In vivo KPT-350 treatment decreases cortical hyperexcitability following traumatic brain injury

Brain Inj. 2020 Sep 18;34(11):1489-1496. doi: 10.1080/02699052.2020.1807056. Epub 2020 Aug 27.


Primary objective: We tested whether KPT-350, a novel selective inhibitor of nuclear export, could attenuate cortical network hyperexcitability, a major risk factor for developing post-traumatic epilepsy (PTE) following traumatic brain injury (TBI).

Research design: All mice in this study underwent TBI and were subsequently treated with either KPT-350 or vehicle during the post-injury latent period. Half of the animal cohort was used for electrophysiology while the other half was used for immunohistochemical analysis.

Methods and procedures: TBI was induced using the controlled cortical impact (CCI) model. Cortical network activity was recorded by evoking field potentials from deep layers of the cortex and analyzed using Matlab software. Immunohistochemistry coupled with fluorescence microscopy and Image J analysis detected changes in neuronal and glial markers.

Main outcomes and results: KPT-350 attenuated TBI-associated epileptiform activity and restored disrupted input-output responses in cortical brain slices. In vivo KPT-350 treatment reduced the loss of parvalbumin-(+) GABAergic interneurons after CCI but did not significantly change CCI-induced loss of somatostatin-(+) GABAergic interneurons, nor did it reduce reactivity of GFAP and Iba1 glial markers.

Conclusion: KPT-350 can prevent cortical hyperexcitability and reduce the loss of parvalbumin-(+) GABAergic inhibitory neurons, making it a potential therapeutic option for preventing PTE.

Keywords: Traumatic brain injury; XPO1 inhibitors; epilepsy; neuronal hyperexcitability; selective inhibitors of nuclear export.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Injuries, Traumatic* / complications
  • Brain Injuries, Traumatic* / drug therapy
  • Disease Models, Animal
  • GABAergic Neurons
  • Interneurons
  • Mice
  • Parvalbumins


  • Parvalbumins