Objective: To investigate the roles of protease-activated receptors (PARs) in thrombin-induced brain injury and neurogenesis in rats.
Methods: Ninety male SD rats were randomly assigned to receive intra-hippocampus injection of NS, thrombin or specific agonists of 3 protease-activated receptors (PAR-1, PAR-3 and PAR-4), respectively. At 1,3 and 7 d after injection, the area of the hippocampus was determined with HE staining, the density and morphology of astrocyte were detected with GFAP staining, degenerated neurons were detected with Fluoro-Jade C staining, and the neurogenesis was examined with DCX staining.
Results: Compared to NS injection, the area of the hippocampus significantly increased at 1-3 d and decreased at 7 d after the injection of thrombin and PAR-1 agonist (P<0.05). In addition, injection of thrombin and PAR-1 agonist significantly increased the density of astrocyte and Fluoro-Jade C positive cells at 1-7 d after injection (P<0.05), and significantly increased the density of DCX positive cells at 3-7 d after injection(P<0.05). The injection of PAR-3 agonist and PAR-4 agonist had no affect on the area of the hippocampus, the density of astrocyte, Fluoro-Jade C positive cells and DCX positive cells.
Conclusion: The activation of protease-activated receptor-1 may be related to the thrombin-induced brain injury and neurogenesis in rat hippocampus.
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J Pharmacol Sci
February 2025
Department of Physical Chemistry for Bioactive Molecules, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 985-1 Sanzo, Higashimura-cho, Fukuyama, Hiroshima, 729-0292, Japan.
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Center for Cardiovascular Regeneration, Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX, USA.
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Department of Neurology, Tianjin Neurological Institute, Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Tianjin Medical University General Hospital, Tianjin, China.
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