Balloon cells in malformations of cortical development: friends or foes?

Balloon cells (BCs) are specific pathological marker of cortical malformations during brain development, often associated with epilepsy and development delay. Although a large number of studies have investigated the role of BCs in these diseases, the specific function of BCs as either epileptogenic or antiepileptic remains controversial. Therefore, we reviewed literatures on BCs, delved into the molecular mechanisms and signaling pathways, and updated their profile in several aspects. Firstly, BCs are heterogeneous and some of them show progenitor/stem cell characteristics. Secondly, BCs are relatively silent in electrophysiology but not completely isolated from their surroundings. Notably, abnormal mTOR signaling and aberrant immunogenic process have been observed within BCs-containing malformations of cortical development (MCDs). The question whether BCs function as the evildoer or the defender in BCs-containing MCDs is further discussed. Importantly, this review provides perspectives on future investigations of the potential role of BCs in epilepsy.