SPATIAL AND TEMPORAL EXPRESSION OF P-GLYCOPROTEIN IN THE CONGENITALLYHYDROCEPHALIC HTX RAT-BRAIN

The purpose of the present study is to examine spatial and temporal ex pression of P-glycoprotein in the brain of congenitally hydrocephalic HTX rats. P-glycoprotein has been reported not only as a drug efflux p ump but also one of the factors that restricts brain edema. We examine d the rat brain from postnatal day 1 to 60 using light and electron mi croscopy, immunohistochemistry, Western immunoblot and reverse transcr iptase-polymerase chain reaction (RT-PCR) methods with monoclonal anti body specific for P-glycoprotein. Immunohistochemically, the positive anti-P-glycoprotein reactivity was found in capillaries of the normal control rat cerebrum. In the hydrocephalic HTX rat brains, it was also found in the capillaries, but only very weak to no reactivity was fou nd in the capillaries of the spongy changes and cystic wall in the sub cortical and lateral periventricular white matter. Immunoelectron micr oscopically the reaction product was found exclusively on the luminal surface of the capillary endothelium in control rats. A tracer study w ith intracardiac perfusion of lanthanum chloride showed that lanthanum penetrated the tight junctions and passed through the intercellular s pace. In the Western immunoblot analysis, P-glycoprotein of 170 kDa wa s detected clearly in most normal control rat brains but it was not fo und in the hydrocephalic HTX rat brains. Moreover mdr1 P-glycoprotein gene expression in the subcortical white matter was examined by RT-PCR . It was detected in all normal control rat brains, but not found in t he hydrocephalic HTX rat brains. The results suggested that the absenc e of P-glycoprotein expression in the capillaries of deep subcortical and lateral periventricular white matter of hydrocephalic HTX rats led to a deficiency of the blood-brain barrier and might be related to va sogenic enema and to the formation of the spongy changes and cystic ca vities.