Abstracts

Rationale: Rasmussen encephalitis (RE) is a rare neurological disorder of childhood characterized by uni-hemispheric inflammation, progressive neurological deficits and intractable focal epilepsy. The pathogenesis of this severely disabling inflammatory disease and associated epilepsy is still enigmatic. Adenosine is a key endogenous signaling molecule with anticonvulsive as well as anti-inflammatory effects, and our previous work demonstrated that dysfunction of adenosine kinase (ADK)-adenosine system and astrogliosis as a hallmark of epilepsy. We hypothesized that the epileptogenic mechanisms underlying RE is related to changes in ADK expression and that those changes might be associated with the development of epilepsy in these patients. Methods: Surgically resected human epileptic cortical specimens from RE (n=12), we use immunohistochemistry approach to examine the expression of ADK and GFAP, double-label immunohistochemistry for coexpression of ADK and GFAP, and compared with control cortical issue. The quantification of ADK expression and enzymatic activity for ADK in RE versus controls was evaluated.Results: Immunocytochemistry experiments show that lymphocytic infiltrates, microglial nodules, neuronal loss, and astrogliosis of the affected hemisphere. Focal astrogliosis and over-expression of the adenosine-metabolizing enzyme ADK was observed in the lesions of RE, especially remarkable within the perivascular area. Significant Increasing of ADK expression in RE compared with control was proved by western blot.Conclusions: These results suggest that dysfunction of ADK-adenosine system and astrogliosis is a common pathologic hallmark of RE. ADK is a potential therapeutic target in the treatment of epilepsy associated with RE.