Activation of Sphingosine 1-Phosphate Receptor 1 Enhances Hippocampus Neurogenesis in a Rat Model of Traumatic Brain Injury: An Involvement of MEK/Erk Signaling Pathway

Figure 1

Schematic diagram of drugs and 5-bromo-2-deoxyuridine (BrdU) administration. The time-point of traumatic brain injury (TBI) model establishment was defined as zero point (indicated by black pentagram). (a) For the assay of neural stem cells (NSCs) proliferation, BrdU (100 mg/kg) was injected intraperitoneally (i.p.) three times with 8-hour interval at 6 days after TBI (indicated by black arrow) and the animals were sacrificed for perfusion at 7 days after TBI (indicated by black triangle). (b) For the analysis of NSCs differentiation, BrdU (100 mg/kg) was injected i.p. seven times with 24-hour interval 1–7 days after TBI (indicated by black arrow) and the animals were sacrificed for perfusion at 28 days after TBI (indicated by black triangle). SEW2871 (1.0 mg/kg/day) or VPC23019 (0.5 mg/kg/day) or vehicle (0.5 mL/kg/day) was administrated i.p. in rats of the corresponding group seven times within 24-hour interval 1–7 days after TBI (indicated by red arrow in (a) and (b)). Erucin (ERN, 12.5 mg/kg) or U0126 (0.2 mg/kg) was administrated i.p. or intravenously (i.v.) in rats of TBI+SEW+U0126 group 20 minutes before TBI (indicated by green arrow in (a) and (b)).

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