Tranexamic acid impairs hippocampal synaptic transmission mediated by gamma aminobutyric acid receptor type A

Hedwig Irl, Stephan Kratzer, Stefan Schwerin, Eberhard Kochs, Manfred Blobner, Gerhard Schneider, Gerhard Rammes, Rainer Haseneder

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


High-dose application of tranexamic acid (TXA), a widely used antifibrinolytic drug, can cause seizures in patients undergoing surgery. Mechanistically, seizures are considered to arise from an imbalance between inhibitory and excitatory synaptic transmission, whose main transmitters are gamma-aminobutyric acid (GABA) and glutamate. In the present study, we investigated the effects of TXA on neuronal excitability and synaptic transmission in the hippocampus, a structure that plays a pivotal role in human epilepsy. In acute slices of the murine hippocampus, fast depolarization-mediated imaging signals (FDSs) and postsynaptic currents (PSCs) were recorded using voltage-sensitive dye imaging and whole-cell patch clamp technique, respectively. FDSs and PSCs were evoked upon stimulation of the dentate gyrus and Schaffer collateral/associational commissural pathway, respectively. GABAA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and N-methyl-D-aspartate (NMDA) receptor-mediated postsynaptic currents were isolated pharmacologically. Application of TXA enhanced FDS propagation in the hippocampus. Neither the resting membrane potential of the investigated neurones nor synaptic transmission mediated by AMPA or NMDA receptors was changed by the application of 1 mM TXA. In contrast, TXA dose-dependently reduced GABAA receptor-mediated synaptic transmission. TXA induced the inhibition of GABAA receptor-mediated synaptic transmission in the hippocampus with a potency similar to that of its antagonistic properties against GABAA receptors in the basolateral amygdala (Kratzer et al., 2014). Since impairment of GABAergic transmission is a major cause of epileptic seizures, the observed effect might contribute to the proconvulsive properties of TXA.

Original languageEnglish
Pages (from-to)49-55
Number of pages7
JournalEuropean Journal of Pharmacology
StatePublished - 15 Nov 2017
Externally publishedYes


  • GABA
  • Hippocampus
  • Seizures
  • Tranexamic acid


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