A novel treatment strategy for glioblastoma multiforme and glioma associated seizures: increasing glutamate uptake with PPARγ agonists

Jared Ching; Stephanie Amiridis; Stanley S Stylli; Andrew P Morokoff; Terence J O'Brien; Andrew H Kaye

doi:10.1016/j.jocn.2014.09.001

A novel treatment strategy for glioblastoma multiforme and glioma associated seizures: increasing glutamate uptake with PPARγ agonists

J Clin Neurosci. 2015 Jan;22(1):21-8. doi: 10.1016/j.jocn.2014.09.001. Epub 2014 Nov 22.

Authors

Jared Ching¹, Stephanie Amiridis², Stanley S Stylli³, Andrew P Morokoff³, Terence J O'Brien⁴, Andrew H Kaye³

Affiliations

¹ Department of Surgery, The University of Melbourne, Royal Melbourne Hospital, VIC, Australia; Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, VIC, Australia; Institute of Medical Sciences, Foresterhill, University of Aberdeen, Aberdeen AB25 2ZD, UK. Electronic address: [email protected].
² Department of Surgery, The University of Melbourne, Royal Melbourne Hospital, VIC, Australia; Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, VIC, Australia.
³ Department of Surgery, The University of Melbourne, Royal Melbourne Hospital, VIC, Australia; Department of Neurosurgery, The Royal Melbourne Hospital, Parkville, VIC, Australia.
⁴ Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, VIC, Australia.

PMID: 25439749
DOI: 10.1016/j.jocn.2014.09.001

Abstract

The established role of glutamate in the pathogenesis of glioma-associated seizures (GAS) led us to investigate a novel treatment method using an established drug class, peroxisome proliferator activated receptor (PPAR) gamma agonists. Previously, sulfasalazine has been shown to prevent release of glutamate from glioma cells and prevent GAS in rodent models. However, raising protein mediated glutamate transport via excitatory amino acid transporter 2 (EAAT2) has not been investigated previously to our knowledge. PPAR gamma agonists are known to upregulate functional EAAT2 expression in astrocytes and prevent excitotoxicity caused by glutamate excess. These agents are also known to have anti-neoplastic mechanisms. Herein we discuss and review the potential mechanisms of these drugs and highlight a novel potential treatment for GAS.

Keywords: Glioma; Glutamate; PPAR gamma; Seizures.

Publication types

Review

MeSH terms

Animals
Antineoplastic Agents / pharmacology*
Brain Neoplasms / complications
Brain Neoplasms / drug therapy*
Excitatory Amino Acid Transporter 2 / metabolism*
Glioblastoma / complications
Glioblastoma / drug therapy*
Glutamic Acid / metabolism*
Humans
PPAR gamma / agonists*
PPAR gamma / metabolism
Seizures / drug therapy*
Seizures / etiology

Substances

Antineoplastic Agents
Excitatory Amino Acid Transporter 2
PPAR gamma
Glutamic Acid