The expression of astroglial glutamate transporters in patients with focal cortical dysplasia: an immunohistochemical study.
OBJECTIVE
An abnormal increase in the extracellular glutamate is thought to play a crucial role in the initiation, spread, and maintenance of seizure activity.In normal conditions, the majority of this excess glutamate is cleared via glial glutamate transporters (EAAT-1 and EAAT-2). We aimed to examine the immunohistochemical expression of these transporters in the dysplastic tissues of patients with focal cortical dysplasia (FCD).


METHODS
The parafin-embedded dysplastic tissues of 33 patients who were operated on due to medically intractable epilepsy and histopathologically diagnosed with FCD between 2001 and 2006 were stained immunohistochemically with appropriate antibodies, and the distribution and intensity of immunoreactivity (IR) of EAAT-1 and EAAT-2 were examined.The findings were compared with the histologically normal tissues of five patients who underwent temporal lobectomy for epilepsy surgery and 10 fresh postmortem cases.


RESULTS
In the majority of the patients, the EAAT-1 and EAAT-2 IR were decreased, their astrocytic expression were lower, and the pattern of distribution were more diffused when compared to the control groups.Analyzing these findings according to the types of FCD revealed that as the severity of the dysplasia increased, the IR and astrocytic expression of both transporters are decreased and their distribution tend to be more "diffused."


CONCLUSIONS
The results of this study suggest a relationship between the decreased glutamate transporter expressions in dysplastic tissues which,in turn, may cause increased extracellular concentrations of glutamate and FCD pathophysiology.Further studies with larger patient populations,investigating the expression of glutamate transporters at mRNA and protein levels, are required to clarify their roles in the pathophysiology of FCD.
Ulu
Mustafa Onur
MO
Department of Neurosurgery, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey. dronurulu@gmail.com
Tanriverdi
Taner
T
Oz
Buge
B
Biceroglu
Hüseyin
H
Isler
Cihan
C
Eraslan
Berna Senel
BS
Ozkara
Cigdem
C
Ozyurt
Emin
E
Uzan
Mustafa
M
D000328:Adult; D001253:Astrocytes / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000378:metabolism* / Q000503:physiopathology; D027341:Excitatory Amino Acid Transporter 1 / Q000032:analysis / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000032:analysis / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D054220:Malformations of Cortical Development / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008875:Middle Aged; D050496:Vesicular Glutamate Transport Proteins / Q000378:metabolism*
D015415:Biomarkers; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050496:Vesicular Glutamate Transport Proteins; D018698:Glutamic Acid