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Isolation of Cerebral Capillaries from Fresh Human Brain Tissue
Published on: September 12, 2018
Apolipoprotein E controls ATP-binding cassette transporters in the ischemic brain
1Department of Neurology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, D-45122 Essen, Germany.
Science Signaling
|October 7, 2010
Summary
Apolipoprotein E (ApoE) signaling in ischemic brain capillaries affects drug transporter abundance, hindering brain drug delivery. Inhibiting ApoE signaling may improve therapeutic access to the brain.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Adenosine triphosphate-binding cassette transporters (ABCB1 and ABCC1) are crucial for regulating drug permeability across the blood-brain barrier.
- Ischemic stroke alters the expression and localization of these transporters, limiting the efficacy of brain-targeted therapeutics.
Purpose of the Study:
- To investigate the role of apolipoprotein E (ApoE) in regulating the abundance of ABCB1 and ABCC1 transporters in ischemic cerebral capillaries.
- To explore the potential of targeting ApoE signaling pathways to enhance drug delivery to the ischemic brain.
Main Methods:
- Immunohistochemical analysis of ischemic and contralateral cerebral microvessels to detect apolipoprotein E (ApoE) and ApoE receptor-2 (ApoER2) expression.
- Assessment of c-Jun N-terminal kinase (JNK) activity in response to ApoE signaling.
- Quantification of ABCB1 and ABCC1 transporter abundance in post-ischemic brain tissue.
Main Results:
- Apolipoprotein E (ApoE) was found on ischemic microvessels but not in control tissues.
- ApoE signaling, via ApoE receptor-2 (ApoER2), reduced c-Jun N-terminal kinase (JNK) activity.
- ApoE modulated the post-ischemic abundance of ABCB1 and ABCC1, influencing drug accumulation in the brain.
Conclusions:
- Apolipoprotein E (ApoE) plays a significant role in regulating drug transporter expression in the ischemic brain.
- Inhibiting ApoE signaling presents a potential therapeutic strategy to overcome drug delivery barriers in ischemic stroke.
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