Effects of a Surgery-induced Peripheral Inflammatory Response on the Blood Brain Barrier

Summary

The purpose for this study is to determine if surgery (repair of descending thoracic aneurysm) causes a temporary decrease in the Blood Brain Barrier's ability to remove drugs from the brain back into the blood. The Blood Brain Barrier surrounds the brain and the spinal cord. This Blood Brain Barrier acts as a filter and allows some things to cross into the brain and allows other matter to be removed. Studies have shown the Blood Brain Barrier is affected by inflammation. Functions of the Blood Brain Barrier in animals have been studied. Human studies with multiple causes of inflammation (e.g. Alzheimer's, Epilepsy, trauma and severe infections in critically Hypothesis: Surgically-induced inflammation will temporarily reduce blood-brain barrier drug efflux transporter function in proportion to the degree of inflammation. The investigators anticipate that inflammation-mediated reductions in drug transporter function will be reflected by an increased cerebral spinal fluid (CSF) concentration of morphine (a PGP substrate) and M3G and M6G (MRP1 substrates). The corresponding in vitro studies will allow us to elucidate the mechanism(s) by which inflammation alters blood brain barrier efflux transport of morphine, M3G and M6G.

Timeline

Start

2009-05

Primary completion

2013-02

Completion

2013-02

Publications

• Background Roberts DJ, Goralski KB. A critical overview of the influence of inflammation and infection on P-glycoprotein expression and activity in the brain. Expert Opin Drug Metab Toxicol. 2008 Oct;4(10):1245-64. doi: 10.1517/17425255.4.10.1245.
• Roberts DJ, Hall RI, Wang Y, Julien LC, Wood J, Goralski KB. S100B as a biomarker of blood-brain barrier disruption after thoracoabdominal aortic aneurysm repair: a secondary analysis from a prospective cohort study. Can J Anaesth. 2021 Dec;68(12):1756-1768. doi: 10.1007/s12630-021-02110-2. Epub 2021 Sep 27.
• Wang Y, Goralski KB, Roberts DJ, Landry K, Issa ME, Sleno L, Julien LC, Wood J, Hall RI. An observational study examining the effects of a surgically induced inflammatory response on the distribution of morphine and its metabolites into cerebrospinal fluid. Can J Anaesth. 2017 Oct;64(10):1009-1022. doi: 10.1007/s12630-017-0933-x. Epub 2017 Jul 14.

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