Akman Ozlem, Moshé Solomon L, Galanopoulou Aristea S
Department of Physiology, Faculty of Medicine, Istanbul Bilim University, 34394 Istanbul, Turkey.
Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy, Montefiore Epilepsy Management Center, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, 10461, USA; Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, 10461, USA; Department of Pediatrics, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, 10461, USA.
Neurobiol Dis. 2014 Dec;72 Pt B(Pt B):153-66. doi: 10.1016/j.nbd.2014.05.021. Epub 2014 May 27.
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 dimorphism of the developing brain raises the question that early seizures could have distinct effects in immature females and males that are subjected to seizures. We will 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.
癫痫发作在生命早期非常常见，并且在人类中常常与不良的神经学预后相关。动物研究已经提供了证据，表明生命早期的癫痫发作可能会扰乱神经元分化和连接、信号通路以及各种神经网络的功能。越来越多的实验证据表明，许多信号通路，如GABAA受体信号通路、细胞生理学和分化，或者某些脑区（包括参与癫痫控制的脑区）的功能成熟，在雄性和雌性中成熟方式不同。然而，大多数关于生命早期癫痫发作的实验研究并没有直接探究性别对生命早期癫痫发作后果的重要性。发育中大脑的性别二态性引发了一个问题，即早期癫痫发作可能对遭受癫痫发作的未成熟雌性和雄性产生不同的影响。我们将首先讨论发育中大脑可能参与改变生命早期癫痫发作易感性和后果的性别特异性特征的证据。然后，我们将回顾与性别相关的生物学因素如何改变未成熟动物中诱导癫痫发作的年龄特异性后果。这些因素包括信号通路（如GABAA受体）、类固醇激素、生长因子。总体而言，很少有研究专门探讨发育中动物癫痫发作结果与性别的关系。现有文献表明，发育期间癫痫发作后，各种结果（组织病理学、行为学、分子学、癫痫发生）可能会以性别、年龄、区域特异性的方式受到影响。为了开发更好的适合性别和年龄的治疗方法，有必要更好地理解癫痫发生和癫痫共病的性别相关机制。
