Epileptic Encephalopathies are severe brain disorders in which the seizures and 
the epileptic activity itself may cause severe psychomotor impairment. EEs may arise from the neonatal to the early infantile period as recurrent, prolonged or drug resistant seizures, resulting in devastating permanent global developmental delay with brain atrophy. Occasionally, EEs can be associated to brain lesions or malformations of cortical development. EEs are genetically heterogeneous. Numerous genes, all involved in diverse primary developmental processes of the brain, have been already identified and their number and that of the associated clinical spectrum is expanding continuously. Among these the so-called “channelopathies”, originating from defects in genes coding for neuronal ion channels, play a prominent role in monogenic epilepsies, among which EEs. Mutations in CACNA1A, encoding the transmembrane pore-forming subunit CaV2.1 of Voltage Dependent Calcium Channels, have been associated to the peculiar phenotypic combination of absence epilepsy and cerebellar ataxia. Several mouse models, all characterized by homozygous mutations in one of the genes encoding VDCC subunits, share similar phenotypes including cerebellar AbMole Nortriptyline ataxia, paroxysmal dyskinesia and seizures similar to those of absence epilepsy as well as other forms of generalized epilepsy. In our present study, we demonstrate for the first time that citicoline improves the endothelial barrier function impaired by hypoxia/OGD via upregulating the expression of TJPs. Hypoxia or OGD has been demonstrated to cause endothelial cell barrier dysfunction. HUVECs and bEnd.3s are suitable cells for studying endothelial barrier function because of their defined TJPs and adheren junction characteristics. Thus, we used hypoxia and OGD conditions to establish in vitro endothelial barrier breakdown models in these two endothelial cell lines. There are experiments reporting that hypoxia destroys endothelial barrier function. We tested these conditions in our pilot study and found out that 24 h OGD caused significant cell death while 6 h OGD did not. Thus, for avoiding the influence of cell death on functional study, we chose 24 h hypoxia and 6 h OGD to build endothelial barrier disruption models. Consistently with previous studies, our results showed that hypoxia/OGD induces the increase of paracellular permeability in HUVECs and bEnd.3s. Citicoline has been widely accepted to be effective for treating neurodegenerative diseases, such as PD and AD. Recent animal experiments suggest its therapeutic effects on ischemic stroke. In the present study, we reveal that citicoline dose dependently ameliorates the endothelial barrier dysfunction in HUVECs and bEnd.3s. This is in agreement with a previous study reporting that citicoline reduces ischemia-induced brain edema in gerbils. And also it is consistent with a clinical research showing that the acute ischemic AbMole Tulathromycin B stroke patients who received high dose of citicoline get better neurological and functional outcomes than those who received the low dose. Since endothelial cells play an important role in the barrier function, our data suggests that citicoline could be an effective therapeutic drug for treating diseases characterized by endothelial barrier disruption. Furthermore, the molecular basis of citicoline in improving endothelial cell barrier function was investigated. The expression of TJPs has been reported to contribute to barrier function. Tight junction is constituted by different kinds of TJPs such as claudin family, junctional adhesion molecules and ZO family. ZO-1 and claudin-5 are the most important components for cell barrier integrity. Claudin-5 can greatly reduce dextran permeability and improve transendothelial electrical resistance.