Cystine/glutamate transporter SLC7A11 in canine tumour associated epilepsy, a new target for antiepileptic drugs?

Introduction:

Glioma patients frequently suffer from tumour-associated epilepsy (TAE), pathomechanisms of which are incompletely understood. One hypothesis suggests that tumour-induced epileptogenesis might employ the cystine/glutamate transporter SLC7A11 for glutamate release. As it can be pharmacologically targeted, we investigated its expression and its association to TAE in dogs affected by neuroglial tumors.

Materials and methods:

Twenty-four patients with (15/24) and without TAE (9/24) were investigated for cerebral SLC7A11 expression via immunohistochemistry. Immunopositivity was assessed semiquantitatively (1) within the tumour, (2) peritumoural and (3) within remote brain parenchyma.

Results:

SLC7A11 was expressed by all patients. In general, intratumoural expression was evident in oligodendrogliomas and higher than that of astrocytomas but it did not correlate to seizure prevalence or tumour grade. The peritumoural and remote expression fraction was significantly higher in TAE patients compared to non-epileptic dogs.

Discussion:

TAE brains show an increased SLC7A11 expression in the perilesional and remote brain parenchyma. As a surrogate of hyperexcitability, SLC7A11 further supports the concept of distant ictal-onset zone triggered by epileptogenic lesions and might open the door for new TAE therapies.