Microvascular P-glycoprotein expression at the blood-brain barrier following focal astrocyte loss and at the fenestrated vasculature of the area postrema.
The multidrug transporter, P-glycoprotein, expressed at the blood-brain barrier is thought to be important for limiting access of toxic agents to the brain, but its relationship to astrocyte expression is unclear. We have studied P-glycoprotein expression in the inferior colliculus after a temporary loss of blood-brain barrier integrity following chemically induced astrocyte loss and at the fenestrated vascular endothelium of the area postrema. Male Fisher F344 rats given 3-chloropropanediol showed astrocyte loss from 12 to 24 h until the lesion was repopulated 8-28 days later. In non-dosed tissue, P-glycoprotein expression was seen the entire length of platelet endothelial cell adhesion molecule immunoreactive vessels. Within 6 h of dosing, a significant (p<0.05) reduction in the total length of P-glycoprotein immunoreactive vasculature was evident. By 48 h, P-glycoprotein immunoreactivity was heavily fragmented. The total length of P-glycoprotein immunoreactive vessels became minimal at 4 days (p<0.001) but was still present in many vessels. From 6 to 28 days, P-glycoprotein immunoreactivity returned across the inferior colliculus, in parallel with astrocytic repopulation of the lesion, and by 28 days resembled that seen in control tissue. The area postrema showed GFAP immunoreactive astrocytes but which made limited contact with the vasculature, while the platelet endothelial cell adhesion molecule immunoreactive vasculature showed no expression of P-glycoprotein. These findings provide evidence supporting a link between GFAP-astrocyte and P-glycoprotein expression in the mature brain vasculature in vivo.
Willis
Colin L
CL
MRC Applied Neuroscience Group, School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham NG7 2UH, UK. cwillis@email.arizona.edu
Taylor
Gemma L
GL
Ray
David E
DE
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D031608:Area Postrema / Q000033:anatomy & histology / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D001812:Blood-Brain Barrier / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002629:Chemosterilants / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000293:injuries / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D000517:alpha-Chlorohydrin / Q000494:pharmacology