MULTI-DRUG RESISTANCE1 (MDR1) PROTEIN EXPRESSION IN RASMUSSEN[apos]S ENCEPHALITIS
Abstract number :
1.093
Submission category :
Year :
2003
Submission ID :
3733
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
David V. Lardizabal, Berit Jacobson, Zhong Ying, William Bingaman, Imad Najm Neurology, Section of Epilepsy, Cleveland Clinic Foundation, Cleveland, OH; Neurosurgery, Section of Epilepsy Surgery, Cleveland Clinic Foundation, Cleveland, OH
The mechanism of epileptogenecity and anti-epileptic drug resistance in Rasmussen[apos]s encephalitis remains unknown. There is growing evidence that the blood brain barrier transporter protein, MDR1, is responsible for the drug efflux of anti-epileptic drugs in most epileptogenic tissues. There are no reported cases of MDR1 expression in Rasmussen[apos]s encephalitis. OBJECTIVE: To demonstrate the relative abundance of Multi-Drug Resistance-1 proteins in epileptic brain tissue resected from patients with Rasmussen[rsquo]s encephalitis.
Immunocytochemistry (ICC) using anti-MDR1 antibody (C494) was used to study MDR1 protein expression in resected epileptic brain tissue from 5 patients with the pathologically proven Rasmussen[rsquo]s encephalitis, one patient with a history of drug-resistant temporal lobe epilepsy secondary to cortical dysplasia, and autopsy tissue from one patient with a previous history of well-controlled epilepsy using carbamazepine monotherapy and normal MRI.
Histopathologically, tissue from 5 Rasmussen[rsquo]s encephalitis patients, aged 2 to 15 years, who had undergone functional hemispherectomy, showed microglial nodules, reactive astrocytosis, and focal brain atrophy. Intense labeling of MDR1 was noted on the endothelium of the capillaries, smaller blood vessels, and reactive astrocytes in tissue from these cases. MDR 1 protein expression in the tissue resected from the patient with temporal lobe cortical dysplasia was less intense that the one seen in the Rasmussen[rsquo]s tissue. There was minimal labeling with MDR1 antibodies in the autopsy tissue from the patient with drug responsive epilepsy.
This study demonstrates the relative abundance of MDR1 proteins in Rasmussen[rsquo]s encephalitis brain tissue. Together with other epileptogenic brain pathologies, enhanced MDR1 expression may be one of the common mechanisms of anti-epileptic drug resistance.
[Supported by: K08- NS02046 and R21- NS42354 grants to IN from the National Institutes of Health (National Institutes of Neurological Disorders and Stroke, NINDS)]