Archived
This content is available here strictly for research, reference, and/or recordkeeping and as such it may not be fully accessible. If you work or study at University of Kentucky and would like to request an accessible version, please use the SensusAccess Document Converter.
Author ORCID Identifier
Date Available
4-27-2018
Year of Publication
2018
Document Type
Master's Thesis
Degree Name
Master of Science (MS)
College
Pharmacy
Department/School/Program
Pharmaceutical Sciences
Faculty
Dr. Björn Bauer
Faculty
Dr. David Feola
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
