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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, GFAP, and NeuN immunostaining in brain tissue of patients with RE. (A1–A3) NeuN staining demonstrates neuron loss in the lesion cortex (A1), occasional foci of neuronophagia (arrows [A2]), and marked cell loss in the perivascular area (arrows [A3]). (B1–B3) GFAP-positive reactive astrocytes within the lesion area (B1, B2) and marked reactive astrogliosis in the perivascular area (arrows [B3]). (C1–C3) Concomitant with reactive astrogliosis, there is cytoplasmic localization of ADK immunoreactivity in cells with typical astroglial morphology within the lesion (C1, C2) and prominent in the perivascular area (arrows [C3]). (D1–D3) There is weak immunostaining for ADK in control cortical gray matter (D1, D2) and sparse glial cells in control white matter (D3). Scale bars = (A1–D1) 100 μm; (A2–D3) 25 μm.
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Figure 2: Adenosine kinase, GFAP, and NeuN immunostaining in brain tissue of patients with RE. (A1–A3) NeuN staining demonstrates neuron loss in the lesion cortex (A1), occasional foci of neuronophagia (arrows [A2]), and marked cell loss in the perivascular area (arrows [A3]). (B1–B3) GFAP-positive reactive astrocytes within the lesion area (B1, B2) and marked reactive astrogliosis in the perivascular area (arrows [B3]). (C1–C3) Concomitant with reactive astrogliosis, there is cytoplasmic localization of ADK immunoreactivity in cells with typical astroglial morphology within the lesion (C1, C2) and prominent in the perivascular area (arrows [C3]). (D1–D3) There is weak immunostaining for ADK in control cortical gray matter (D1, D2) and sparse glial cells in control white matter (D3). Scale bars = (A1–D1) 100 μm; (A2–D3) 25 μm.

Mentions: In control (autopsy) white matter, ADK immunoreactivity was present in sparse glial cells with only weak staining (Fig. 2D3); control cortical gray matter also displayed weak astroglial staining (Fig. 2D1, D2).


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, GFAP, and NeuN immunostaining in brain tissue of patients with RE. (A1–A3) NeuN staining demonstrates neuron loss in the lesion cortex (A1), occasional foci of neuronophagia (arrows [A2]), and marked cell loss in the perivascular area (arrows [A3]). (B1–B3) GFAP-positive reactive astrocytes within the lesion area (B1, B2) and marked reactive astrogliosis in the perivascular area (arrows [B3]). (C1–C3) Concomitant with reactive astrogliosis, there is cytoplasmic localization of ADK immunoreactivity in cells with typical astroglial morphology within the lesion (C1, C2) and prominent in the perivascular area (arrows [C3]). (D1–D3) There is weak immunostaining for ADK in control cortical gray matter (D1, D2) and sparse glial cells in control white matter (D3). Scale bars = (A1–D1) 100 μm; (A2–D3) 25 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Adenosine kinase, GFAP, and NeuN immunostaining in brain tissue of patients with RE. (A1–A3) NeuN staining demonstrates neuron loss in the lesion cortex (A1), occasional foci of neuronophagia (arrows [A2]), and marked cell loss in the perivascular area (arrows [A3]). (B1–B3) GFAP-positive reactive astrocytes within the lesion area (B1, B2) and marked reactive astrogliosis in the perivascular area (arrows [B3]). (C1–C3) Concomitant with reactive astrogliosis, there is cytoplasmic localization of ADK immunoreactivity in cells with typical astroglial morphology within the lesion (C1, C2) and prominent in the perivascular area (arrows [C3]). (D1–D3) There is weak immunostaining for ADK in control cortical gray matter (D1, D2) and sparse glial cells in control white matter (D3). Scale bars = (A1–D1) 100 μm; (A2–D3) 25 μm.
Mentions: In control (autopsy) white matter, ADK immunoreactivity was present in sparse glial cells with only weak staining (Fig. 2D3); control cortical gray matter also displayed weak astroglial staining (Fig. 2D1, D2).

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