Glutamate clearance mechanisms in resected cortical dysplasia

Laboratory investigation

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  • 1 Epilepsy Center and
  • 2 Department of Surgical Pathology, Cleveland Clinic, Cleveland, Ohio
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Object

Changes in the expression of glutamate transporters (GLTs) may play a role in the expression of epileptogenicity. Previous studies have shown an increased number of neuronal GLTs in human dysplastic neurons. The expression of glial and neuronal GLTs and glutamine synthetase (GS) in balloon cells (BCs) and BC-containing cortical dysplasia has not been studied.

Methods

The authors analyzed neocortical samples that were resected in 5 patients who had cortical dysplasia–induced medically intractable focal epilepsy and who underwent extraoperative prolonged electrocorticographic (ECoG) recordings. The expressions of glial (GLT1/EAAT2) and neuronal (EAAT3, EAAC1) GLTs and GS proteins were immunohistochemically studied in all 5 resected samples. The authors also assessed in situ colocalization of GLTs and GS with neuronal and glial markers.

Results

Balloon cell–containing cortical dysplasia lesions did not exhibit ictal patterns on prolonged extraoperative ECoG recordings. There was a differential expression of glial and neuronal GLTs in BCs and dysplastic neurons: the majority of BCs highly expressed glial but not neuronal GLTs. Dysplastic neurons showed increased immunohistochemical staining with neuronal EAAT3 but not with EAAT2/GLT1. Moreover, only glial fibrillary acidic protein–positive BCs also expressed GS.

Conclusions

There is a differential GLT expression in dysplastic and balloon cells. The presence of glial GLTs and GS in balloon cell cortical dysplasia suggests a possible antiepileptic role for BCs and is consistent with the reported increased epileptogenicity in GLT1-deficient animals.

Abbreviations used in this paper: BC = balloon cell; ECoG = electrocorticographic; EEG = electroencephalography; FCD = focal cortical dysplasia; GFAP = glial fibrillary acidic protein; GLT = glutamate transporter; GS = glutamine synthetase; NeuN = neuronal nuclei; TBS = Tris-buffered saline.

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Contributor Notes

Address correspondence to: Jorge A. Gonzalez-Martinez, M.D., Ph.D., Epilepsy Center, Cleveland Clinic, 9500 Euclid Avenue, S51, Cleveland, Ohio 44195. email: gonzalj1@ccf.org.

Please include this information when citing this paper: published online November 12, 2010; DOI: 10.3171/2010.10.JNS10715.

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