Author ORCID Identifier
Date Available
4-27-2018
Year of Publication
2018
Degree Name
Master of Science (MS)
Document Type
Master's Thesis
College
Pharmacy
Department/School/Program
Pharmaceutical Sciences
First Advisor
Dr. Björn Bauer
Abstract
Epilepsy affects 3.4 million patients in the USA and is characterized by recurring seizures. The blood-brain barrier is leaky in epilepsy and may contribute to seizure progression but the mechanisms which cause this leakage are not fully understood. We hypothesized that seizures trigger LOX- and COX-mediated blood-brain barrier leakage and that dual LOX/COX inhibition prevents barrier leakage in vivo. To test this hypothesis, we administered either the dual LOX/COX inhibitor licofelone or a combination of the 5-LOX inhibitor zileuton and the COX-2 inhibitor celecoxib to rats that experienced status epilepticus (SE). Serum and brain capillaries were isolated 48 hours after SE and serum S100β levels were measured and Texas Red™ leakage rates were determined. Dual inhibition of 5-LOX and COX prevented serum S100β elevations observed in SE rats in a dose-dependent manner with licofelone. Inhibition of 5-LOX and COX-2 with zileuton and celecoxib completely prevented serum S100β elevation. Texas Red™ leakage rates for SE rats were also reduced in a dose-depended manner with licofelone and reduced to control rates with zileuton and celecoxib. These data support our hypothesis that seizure-induced blood-brain barrier leakage is mediated by LOX and COX, and inhibition of these enzymes prevents barrier leakage.
Digital Object Identifier (DOI)
https://doi.org/10.13023/ETD.2018.159
Recommended Citation
Sokola, Brent S., "DUAL LOX/COX INHIBITION: A NOVEL STRATEGY TO PREVENT NEUROVASCULAR LEAKAGE IN EPILEPSY" (2018). Theses and Dissertations--Pharmacy. 83.
https://uknowledge.uky.edu/pharmacy_etds/83
