The protective effect of carbenoxolone on gap junction damage in the hippocampal CA1 area of a temporal lobe epilepsy rat model

Yi Shu, Can Zhu, Min Zeng, Qiong Zhan, Zhiping Hu, Xiaomei Wu


Background: Astrocytes are one of the most important types of neural cells in the central nervous system (CNS). Dysfunctional gap junction (GJ) communication could play an underlying role in epileptogenesis. Carbenoxolone (CBX) is a conventional chemical GJ blocker, and its target is connexin 43 (Cx43). Previous studies have shown that CBX can inhibit status epilepticus (SE) and spontaneous epileptic seizures (SESs). However, there is little information about the direct interaction between CBX and Cxs in temporal lobe epilepsy (TLE).
Methods: The behavior of epileptic rats was observed. Moreover, micromorphological changes in the hippocampal cornu ammonis 1 (CA1) area of epileptic rats following CBX injection were determined through transmission electron microscopy (TEM). To illustrate the possible mechanism of these changes, the Western blot method was used.
Results: After the injection of CBX, the seizure frequency, seizure duration, latency period to the first instance of SES, SESs behavioral score according to a scoring system developed by Velíšková and microstructures in the CA1 area were shown to be improved 60 days after SE by TEM. Furthermore, the dynamic expression patterns of Cx43 and Cx43 phosphorylated at Ser368 continuously declined after the injection of CBX until 60 days after SE.
Conclusions: CBX may contribute to the improvement of GJ dysfunction during epileptogenesis in the hippocampal CA1 area in a TLE rat model.