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Upregulation of adenosine kinase in Rasmussen encephalitis.

Luan G, Gao Q, Guan Y, Zhai F, Zhou J, Liu C, Chen Y, Yao K, Qi X, Li T - J. Neuropathol. Exp. Neurol. (2013)

Bottom Line: 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).Focal astrogliosis and marked expression of ADK were observed in the lesions of RE.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.

View Article: PubMed Central - PubMed

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.

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.

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Adenosine kinase (ADK) immunoreactivity in bandlike subpial gliosis (Chaslin gliosis). (A–C) Chaslin gliosis in the cortical gray matter ([A] arrow, H&E stain), GFAP immunoreactivity ([B] arrow) and ADK immunoreactivity ([C] arrow) in the astroglial component within the bandlike subpial gliosis. Scale bar = 25 μm.
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Figure 3: Adenosine kinase (ADK) immunoreactivity in bandlike subpial gliosis (Chaslin gliosis). (A–C) Chaslin gliosis in the cortical gray matter ([A] arrow, H&E stain), GFAP immunoreactivity ([B] arrow) and ADK immunoreactivity ([C] arrow) in the astroglial component within the bandlike subpial gliosis. Scale bar = 25 μm.

Mentions: In RE specimens, neuronal loss was observed in the lesion area (Fig. 2A1, A2, A3). Occasional foci of neuronophagia (Fig. 2A2) and marked perivascular cell loss (Fig. 2A3) were seen. There were GFAP-positive reactive astrocytes within lesions (Fig. 2B1, B2, B3) and marked reactive astrogliosis in perivascular areas (Fig. 2B3), as well as bandlike subpial gliosis (Chaslin gliosis) (Fig. 3A, B). Concomitant with reactive astrogliosis, ADK immunoreactivity was observed in cells with typical astroglial morphology (Fig. 2C1, C2, C3) within lesions; they were prominent in perivascular areas (Fig. 2C3) and in areas with bandlike subpial gliosis region (Fig. 3C); ADK was remarkably observed in the astroglial component, with a predominant cytoplasmic localization (Figs. 2C2, C3; 3C). Double labeling confirmed ADK expression in GFAP-positive reactive astrocytes within lesions (Fig. 4A4, B4, C4, D4) and perivascular areas (Fig. 4A1, B1, C1, D1, A2, B2, C2, D2, A3, B3, C3, D3).


Upregulation of adenosine kinase in Rasmussen encephalitis.

Luan G, Gao Q, Guan Y, Zhai F, Zhou J, Liu C, Chen Y, Yao K, Qi X, Li T - J. Neuropathol. Exp. Neurol. (2013)

Adenosine kinase (ADK) immunoreactivity in bandlike subpial gliosis (Chaslin gliosis). (A–C) Chaslin gliosis in the cortical gray matter ([A] arrow, H&E stain), GFAP immunoreactivity ([B] arrow) and ADK immunoreactivity ([C] arrow) in the astroglial component within the bandlike subpial gliosis. Scale bar = 25 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3815008&req=5

Figure 3: Adenosine kinase (ADK) immunoreactivity in bandlike subpial gliosis (Chaslin gliosis). (A–C) Chaslin gliosis in the cortical gray matter ([A] arrow, H&E stain), GFAP immunoreactivity ([B] arrow) and ADK immunoreactivity ([C] arrow) in the astroglial component within the bandlike subpial gliosis. Scale bar = 25 μm.
Mentions: In RE specimens, neuronal loss was observed in the lesion area (Fig. 2A1, A2, A3). Occasional foci of neuronophagia (Fig. 2A2) and marked perivascular cell loss (Fig. 2A3) were seen. There were GFAP-positive reactive astrocytes within lesions (Fig. 2B1, B2, B3) and marked reactive astrogliosis in perivascular areas (Fig. 2B3), as well as bandlike subpial gliosis (Chaslin gliosis) (Fig. 3A, B). Concomitant with reactive astrogliosis, ADK immunoreactivity was observed in cells with typical astroglial morphology (Fig. 2C1, C2, C3) within lesions; they were prominent in perivascular areas (Fig. 2C3) and in areas with bandlike subpial gliosis region (Fig. 3C); ADK was remarkably observed in the astroglial component, with a predominant cytoplasmic localization (Figs. 2C2, C3; 3C). Double labeling confirmed ADK expression in GFAP-positive reactive astrocytes within lesions (Fig. 4A4, B4, C4, D4) and perivascular areas (Fig. 4A1, B1, C1, D1, A2, B2, C2, D2, A3, B3, C3, D3).

Bottom Line: 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).Focal astrogliosis and marked expression of ADK were observed in the lesions of RE.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.

View Article: PubMed Central - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus