Reversal of trauma-induced amnesia in mice by a thrombin receptor antagonist

Journal of Molecular Neuroscience : MN
Zeev ItzeksonJoab Chapman

Abstract

Minimal traumatic brain injury (mTBI) is associated with the existence of retrograde amnesia and microscopic bleeds containing activated coagulation factors. In an mTBI model, we report that thrombin induces amnesia through its receptor protease-activated receptor 1 (PAR-1). Thrombin activity was significantly elevated (32 %, p < 0.05) 5 min following mTBI compared to controls. Amnesia was assessed by the novel object recognition test in mTBI animals and in animals injected intracerebroventricularly (ICV) with either thrombin or a PAR-1 agonist 1 h after the acquisition phase. Saline-injected controls had a preference index of over 0.3 while mTBI animals and those injected with thrombin or the PAR-1 agonist spent equal time with both objects indicating no recall of the object presented to them 24 h previously (p < 0.05). Co-injecting a PAR-1 antagonist (SCH79797) completely blocked the amnestic effects of mTBI, thrombin, and the PAR-1 agonist. Long-term potentiation, measured in hippocampal slices 24 h after mTBI, ICV thrombin or the PAR-1 agonist, was significantly impaired and this effect was completely reversed by the PAR-1 antagonist. The results support a crucial role for PAR-1 in the generation of amnesia following mTBI, ...Continue Reading

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Citations

Oct 21, 2016·Journal of Neurotrauma·Zeev Itsekson-HayoshChaim G Pick
Aug 23, 2016·Seminars in Cell & Developmental Biology·Denis Monard
Oct 25, 2016·Neuroscience·Orna GeraJoab Chapman
Oct 13, 2017·International Journal of Molecular Sciences·Ciro De LucaMichele Papa
Nov 15, 2017·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Chun-Shu PiaoMark S Wainwright
Jul 6, 2019·PloS One·Efrat Shavit-SteinAmir Dori
Aug 10, 2019·Neural Regeneration Research·Shany G Gofrit, Efrat Shavit-Stein
Feb 6, 2020·Frontiers in Pharmacology·Marina Ben ShimonNicola Maggio
May 1, 2021·Biomolecules·Nathan A ShlobinChaim G Pick

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