Citation

Willyerd FA, Empey P, Philbrick A, Ikonomovic M, Puccio AM, Kochanek PM, Okonkwo DO, Clark R. J. Neurotrauma 2015; 33(2): 226-231.

Affiliation

Phoenix, United States ; fwillyerd@phoenixchildrens.com.

Copyright

(Copyright © 2015, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2015.3879

PMID

25891836

Abstract

ATP-binding cassette (ABC) transport proteins ABCC1 and ABCB1 (also known as multidrug resistance-associated protein 1 and p-glycoprotein, respectively), are key membrane efflux transporters of drugs and endogenous substrates including in the brain. The impact of traumatic brain injury (TBI) on ABCC1 and ABCB1 expression in humans is unknown. We hypothesized that ABCC1 and ABCB1 expression would be altered in brain tissue from patients acutely after severe TBI. Archived TBI samples (n=10) from our Brain Trauma Research Center and control samples (n=7) from our Alzheimer's Disease Research Center were obtained under Institutional Review Board approval. Protein was extracted from fresh frozen cortical brain tissue for western blot analysis and sections were obtained from fixed cortical tissue for immunohistochemistry. Relative abundance of ABCC1 was increased in samples from TBI vs. controls (2.8±2.5 fold; P=0.005). ABCC1 immunohistochemistry was consistent with western blot data, with increased immunoreactivity in cerebral blood vessel walls, as well as cells with the morphological appearance of neurons and glia in TBI vs. CONTROLS: Relative abundance of ABCB1 was similar between TBI and controls (P=0.76), and ABCB1 immunoreactivity was primarily associated with cerebral blood vessels in both groups. These human data show that TBI increases ABCC1 expression in brain, consistent with possible implications for both patients receiving pharmacologic inhibitors and/or substrates of ABCC1 after TBI.

Language: en