Sex-specific consequences of early life seizures
Citation
Akman O, Moshé SL, Galanopoulou AS. Sex-specific consequences of early life seizures. Neurobiology of Disease. 2014; 72(Part B): 153–166. doi:10.1016/j.nbd.2014.05.021Abstract
Seizures are very common in the early periods of life and are often associated with poor neurologic outcome in
humans. Animal studies have provided evidence that early life seizures may disrupt neuronal differentiation
and connectivity, signaling pathways, and the function of various neuronal networks. There is growing
experimental evidence that many signaling pathways, like GABAA receptor signaling, the cellular physiology
and differentiation, or the functional maturation of certain brain regions, including those involved in seizure
control, mature differently in males and females. However, most experimental studies of early life seizures
have not directly investigated the importance of sex on the consequences of early life seizures. The sexual
dimorphismof the developing brain raises the question that early seizures could have distinct effects in immature
females and males that are subjected to seizures.Wewill first discuss the evidence for sex-specific features of the
developing brain that could be involved in modifying the susceptibility and consequences of early life seizures.
We will then review how sex-related biological factors could modify the age-specific consequences of induced
seizures in the immature animals. These include signaling pathways (e.g., GABAA receptors), steroid hormones,
growth factors. Overall, there are very few studies that have specifically addressed seizure outcomes in developing
animals as a function of sex. The available literature indicates that a variety of outcomes (histopathological,
behavioral, molecular, epileptogenesis) may be affected in a sex-, age-, region-specific manner after seizures
during development. Obtaining a better understanding for the gender-related mechanisms underlying
epileptogenesis and seizure comorbidities will be necessary to develop better gender and age appropriate therapies.