Abstracts

In the brain, the principal location of the efflux transporter P-glycoprotein (ABCB1) is on the luminal membrane of endothelial cells, which are a major part of the blood-brain barrier (BBB). ABCB1 transports many lipophilic drugs, such as anticonvulsant drugs, back to the blood. Microvessels in the epileptic focus of pharmacoresistant patients with temporal lobe epilepsy (TLE) have been reported to overexpress ABCB1. Also in rodent models of TLE, an upregulation of ABCB1 was found in brain regions, which are important for the development and progression of seizure activity. Hence, the brain-uptake of anticonvulsant drug may be reduced. Expression of ABCB1 after seizures has also been described in astrocytes, whereas it is not clear whether neurons can express ABCB1.
The aim of the present immunohistochemical study was to investigate the expression-pattern of ABCB1 24 h after a status epilepticus induced by the cholinomimetic agonist pilocarpine, a widely used model of TLE.
Surprisingly, besides endothelial ABCB1 staining, neurons in the CA3c/CA4 sectors and hilus of the hippocampus formation showed intense ABCB1 staining. Double immunolabeling and confocal microscopy demonstrated that ABCB1 was colocalized with the neuronal marker NeuN, but not with the astrocyte marker GFAP. In control rats neuronal ABCB1 staining was absent.
Based on recent evidences, ABCB1 may play a role in the cell defense of active cell death. Thus ABCB1 overexpression in hippocampal neurons could be involved in the prevention of neuronal damage developing after seizures such as produced by pilocarpine. Furthermore, an overexpression of ABCB1 in neurons might reduce the uptake of anticonvulsant drugs and consequently might contribute to pharmacoresistance to anticonvulsant drugs that act via intracellular target sites.
[Supported by: A grant from the Deutsche Forschungsgemeinschaft (LO 274/9).]