Imipramine treatment increases cell proliferation following fluid percussion brain injury in rats

Abstract

Objective: Researchers have observed unsustainable neurogenesis of the dentate gyrus of the hippocampus, as well as cognitive improvements in short-term imipramine-treated mice following a controlled cortical impact (CCI) model of traumatic brain injury (TBI). But they have yet to investigate the effects of a longer-duration imipramine treatment. In this study, we investigated the effects of a longer treatment regimen on rats following a fluid percussion injury (FPI) model, which creates a brain injury that more closely resembles those incurred by human patients.

Methods: We administered imipramine to rats for 8 weeks following FPI. Brain histology was performed to measure neurogenesis and cognitive recovery was evaluated using the Morris water maze (MWM).

Results: The Injury+imipramine group demonstrated 172% neurogenesis relative to the injury alone group at 9+ weeks in the dentate gyrus of the hippocampus. Neurogenesis observed here involved both the injured and the uninjured sides of the brain. All four groups (FPI+imipramine, FPI, sham, sham+imipramine) showed a similar performance in the MWM task.

Discussion: Longer duration of treatment with imipramine promotes sustained increase in hippocampal cell proliferation and survival. Global neurogenesis corresponds to the diffuse nature of FPI injury. Cognitive outcome can be due to a delay in our behavior testing as much as an absence of cognitive benefit of imipramine at this stage of neurogenesis. Nevertheless, exploring the potential benefits of prophylactic antidepressant treatment in human TBI patients is worthwhile.

Keywords:

• Imipramine
• Neurogenesis
• Traumatic brain injury
• Rats
• FPI