Abstracts

Rationale: Rasmussen encephalitis (RE) is a rare neurological disorder of childhood characterized by unilateral inflammation of cerebral cortex, progressive neurological and cognitive deterioration, and pharmacoresistant focal epilepsy. The pathogenesis of hemispheric atrophy, focal epilepsy (epilepsia partialis continua) without converting into generalized epilepsy is still enigmatic. Activation of adenosine A1 receptor has been proved to prevent the spatial spread of seizures. Adenosine dysfunction as an early component of the epileptogenic cascade and associated with the focal origin of seizure activity, plays an important role in focal seizures of RE. We hypothesized that the epileptogenic mechanisms underlying RE is related to changes in neuronal adenosine A1 receptor (A1R) expression and that those changes might be associated with the clinical and electrographic characteristics of focal seizures in these patients Methods: Immunnohistochemistry approach was used to examine the expression of A1R and adenosine kinase (ADK) in surgically resected human epileptic cortical specimens from RE (n=12), and compared that with control cortical tissue. The quantification of A1R and ADK expression in RE versus controls was evaluated with western blot. Results: A1R was predominantly expressed in perinuclear (cytoplasmic) of neurons but lack of expression in reactive astrocytes and microglias. Upregulation of neuronal A1R was observed in the lesions of RE. Reactive astrocytes and subpopulation of remnant neurons demonstrated over-expression of the ADK within the lesions of RE. Significant Increasing of A1R and ADK expression in RE compared with control was proved by western blot. Conclusions: These results suggest that over-expression of ADK is a common pathologic hallmark of RE, upregulation of neuronal A1R in human Rasmussen's encephalitis is crucial in keeping epileptic foci localized. A1R is a target in the treatment of epilepsy associated with RE. Funding: This Project was supported by the Grant from the BIBD-PXM2013_014226_07_000084, National Natural Science Foundation of China (81571275), Scientific Research Common Program of Beijing Commission of Education (KM201410025027), Beijing Municipal Natural Science Foundation (7144217) and Beijing Municipal Science & Technology Commission (Z131107002213171). We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.