behavioral Aspects of Epilepsy

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 55))

Abstract

This chapter describes the experimental evidence of stress modulation of epileptic seizures and the potential role of corticosteroids and neurosteroids in regulating stress-linked seizure vulnerability. Epilepsy is a chronic neurological disorder that is characterized by repeated seizures. There are many potential causes for epilepsy, including genetic predispositions, infections, brain injury, and neurotoxicity. Stress is a known precipitating factor for seizures in individuals suffering from epilepsy. Severe acute stress and persistent exposure to stress may increase susceptibility to seizures, thereby resulting in a higher frequency of seizures. This occurs through the stress-mediated release of cortisol, which has both excitatory and proconvulsant properties. Stress also causes the release of endogenous neurosteroids from central and adrenal sources. Neurosteroids such as allopregnanolone and THDOC, which are allosteric modulators of GABA-A receptors, are powerful anticonvulsants and neuroprotectants. Acute stress increases the release of neurosteroids, while chronic stress is associated with severe neurosteroid depletion and reduced inhibition in the brain. This diminished inhibition occurs largely as a result of neurosteroid deficiencies. Thus, exogenous administration of neurosteroids (neurosteroid replacement therapy) may offer neuroprotection in epilepsy. Synthetic neurosteroid could offer a rational approach to control neurosteroid-sensitive, stress-related epileptic seizures.

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Abbreviations

3α-HSOR:

3α-hydroxysteroid oxidoreductase

ACTH:

Adrenocorticotrophic hormone

AED:

Anti-epileptic drug

AP:

Allopregnanolone (brexanolone)

CRH:

Corticotropin releasing hormone

DHDOC:

5α-dihydro-deoxycorticosterone

DHEAS:

Dehydroepiandrosterone sulfate

DOC:

Deoxycorticosterone

GAS:

General adaptation syndrome

HPA:

Hypothalamic-pituitary-adrenal

PS:

Pregnenolone sulfate

PTSD:

Post-traumatic stress disorder

THDOC:

Allotetrahydro-deoxycorticosterone

TLE:

Temporal lobe epilepsy

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Acknowledgments

This work was supported by the National Institutes of Health Grants U01 NS083460, R21 NS076426 and R21 NS099009 (to D.S.R.).

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Nothing declared.

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Author notes

  1. Wesley Thompson and Gianmarco Calderara contributed equally to this work.

Authors and Affiliations

  1. Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University Health Science Center, Bryan, TX, USA

    Doodipala Samba Reddy, Wesley Thompson & Gianmarco Calderara

Authors
  1. Doodipala Samba Reddy
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  2. Wesley Thompson
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  3. Gianmarco Calderara
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Corresponding author

Correspondence to Doodipala Samba Reddy .

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Editors and Affiliations

  1. Department of Neuroscience Central Clinical School, Monash University, Melbourne, Australia

    Nigel C. Jones

  2. Miller School of Medicine, University of Miami, Miami, FL, USA

    Andres M. Kanner

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Reddy, D.S., Thompson, W., Calderara, G. (2020). Does Stress Trigger Seizures? Evidence from Experimental Models. In: Jones, N.C., Kanner, A.M. (eds) Psychiatric and Behavioral Aspects of Epilepsy . Current Topics in Behavioral Neurosciences, vol 55. Springer, Cham. https://doi.org/10.1007/7854_2020_191

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