title: Minimal Traumatic Brain Injury in Mice: Protease-Activated Receptor 1 and Thrombin-Related Changes.
abstract: Minimal traumatic brain injury (mTBI) is partially defined by the existence of retrograde amnesia and is associated with microscopic bleeds containing activated coagulation factors. In a previous study, we have found that mTBI immediately releases thrombin-like activity in the brain, which induces amnesia by activating protease-activated receptor 1 (PAR-1) and blocking long-term potentiation (LTP). In the present study, we assessed the effects of mTBI on thrombin and PAR-1 levels in the brain using the same model. After the immediate elevation, thrombin activity returned to baseline 1 h post-trauma and increased again 72 h later (42% relative to control; p < 0.005). These changes were associated with a significant increase in PAR-1 levels 24 (17%; p < 0.05) and 72 h (20%; p < 0.05) post-trauma. Interestingly, the late elevation in thrombin-like activity was also associated with elevation of the major central nervous system thrombin inhibitor, protease nexin-1, 72 h post-mTBI (10%; p < 0.005). When thrombin was injected into brain ventricles, an increased sensitivity to seizure-like activity was detected at 72 h post-mTBI. The results are compatible with astrocyte activation post-mTBI resulting in increased thrombin secretion, PAR-1 expression, and seizure sensitivity.
authors.affiliation: 1 Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv, Israel .|2 Department of Neurology and Joseph Sagol Neuroscience Center, The Chaim Sheba Medical Center , Tel HaShomer, Israel .
authors.forename: Zeev
authors.initials: Z
authors.lastname: Itsekson-Hayosh
authors.affiliation: 1 Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv, Israel .|2 Department of Neurology and Joseph Sagol Neuroscience Center, The Chaim Sheba Medical Center , Tel HaShomer, Israel .
authors.forename: Efrat
authors.initials: E
authors.lastname: Shavit-Stein
authors.affiliation: 2 Department of Neurology and Joseph Sagol Neuroscience Center, The Chaim Sheba Medical Center , Tel HaShomer, Israel .
authors.forename: Aviva
authors.initials: A
authors.lastname: Katzav
authors.affiliation: 4 Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv, Israel .
authors.forename: Vardit
authors.initials: V
authors.lastname: Rubovitch
authors.affiliation: 2 Department of Neurology and Joseph Sagol Neuroscience Center, The Chaim Sheba Medical Center , Tel HaShomer, Israel .|3 The Talpiot Medical Leadership Program, The Chaim Sheba Medical Center , Tel HaShomer, Israel .|7 Department of Neurology, Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv, Israel .|8 Sagol School of Neuroscience, Tel Aviv University , Tel Aviv, Israel .
authors.forename: Nicola
authors.initials: N
authors.lastname: Maggio
authors.affiliation: 1 Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv, Israel .|2 Department of Neurology and Joseph Sagol Neuroscience Center, The Chaim Sheba Medical Center , Tel HaShomer, Israel .|6 Robert and Martha Harden Chair in Mental and Neurological Diseases, Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv, Israel .|8 Sagol School of Neuroscience, Tel Aviv University , Tel Aviv, Israel .
authors.forename: Joab
authors.initials: J
authors.lastname: Chapman
authors.affiliation: 5 Department of Neurosurgery, The Chaim Sheba Medical Center , Tel HaShomer, Israel .
authors.forename: Sagi
authors.initials: S
authors.lastname: Harnof
authors.affiliation: 4 Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv, Israel .|8 Sagol School of Neuroscience, Tel Aviv University , Tel Aviv, Israel .
authors.forename: Chaim G
authors.initials: CG
authors.lastname: Pick
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001924:Brain Concussion / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D044463:Receptor, PAR-1 / Q000378:metabolism*; D012640:Seizures / Q000209:etiology; D013917:Thrombin / Q000378:metabolism*
chemical_list: D044463:Receptor, PAR-1; D013917:Thrombin
keywords: PAR-1; astrocytes; mTBI; thrombin