title: Upregulation of adenosine kinase in Rasmussen encephalitis.
abstract: Rasmussen encephalitis (RE) is a rare neurologic disorder of childhood characterized by unihemispheric inflammation, progressive neurologic deficits, and intractable focal epilepsy. The pathogenesis of RE is still enigmatic. Adenosine is a key endogenous signaling molecule with anticonvulsive and anti-inflammatory effects, and our previous work demonstrated that dysfunction of the adenosine kinase (ADK)-adenosine system and astrogliosis are the hallmarks of epilepsy. We hypothesized that the epileptogenic mechanisms underlying RE are related to changes in ADK expression and that those changes might be associated with the development of epilepsy in RE patients. Immunohistochemistry was used to examine the expression of ADK and glial fibrillary acidic protein in surgically resected human epileptic cortical specimens from RE patients (n = 12) and compared with control cortical tissues (n = 6). Adenosine kinase expression using Western blot and enzymatic activity for ADK were assessed in RE versus control samples. Focal astrogliosis and marked expression of ADK were observed in the lesions of RE. Significantly greater ADK expression in RE versus controls was demonstrated by Western blot, and greater enzymatic activity for ADK was demonstrated using an enzyme-coupled bioluminescent assay. These results suggest that upregulation of ADK is a common pathologic hallmark of RE and that ADK might be a target in the treatment of epilepsy associated with RE.
authors.affiliation: From the Department of Neurosurgery (GL, YG, FZ, JZ, CL), Brain Institute (QG, YC, TL), and Department of Neurology (TL), Epilepsy Center, and Department of Neuropathology (KY, XQ), Beijing Sanbo Brain Hospital, Capital Medical University, Beijing, China.
authors.forename: Guoming
authors.initials: G
authors.lastname: Luan
authors.forename: Qing
authors.initials: Q
authors.lastname: Gao
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Guan
authors.forename: Feng
authors.initials: F
authors.lastname: Zhai
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Changqing
authors.initials: C
authors.lastname: Liu
authors.forename: Yin
authors.initials: Y
authors.lastname: Chen
authors.forename: Kun
authors.initials: K
authors.lastname: Yao
authors.forename: Xueling
authors.initials: X
authors.lastname: Qi
authors.forename: Tianfu
authors.initials: T
authors.lastname: Li
mesh_terms: D000248:Adenosine Kinase / Q000378:metabolism*; D000293:Adolescent; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000201:enzymology* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004660:Encephalitis / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D005260:Female; D005911:Gliosis / Q000150:complications / Q000201:enzymology / Q000473:pathology; D006801:Humans; D008297:Male; D015854:Up-Regulation
chemical_list: D000248:Adenosine Kinase