Influences of pituitary-adrenal hormones on kindling

Rose, Robert P.; Morell, Frank; Hoeppner, Thomas J.

doi:10.1016/0006-8993(79)91032-1

Cited by 19 publications

(7 citation statements)

References 22 publications

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“…A great deal of evidence already implicates CORT in the mechanism connecting stress in adulthood to epileptogenesis [49]: elevating CORT augments epileptogenesis and seizures in several animal models [7], [8], [9], [13], [50], [51], [52], [53], an effect reversed by antagonist of glucocorticoid and mineralocorticoid receptors [8]; whereas kindling is slowed in adrenalectomised or hypophysectomised rats [10], [11], [12], [13]. Thus, a direct effect of the enhanced CORT release post-seizures is a strong candidate explanation of the accelerated kindling epileptogenesis in MS exposed rats.…”

Section: Discussionmentioning

confidence: 99%

“…For stressors in adult life, studies are consistent in reporting that stress or stress mediators enhance epileptogenesis in experimental models [6]. For example, administering exogenous corticosterone (CORT) aggravates kindling epileptogenesis [7], [8], [9], an effect reversed using antagonists of glucocorticoid and mineralocorticoid receptors [8]; and kindling is slowed in adrenalectomised or hypophysectomised rats [10], [11], [12], [13]. Recently it has become increasingly clear that stress in early life can result in enduring vulnerability to epileptogenesis in adult animals [14], [15], [16], however, experimental data about mechanisms underlying such effects remain sparse.…”

Section: Introductionmentioning

confidence: 98%

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Early Life Stress Enhancement of Limbic Epileptogenesis in Adult Rats: Mechanistic Insights

et al. 2011

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BackgroundExposure to early postnatal stress is known to hasten the progression of kindling epileptogenesis in adult rats. Despite the significance of this for understanding mesial temporal lobe epilepsy (MTLE) and its associated psychopathology, research findings regarding underlying mechanisms are sparse. Of several possibilities, one important candidate mechanism is early life ‘programming’ of the hypothalamic-pituitary-adrenal (HPA) axis by postnatal stress. Elevated corticosterone (CORT) in turn has consequences for neurogenesis and cell death relevant to epileptogenesis. Here we tested the hypotheses that MS would augment seizure-related corticosterone (CORT) release and enhance neuroplastic changes in the hippocampus.Methodology/Principal FindingsEight-week old Wistar rats, previously exposed on postnatal days 2–14 to either maternal separation stress (MS) or control brief early handling (EH), underwent rapid amygdala kindling. We measured seizure-induced serum CORT levels and post-kindling neurogenesis (using BrdU). Three weeks post-kindling, rats were euthanized for histology of the hippocampal CA3c region (pyramidal cell counts) and dentate gyrus (DG) (to count BrdU-labelled cells and measure mossy fibre sprouting). As in our previous studies, rats exposed to MS had accelerated kindling rates in adulthood. Female MS rats had heightened CORT responses during and after kindling (p<0.05), with a similar trend in males. In both sexes total CA3c pyramidal cell numbers were reduced in MS vs. EH rats post-kindling (p = 0.002). Dentate granule cell neurogenesis in female rats was significantly increased post-kindling in MS vs. EH rats.Conclusions/SignificanceThese data demonstrate that early life stress results in enduring enhancement of HPA axis responses to limbic seizures, with increased hippocampal CA3c cell loss and augmented neurogenesis, in a sex-dependent pattern. This implicates important candidate mechanisms through which early life stress may promote vulnerability to limbic epileptogenesis in rats as well as to human MTLE and its associated psychiatric disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Early Life Stress Enhancement of Limbic Epileptogenesis in Adult Rats: Mechanistic Insights

et al. 2011

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“…Pituitary–adrenal hormones have long been known to affect epileptogenesis (Aird and Gordan, 1951; Rose et al, 1979; Weiss et al, 1993; Joëls, 2009; Borekci et al, 2010). Acute stress raises seizure threshold in animals, but chronic stress is known to be a clear risk factor for precipitating seizures in patients with epilepsies.…”

Section: Role Of Steroid Hormones In Epileptogenesismentioning

confidence: 99%

Role of hormones and neurosteroids in epileptogenesis

Reddy

2013

Front. Cell. Neurosci.

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This article describes the emerging evidence of hormonal influence on epileptogenesis, which is a process whereby a brain becomes progressively epileptic due to an initial precipitating event of diverse origin such as brain injury, stroke, infection, or prolonged seizures. The molecular mechanisms underlying the development of epilepsy are poorly understood. Neuroinflammation and neurodegeneration appear to trigger epileptogenesis. There is an intense search for drugs that truly prevent the development of epilepsy in people at risk. Hormones play an important role in children and adults with epilepsy. Corticosteroids, progesterone, estrogens, and neurosteroids have been shown to affect seizure activity in animal models and in clinical studies. However, the impact of hormones on epileptogenesis has not been investigated widely. There is emerging new evidence that progesterone, neurosteroids, and endogenous hormones may play a role in regulating the epileptogenesis. Corticosterone has excitatory effects and triggers epileptogenesis in animal models. Progesterone has disease-modifying activity in epileptogenic models. The antiepileptogenic effect of progesterone has been attributed to its conversion to neurosteroids, which binds to GABA-A receptors and enhances phasic and tonic inhibition in the brain. Neurosteroids are robust anticonvulsants. There is pilot evidence that neurosteroids may have antiepileptogenic properties. Future studies may generate new insight on the disease-modifying potential of hormonal agents and neurosteroids in epileptogenesis.

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“…In kindling models, CORT manipulations are primarily proconvulsive, but a few studies have shown either anticonvulsive effects or no effects at all ( Table 1). One of the studies showing anticonvulsive effects involved the removal of the pituitary, which alters far more than the HPA axis (Rose et al, 1979), and two studies used cortisone, a CORT metabolite, instead of CORT (Rose and Bridger, 1982). It should be noted that many experimental variables differed between the kindling studies as shown in Table 1: CORT administration was acute or chronic, adrenalectomy was performed either before or after the kindling process, CORT was administered via different methods and at different dosages, and different strains of rats were used.…”

Section: Effects Of Corticosterone On Seizuresmentioning

confidence: 99%

Stress and Epilepsy: Multiple Models, Multiple Outcomes

Sawyer

Escayg

2010

Journal of Clinical Neurophysiology

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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.

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Influences of pituitary-adrenal hormones on kindling

Cited by 19 publications

References 22 publications

Early Life Stress Enhancement of Limbic Epileptogenesis in Adult Rats: Mechanistic Insights

Early Life Stress Enhancement of Limbic Epileptogenesis in Adult Rats: Mechanistic Insights

Role of hormones and neurosteroids in epileptogenesis

Stress and Epilepsy: Multiple Models, Multiple Outcomes

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