Profound deficits in hippocampal synaptic plasticity after traumatic brain injury and seizure is ameliorated by prophylactic levetiracetam
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Yuan-Hao Chen1, Tung-Tai Kuo2, Eagle Yi-Kung Huang3, Barry J. Hoffer1,4,6, Yu-Ching Chou5, Yung-Hsiao Chiang6, Hsin-I Ma1 and Jonathan P. Miller4
1Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.
2Graduate Institute of Computer and Communication Engineering, National Taipei University of Technology, Taipei, Taiwan, R.O.C.
3Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, R.O.C.
4Department of Neurosurgery, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
5School of Public Health, National Defense Medical Center, Taipei, Taiwan, R.O.C.
6Division of Neurosurgery, The Ph.D. Program for Neural Regenerative Medicine, Taipei Medical University Hospital, Taipei, Taiwan, R.O.C.
Yuan-Hao Chen, email: [email protected]
Keywords: short-term presynaptic plasticity; traumatic brain injury; seizures; hippocampus; long-term potentiation
Received: September 04, 2017 Accepted: October 29, 2017 Published: January 04, 2018
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 post-synaptic 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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