Investigating anti-inflammatory and immunomodulatory properties of brivaracetam and lacosamide in experimental autoimmune encephalomyelitis (EAE)

Abstract

Purpose: Inflammation plays a role in drug-resistant epilepsy (DRE). We have previously reported an increased proportion of CD4 T cells displaying a pro-inflammatory profile in the peripheral blood of adults with DRE. Specific anti-epileptic drugs (AEDs) exhibit immunomodulatory properties that could increase the risk of infections but also contribute to their beneficial impact on DRE and other neurological diseases. The impact of novel generation AEDs on the profile of immune cells and on neuroinflammatory processes remains unclear.

Methods: We compared the influence of brivaracetam and lacosamide on the activation of human and murine peripheral immune cells in vitro and in vivo in active experimental autoimmune encephalomyelitis (EAE), a common mouse model of central nervous system inflammation.

Results: We found that brivaracetam and lacosamide at 2.5 μg/ml did not impair the survival and activation of human immune cells, but a higher dose of 25 μg/ml decreased mitogen-induced proliferation of CD8 T cells in vitro. Exposure to high doses of brivaracetam, and to a lesser extent lacosamide, reduced the proportion of CD25⁺ and CD107a⁺ CD8⁺ human T cells in vitro, and the frequency of CNS-infiltrating CD8⁺ T cells at EAE onset and CD11b⁺ myeloid cells at peak in vivo. Prophylactic administration of brivaracetam or lacosamide did not delay EAE onset but significantly improved the clinical course in the chronic phase of EAE compared to control.

Conclusion: Novel generation AEDs do not impair the response to immunization with MOG peptide but improve the course of EAE, possibly through a reduction of neuroaxonal damage.

Keywords: Brivaracetam; Epilepsy; Experimental autoimmune encephalomyelitis; Lacosamide; Neuroinflammation.