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The expression of inflammatory markers and their potential influence on efflux transporters in drug‐resistant mesial temporal lobe epilepsy tissue
Author(s) -
Weidner Lora D.,
Kannan Pavitra,
Mitsios Nicholas,
Kang Sun J.,
Hall Matthew D.,
Theodore William H.,
Innis Robert B.,
Mulder Jan
Publication year - 2018
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.14505
Subject(s) - translocator protein , microglia , neuroinflammation , abcg2 , transporter , inflammation , biology , epilepsy , pharmacology , atp binding cassette transporter , immunology , neuroscience , biochemistry , gene
Summary Objective The role of neuroinflammation in mesial temporal lobe epilepsy ( MTLE ), and how it relates to drug resistance, remains unclear. Expression levels of the inflammatory enzymes cyclooxygenase ( COX )‐1 and COX‐2 have been found to be increased in animal models of epilepsy. Knowing the cellular expression of COX ‐1 and COX ‐2 is the key to understanding their functional role; however, only 3 studies have investigated COX ‐2 expression in epilepsy in humans, and there are no reports on COX ‐1. In addition, previous studies have shown that certain inflammatory proteins up‐regulate ATP binding cassette ( ABC ) transporter expression (thought to be responsible for drug resistance), but this relationship remains unclear in human tissue. This study sought to measure the expression of COX ‐1, COX ‐2, and translocator protein 18 kDa ( TSPO , an inflammation biomarker acting as a positive control), as well as ABC transporters P‐glycoprotein (P‐gp) and breast cancer resistance protein ( BCRP ), in brain tissue samples from people with drug‐resistant MTLE . Methods Formalin‐fixed paraffin‐embedded surgical brain tissue was obtained from 33 patients with drug‐resistant MTLE . Multiplex immunofluorescence was used to quantify the expression and distribution of COX ‐1, COX ‐2, TSPO , P‐gp, and BCRP . Results COX ‐1 was expressed in microglia, and COX ‐2 and TSPO were expressed in microglia and neurons. BCRP density correlated significantly with TSPO density, suggesting a potential relationship between inflammatory markers and efflux transporters. Significance To the best of our knowledge, this study is the first to measure the cellular expression of COX ‐1, COX ‐2, and TSPO in microglia, astrocytes, and neurons in surgical brain tissue samples from patients with drug‐resistant MTLE . Further research is needed to determine the effects of the COX inflammatory pathway in epilepsy, and how it relates to the expression of the ABC transporters P‐gp and BCRP .