Stress and Epilepsy: Multiple Models, Multiple Outcomes

Abstract

Human studies show a link between stress and epilepsy, with stress causing an increase in seizure frequency and severity in patients with epilepsy. Many different animal model systems have been used to better understand this connection and the possible mechanisms involved. This review highlights the results of such studies relating stress and seizure susceptibility, with a focus on the hypothalamic-pituitary-adrenal axis and its relationship to seizure generation. The effects of hypothalamic-pituitary-adrenal axis mediators, acute stress, chronic stress, and early life stress on the seizure phenotype are summarized. Results suggest that stress has both anticonvulsive and proconvulsive properties, depending on the animal strain and the stress/seizure induction paradigm used. Attempts to interpret the stress-epilepsy literature must take these variables into account. The growing availability of genetically modified mice that carry either human epilepsy mutations or mutations in stress pathway genes now provide the opportunity to examine the relationship between stress and epilepsy more directly.

Postnatal Steroids and Febrile Seizure Susceptibility in Preterm Children

“…33 These abnormal changes are supported by the observation that early-life stress facilitates seizure development. 34 This effect on seizure development can be mediated by corticosterone: the facilitating effect of corticosterone on chemicalinduced status epilepticus in rat pups is inhibited by a corticosterone synthesis blocker, thus confirming the crucial role of corticosterone in seizure susceptibility. 35 High corticosterone levels in early life are believed to irreversibly impair the inhibitory control of the hypothalamic-pituitary-adrenal axis; the disinhibition of this chronic stress axis may induce upregulation of CRH from the paraventricular nucleus.…”

Beneficial effects of a ketamine/atropine combination in soman-poisoned rats under a neutral thermal environment

“…accompanied by a robust increase in blood corticosterone concentrations (Mazarati et al, 2009). Inter-relations between stress and seizures are well known (Haut et al, 2003;Lai and Trimble, 1997;Sawyer and Escayg, 2010) although the details of such interaction remain elusive. Hyperglycemia was observed in soman-intoxicated rats exhibiting signs of toxicity such as chewing, salivation, muscle fasciculations or tremors (Fletcher et al, 1988;Jovic, 1974;Maickel et al, 1990;Rahimi and Abdollahi, 2007).…”

Stress and epilepsy: fact or fiction, and what can we do about it?

“…Interestingly, preclinical animal studies suggest that acute stress protects against seizures, although this varies in different models 18. The largest group of experiments is in rodent models exposed to swim stress that creates both physical and psychological stress.…”