Impairment of synaptic plasticity in hippocampus is exacerbated by methylprednisolone in a rat model of traumatic brain injury

Brain Res. 2011 Mar 25:1382:165-72. doi: 10.1016/j.brainres.2011.01.065. Epub 2011 Jan 26.


Patients with traumatic brain injury (TBI) exhibit impaired cognitive capability that is exacerbated with methylprednisolone (MP). Since long-term potentiation (LTP) is a leading cellular model underlying learning, we hypothesize that MP disturbs the electrophysiological character in the hippocampus by decreasing the number of interneurons post-traumatically in the dentate gyrus (DG) and cornu ammonis3 (CA3) regions, resulting in learning deficits. To test this hypothesis, we investigated the alterations of learning abilities and correlated the alternation with hippocampal synaptic plasticity in rats receiving lateral fluid percussion injury (FPI) and being treated with MP. We found that MP aggravates the spatial learning deficiency and changes in the excitability of the DG and cornu ammonis1 (CA1) areas in rats subjected to FPI. The functional and electrophysiological deficits are associated with a decrease in the number of parvalbumin-immunoreactive (PV-IR) and cholecystokinin-immunoreactive (CCK-IR) GABAergic cells. The data suggest that MP therapy may decrease the number of DG interneurons in post-traumatic hippocampus, resulting in the aggravated deficits of learning ability induced by TBI.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / toxicity*
  • Brain Injuries / drug therapy*
  • CA3 Region, Hippocampal / drug effects
  • CA3 Region, Hippocampal / pathology
  • CA3 Region, Hippocampal / physiopathology
  • Dentate Gyrus / drug effects
  • Dentate Gyrus / pathology
  • Dentate Gyrus / physiopathology
  • Disease Models, Animal
  • Hippocampus / drug effects*
  • Hippocampus / pathology
  • Hippocampus / physiopathology
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology
  • Male
  • Memory Disorders / chemically induced
  • Memory Disorders / pathology
  • Memory Disorders / physiopathology
  • Methylprednisolone / toxicity*
  • Nerve Degeneration / chemically induced*
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology
  • Neuronal Plasticity / drug effects*
  • Neuronal Plasticity / physiology
  • Rats
  • Rats, Wistar


  • Anti-Inflammatory Agents
  • Methylprednisolone