The role of UCH-L1, MMP-9, and GFAP as peripheral markers of different susceptibility to seizure development in a preclinical model of epilepsy

Natalia Chmielewska; Piotr Maciejak; Danuta Turzyńska; Alicja Sobolewska; Aleksandra Wisłowska-Stanek; Karolina Kołosowska; Adam Płaźnik; Janusz Szyndler

doi:10.1016/j.jneuroim.2019.03.018

The role of UCH-L1, MMP-9, and GFAP as peripheral markers of different susceptibility to seizure development in a preclinical model of epilepsy

J Neuroimmunol. 2019 Jul 15:332:57-63. doi: 10.1016/j.jneuroim.2019.03.018. Epub 2019 Mar 29.

Authors

Natalia Chmielewska¹, Piotr Maciejak², Danuta Turzyńska³, Alicja Sobolewska³, Aleksandra Wisłowska-Stanek⁴, Karolina Kołosowska³, Adam Płaźnik², Janusz Szyndler⁴

Affiliations

¹ Department of Neurochemistry, Institute of Psychiatry and Neurology, Sobieskiego Street 9, 02-957 Warsaw, Poland. Electronic address: nchmielewska@ipin.edu.pl.
² Department of Neurochemistry, Institute of Psychiatry and Neurology, Sobieskiego Street 9, 02-957 Warsaw, Poland; Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology CePT, Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland.
³ Department of Neurochemistry, Institute of Psychiatry and Neurology, Sobieskiego Street 9, 02-957 Warsaw, Poland.
⁴ Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology CePT, Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland.

PMID: 30952062
DOI: 10.1016/j.jneuroim.2019.03.018

Abstract

In our study, we assessed the potency of the brain-derived proteins ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), matrix metalloproteinase 9 (MMP-9), glial fibrillary acidic protein (GFAP) and the immune activation indicators interleukin 1β (IL-1β) and interleukin 6 (IL-6) as peripheral biomarkers of different susceptibilities to kindling in a preclinical model. We observed increased plasma UCH-L1 levels in kindled vs. control animals. Furthermore, MMP-9 and IL-1β concentrations were the lowest in rats resistant to kindling. In summary, UCH-L1 is an indicator of neuronal loss and BBB disruption after seizure. MMP-9 and IL-1β may indicate resistance to kindling. UCH-L1, MMP-9 and IL-1β may have utility as peripheral biomarkers with translational potency in the clinic.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biomarkers
Brain Chemistry*
Convulsants / toxicity
Disease Susceptibility
Glial Fibrillary Acidic Protein / blood*
Interleukin-1beta / blood
Interleukin-6 / blood
Kindling, Neurologic / drug effects
Kindling, Neurologic / metabolism
Male
Matrix Metalloproteinase 9 / blood*
Models, Animal
Pentylenetetrazole / toxicity
Rats
Rats, Wistar
Seizures / blood*
Seizures / chemically induced
Ubiquitin Thiolesterase / blood*

Substances

Biomarkers
Convulsants
GFAP protein, rat
Glial Fibrillary Acidic Protein
Il6 protein, rat
Interleukin-1beta
Interleukin-6
UCHL1 protein, rat
Ubiquitin Thiolesterase
Matrix Metalloproteinase 9
Pentylenetetrazole