Commentary on Li et al. “Disrupted female estrous cyclicity in the intrahippocampal kainic acid mouse model of temporal lobe epilepsy”

Disruptions of biological rhythms represent an important category of epilepsy comorbidities. The dysfunctions of the biological clock occur on different levels, including circadian (eg, core temperature), infradian (eg, menstrual cycle), and ultradian (eg, sleep structure) domains. As other comorbidities, chronobiological dysregulation is likely to contribute to further deterioration of quality of life (QoL) in people in epilepsy. Yet, the problem has been receiving only scarce attention, especially in laboratory research. Reproductive dysfunction is a common disorder in both women and in men with epilepsy. For example, menstrual disorders are 2-3 times more prevalent in women in epilepsy than in the general population. Understandably, the negative impact of disruptions in the menstrual cycle may have profound detrimental effects on QoL, both psychological (eg, due to infertility), and biological (considering ubiquitous role of sex hormones in regulating many essential physiological functions). Understanding the mechanisms that underlie the disruptions of reproductive cycle is essential for their effective management. In turn, for mechanistic studies the availability of animal models of comorbidity between epilepsy and menstrual cycle disruption is critical. Indeed, only an animal system can afford the examination of biological basis of the comorbidity, by removing psychological factors and off-target effects of antiepileptic interventions. Earlier studies in adult male Sprague-Dawley rats using the self-sustaining limbic status epilepticus (SSLSE) model or hippocampal kindling, showed neuronal loss in certain hypothalamic regions (medial preoptic nucleus, dorsal medial hypothalamus) of rats with post-SSLSE epilepsy but not in kindled animals. Hypothalamic injury at the medial preoptic ventromedial, paraventricular, and ventral pre-mammillary Andrey Mazarati, MD, PhD, is Professor at the Department of Pediatrics, UCLA School of Medicine Dr.Aristea S. Galanopoulou is a Professor of Neurology and Neuroscience at the Albert Einstein College of Medicine