TY  - JOUR
PY  - 2016//
TI  - Minimal traumatic brain injury in mice: protease-activated receptor 1 and thrombin-related changes
JO  - Journal of neurotrauma
A1  - Itsekson-Hayosh, Zeev
A1  - Shavit-Stein, Efrat
A1  - Katzav, Aviva
A1  - Rubovitch, Vardit
A1  - Maggio, Nicola
A1  - Chapman, Joab
A1  - Harnof, Sagi
A1  - Pick, Chaim G.
SP  - 1848
EP  - 1854
VL  - 33
IS  - 20
N2  - 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.<p />  <p>Language: en</p>
LA  - en
SN  - 0897-7151
UR  - http://dx.doi.org/10.1089/neu.2015.4146
ID  - ref1
ER  -