Profound deficits in hippocampal synaptic plasticity after traumatic brain injury and seizure is ameliorated by prophylactic levetiracetam

Yuan Hao Chen, Tung Tai Kuo, Eagle Yi Kung Huang, Barry J. Hoffer, Yu Ching Chou, Yung Hsiao Chiang, Hsin I. Ma, Jonathan P. Miller

Research output: Contribution to journalArticle

Abstract

Aim: To determine the precise effects of post-traumatic seizure activity on hippocampal processes, we induced seizures at various intervals after traumatic brain injury (TBI) and analyzed plasticity at CA1 Schaffer collateral synapses. Material and Methods: Rats were initially separated into two groups; one exposed solely to fluid percussion injury (FPI) at 2 Psi and the other only receiving kainic acid (KA)-induced seizures without FPI. Electrophysiological (ePhys) studies including paired-pulse stimulation for short-term presynaptic plasticity and long-term potentiation (LTP) of CA1 Schaffer collateral synapses of the hippocampus for postsynaptic function survey were followed at post-event 1 hour, 3 and 7 days respectively. Additional rats were exposed to three seizures at weekly intervals starting 1 week or 2 weeks after TBI and compared with seizures without TBI, TBI without seizures, and uninjured animals. An additional group placed under the same control variables were treated with levetiracetam prior to seizure induction. The ePhys studies related to post-TBI induced seizures were also followed in these additional groups. Results: Seizures affected the short- and long-term synaptic plasticity of the hippocampal CA3-CA1 pathway. FPI itself suppressed LTP and field excitatory post synaptic potentials (fEPSP) in the CA1 Schaffer collateral synapses; KA-induced seizures that followed FPI further suppressed synaptic plasticity. The impairments in both short-term presynaptic and long-term plasticity were worse in the rats in which early post-TBI seizures were induced than those in which later post-TBI seizures were induced. Finally, prophylactic infusion of levetiracetam for one week after FPI reduced the synaptic plasticity deficits in early post-TBI seizure animals. Conclusion: Our data indicates that synaptic plasticity (i.e., both presynaptic and postsynaptic) suppression occurs in TBI followed by a seizure and that the interval between the TBI and seizure is an important factor in the severity of the resulting deficits. Furthermore, the infusion of prophylactic levetiracetam could partially reverse the suppression of synaptic plasticity.

LanguageEnglish
Pages11515-11527
Number of pages13
JournalOncotarget
Volume9
Issue number14
DOIs
StatePublished - Feb 20 2018

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etiracetam
Neuronal Plasticity
Long-Term Potentiation
Hippocampus
Seizures
Percussion
Synapses
Wounds and Injuries
Kainic Acid
Traumatic Brain Injury

Keywords

  • Hippocampus
  • Long-term potentiation
  • Seizures
  • Short-term presynaptic plasticity
  • Traumatic brain injury

ASJC Scopus subject areas

  • Oncology

Cite this

Profound deficits in hippocampal synaptic plasticity after traumatic brain injury and seizure is ameliorated by prophylactic levetiracetam. / Chen, Yuan Hao; Kuo, Tung Tai; Huang, Eagle Yi Kung; Hoffer, Barry J.; Chou, Yu Ching; Chiang, Yung Hsiao; Ma, Hsin I.; Miller, Jonathan P.

In: Oncotarget, Vol. 9, No. 14, 20.02.2018, p. 11515-11527.

Research output: Contribution to journalArticle

Chen, Yuan Hao ; Kuo, Tung Tai ; Huang, Eagle Yi Kung ; Hoffer, Barry J. ; Chou, Yu Ching ; Chiang, Yung Hsiao ; Ma, Hsin I. ; Miller, Jonathan P./ Profound deficits in hippocampal synaptic plasticity after traumatic brain injury and seizure is ameliorated by prophylactic levetiracetam. In: Oncotarget. 2018 ; Vol. 9, No. 14. pp. 11515-11527
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AU - Kuo,Tung Tai

AU - Huang,Eagle Yi Kung

AU - Hoffer,Barry J.

AU - Chou,Yu Ching

AU - Chiang,Yung Hsiao

AU - Ma,Hsin I.

AU - Miller,Jonathan P.

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N2 - Aim: To determine the precise effects of post-traumatic seizure activity on hippocampal processes, we induced seizures at various intervals after traumatic brain injury (TBI) and analyzed plasticity at CA1 Schaffer collateral synapses. Material and Methods: Rats were initially separated into two groups; one exposed solely to fluid percussion injury (FPI) at 2 Psi and the other only receiving kainic acid (KA)-induced seizures without FPI. Electrophysiological (ePhys) studies including paired-pulse stimulation for short-term presynaptic plasticity and long-term potentiation (LTP) of CA1 Schaffer collateral synapses of the hippocampus for postsynaptic function survey were followed at post-event 1 hour, 3 and 7 days respectively. Additional rats were exposed to three seizures at weekly intervals starting 1 week or 2 weeks after TBI and compared with seizures without TBI, TBI without seizures, and uninjured animals. An additional group placed under the same control variables were treated with levetiracetam prior to seizure induction. The ePhys studies related to post-TBI induced seizures were also followed in these additional groups. Results: Seizures affected the short- and long-term synaptic plasticity of the hippocampal CA3-CA1 pathway. FPI itself suppressed LTP and field excitatory post synaptic potentials (fEPSP) in the CA1 Schaffer collateral synapses; KA-induced seizures that followed FPI further suppressed synaptic plasticity. The impairments in both short-term presynaptic and long-term plasticity were worse in the rats in which early post-TBI seizures were induced than those in which later post-TBI seizures were induced. Finally, prophylactic infusion of levetiracetam for one week after FPI reduced the synaptic plasticity deficits in early post-TBI seizure animals. Conclusion: Our data indicates that synaptic plasticity (i.e., both presynaptic and postsynaptic) suppression occurs in TBI followed by a seizure and that the interval between the TBI and seizure is an important factor in the severity of the resulting deficits. Furthermore, the infusion of prophylactic levetiracetam could partially reverse the suppression of synaptic plasticity.

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