Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Sci. Signal., 5 October 2010
Vol. 3, Issue 142, p. ra72
[DOI: 10.1126/scisignal.2001213]

RESEARCH ARTICLES

Editor's Summary

Getting Drugs into the Brain and Keeping Them There
Delivery of potentially therapeutic drugs to the brain after a stroke is impeded by changes in the abundance of two transporters found on endothelial cells in brain capillaries. The abundance of ABCB1, which is found on the luminal side of cerebral capillaries and transports drugs from brain to blood, increases with ischemia. In contrast, the abundance of ABCC1, which is found on the abluminal ("brain") side of cerebral capillaries and transports drugs from blood to brain, decreases. ElAli and Hermann showed that these changes in transporter abundance depended on apolipoprotein E (ApoE) signaling through its receptor ApoE receptor–2 (ApoER2). They found ApoE associated with ischemic brain capillaries but not nonischemic capillaries. Moreover, they showed that ApoER2 was preferentially localized to the abluminal surface of brain capillary endothelial cells, which suggests that it might act as a sensor for brain ischemia. The discovery that ApoE signaling through ApoER2 regulates the abundance of ABCB1 and ABCC1 suggests that inhibition of this pathway could enable the enhanced delivery of neuroprotective drugs to the brain after ischemic stroke.

Citation: A. ElAli, D. M. Hermann, Apolipoprotein E Controls ATP-Binding Cassette Transporters in the Ischemic Brain. Sci. Signal. 3, ra72 (2010).

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Targeting blood-brain barrier sphingolipid signaling reduces basal P-glycoprotein activity and improves drug delivery to the brain.
R. E. Cannon, J. C. Peart, B. T. Hawkins, C. R. Campos, and D. S. Miller (2012)
PNAS 109, 15930-15935
   Abstract »    Full Text »    PDF »
The Abluminal Endothelial Membrane in Neurovascular Remodeling in Health and Disease.
D. M. Hermann and A. ElAli (2012)
Science Signaling 5, re4
   Abstract »    Full Text »    PDF »
Apolipoprotein-E Controls Adenosine Triphosphate-Binding Cassette Transporters ABCB1 and ABCC1 on Cerebral Microvessels After Methamphetamine Intoxication.
A. ElAli, A. Urrutia, A. Rubio-Araiz, M. Hernandez-Jimenez, M. I. Colado, T. R. Doeppner, and D. M. Hermann (2012)
Stroke 43, 1647-1653
   Abstract »    Full Text »    PDF »
Increased Blood-Brain Barrier Permeability and Brain Edema After Focal Cerebral Ischemia Induced by Hyperlipidemia: Role of Lipid Peroxidation and Calpain-1/2, Matrix Metalloproteinase-2/9, and RhoA Overactivation.
A. ElAli, T. R. Doeppner, A. Zechariah, and D. M. Hermann (2011)
Stroke 42, 3238-3244
   Abstract »    Full Text »    PDF »
ATP-Binding Cassette Transporters and Their Roles in Protecting the Brain.
A. ElAli and D. M. Hermann (2011)
Neuroscientist 17, 423-436
   Abstract »    PDF »
Science Signaling Podcast: 5 October 2010.
D. M. Hermann and A. M. VanHook (2010)
Science Signaling 3, pc18
   Abstract »    Full Text »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882