Sex Differences in the Epilepsies and Associated Comorbidities: Implications for Use and Development of Pharmacotherapies

Christian, Catherine A.; Reddy, Doodipala Samba; Maguire, Jamie; Forcelli, Patrick A.

doi:10.1124/pr.119.017392

Cited by 75 publications

(83 citation statements)

References 508 publications

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“…That female rats fared better than male rats in spatial cognition post‐ELS was surprising, illustrating the importance of exploring sex as a variable for cognitive outcome post‐ELS 30 . Most prior studies have used only male rats, or found sex differences in cognitive outcomes when seizures were administered in adults 38 .…”

Section: Discussionmentioning

confidence: 99%

“…That female rats fared better than male rats in spatial cognition post-ELS was surprising, illustrating the importance of exploring sex as a variable for cognitive outcome post-ELS. 30 Most prior studies have used only male rats, or found sex differences in cognitive outcomes when seizures were administered in adults. 38 Using a comparable approach with ELS induction, Akman et al 39 found that three episodes of kainic acid-induced status epilepticus on P4-P6 caused more transient learning delays in the Barnes maze on P16-P19 in males but not females.…”

Section: Discussionmentioning

confidence: 99%

“…However, the effects of early life seizures (ELSs) on the hippocampus–mPFC circuit in relation to spatial memory deficits 27 remain poorly understood. Moreover, ELS cognitive outcome variables such as dynamic coordination efficacy in the hippocampus–mPFC circuit and sex 28–30 have not been studied.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, ELS cognitive outcome variables such as dynamic coordination efficacy in the hippocampus-mPFC circuit and sex [28][29][30] have not been studied.…”

Section: Introductionmentioning

confidence: 99%

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Effects of early life seizures on coordination of hippocampal–prefrontal networks: Influence of sex and dynamic brain states

et al. 2021

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Objective: Early life seizures (ELSs) alter activity-dependent maturation of neuronal circuits underlying learning and memory. The pathophysiological mechanisms underpinning seizure-induced cognitive impairment are not fully understood, and critical variables such as sex and dynamic brain states with regard to cognitive outcomes have not been explored. We hypothesized that in comparison to control (CTL) rats, ELS rats would exhibit deficits in spatial cognition correlating with impaired dynamic neural signal coordination between the hippocampus and medial prefrontal cortex (mPFC). Methods: Male and female rat pups were given 50 flurothyl-induced seizures over 10 days starting at postnatal Day 15. As adults, spatial cognition was tested through active avoidance on a rotating arena. Microwire tetrodes were implanted in the mPFC and CA1 subfield. Single cells and local field potentials were recorded and analyzed in each region during active avoidance and sleep. Results: ELS males exhibited avoidance impairments, whereas female rats were unaffected. During avoidance, hippocampus-mPFC coherence was higher in CTL females than CTL males across bandwidths. In comparison to CTL males, ELS male learners exhibit increased coherence within theta bandwidth as well as altered bursttiming in mPFC cell activity. Hippocampus-mPFC coherence levels are predictive of cognitive outcome in the active avoidance spatial task. Significance: Spatial cognitive outcome post-ELS is sex-dependent, as females fare better than males. ELS males that learn the task exhibit increased mPFC coherence levels at low-theta frequency, which may compensate for ELS effects on mPFC cell timing. These results suggest that coherence may serve as a biomarker for spatial cognitive outcome post-ELS and emphasize the significance of analyzing sex and dynamic cognition as variables in understanding seizure effects on the developing brain.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Moreover, ELS cognitive outcome variables such as dynamic coordination efficacy in the hippocampus-mPFC circuit and sex [28][29][30] have not been studied.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of early life seizures on coordination of hippocampal–prefrontal networks: Influence of sex and dynamic brain states

et al. 2021

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“…There are well-established sex differences in psychiatric comorbidities associated with epilepsy [ 157 ]. For example, gender difference in depressive symptoms were reported, with female epilepsy patients being more affected [ 158 ].…”

Section: Epilepsy and Depressionmentioning

confidence: 99%

Impact of Stress on Epilepsy: Focus on Neuroinflammation—A Mini Review

Espinosa‐García

Zeleke

Rojas

2021

IJMS

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Epilepsy, one of the most common neurological disorders worldwide, is characterized by recurrent seizures and subsequent brain damage. Despite strong evidence supporting a deleterious impact on seizure occurrence and outcome severity, stress is an overlooked component in people with epilepsy. With regard to stressor duration and timing, acute stress can be protective in epileptogenesis, while chronic stress often promotes seizure occurrence in epilepsy patients. Preclinical research suggests that chronic stress promotes neuroinflammation and leads to a depressive state. Depression is the most common psychiatric comorbidity in people with epilepsy, resulting in a poor quality of life. Here, we summarize studies investigating acute and chronic stress as a seizure trigger and an important factor that worsens epilepsy outcomes and psychiatric comorbidities. Mechanistic insight into the impact of stress on epilepsy may create a window of opportunity for future interventions targeting neuroinflammation-related disorders.

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Multi‐omic strategies applied to the study of pharmacoresistance in mesial temporal lobe epilepsy

et al. 2021

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Sex Differences in the Epilepsies and Associated Comorbidities: Implications for Use and Development of Pharmacotherapies

Abstract: Christian et al.

Cited by 75 publications

References 508 publications

Effects of early life seizures on coordination of hippocampal–prefrontal networks: Influence of sex and dynamic brain states

Effects of early life seizures on coordination of hippocampal–prefrontal networks: Influence of sex and dynamic brain states

Impact of Stress on Epilepsy: Focus on Neuroinflammation—A Mini Review

Multi‐omic strategies applied to the study of pharmacoresistance in mesial temporal lobe epilepsy

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