Edonerpic maleate prevents epileptic seizure during recovery from brain damage by balancing excitatory and inhibitory inputs.

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  • Additional Information
    • Source:
      Publisher: Frontiers Research Foundation Country of Publication: Switzerland NLM ID: 101477940 Publication Model: eCollection Cited Medium: Internet ISSN: 1662-5110 (Electronic) Linking ISSN: 16625110 NLM ISO Abbreviation: Front Neural Circuits Subsets: MEDLINE
    • Publication Information:
      Original Publication: [Lausanne, Switzerland] : Frontiers Research Foundation, c2007-
    • Subject Terms:
      Brain Injuries*/prevention & control ; Brain Injuries*/drug therapy; Animals ; Male ; Recovery of Function/drug effects ; Recovery of Function/physiology ; Seizures/prevention & control ; Seizures/chemically induced ; Seizures/drug therapy ; Rats ; Excitatory Postsynaptic Potentials/drug effects ; Excitatory Postsynaptic Potentials/physiology ; Maleates/pharmacology ; Epilepsy/chemically induced ; Epilepsy/prevention & control ; Rats, Sprague-Dawley
    • Abstract:
      Functional recovery from brain damage, such as stroke, is a plastic process in the brain. The excitatory glutamate α -amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) plays a crucial role in neuronal functions, and the synaptic trafficking of AMPAR is a fundamental mechanism underlying synaptic plasticity. We recently identified a collapsin response mediator protein 2 (CRMP2)-binding compound, edonerpic maleate, which augments rehabilitative training-dependent functional recovery from brain damage by facilitating experience-driven synaptic delivery of AMPARs. In animals recovering from cryogenic brain injury, a potential compensatory area adjacent to the injured region was observed, where the injection of CNQX, an AMPAR antagonist, significantly attenuated functional recovery. In the compensatory brain area of animals recovering from cryogenic injury, the administration of edonerpic maleate enhanced both excitatory and inhibitory synaptic inputs at pyramidal neurons. In contrast, recovered animals that did not receive the drug exhibited augmentation of only excitatory synaptic input. The threshold of picrotoxin-induced epileptic seizure in recovered animals without edonerpic maleate treatment was lower than in intact animals and recovered animals with edonerpic maleate. Thus, edonerpic maleate enhances motor function recovery from brain damage by balancing excitatory and inhibitory synaptic inputs, which helps prevent epileptic seizures during recovery.
      Competing Interests: Takuya Takahashi is one of the inventors of the patent application claiming the use of edonerpic maleate to enhance the functional recovery after brain damage [substance patent (WO03/03567, Alkyl ether derivatives or salts thereof) and use patent (WO/2015115582, post-nerve injury rehabilitation effect-enhancing agent comprising alkyl ether derivative or salt thereof)]. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
      (Copyright © 2024 Katsuno, Jitsuki, Ota, Yamanoue, Abe and Takahashi.)
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    • Contributed Indexing:
      Keywords: AMPA receptors; brain damage; edonerpic maleate; epileptic seizure; functional recovery; stroke; synaptic plasticity
    • Accession Number:
      0 (Maleates)
    • Publication Date:
      Date Created: 20241223 Date Completed: 20241223 Latest Revision: 20250104
    • Publication Date:
      20250104
    • Accession Number:
      PMC11660091
    • Accession Number:
      10.3389/fncir.2024.1492043
    • Accession Number:
      39712974