创伤性脑损伤和癫痫发作后海马体突触可塑性的严重缺陷可通过预防性左乙拉西坦得到改善。
Profound deficits in hippocampal synaptic plasticity after traumatic brain injury and seizure is ameliorated by prophylactic levetiracetam.
作者信息
Chen Yuan-Hao, Kuo Tung-Tai, Yi-Kung Huang Eagle, Hoffer Barry J, Chou Yu-Ching, Chiang Yung-Hsiao, Ma Hsin-I, Miller Jonathan P
机构信息
Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.
Graduate Institute of Computer and Communication Engineering, National Taipei University of Technology, Taipei, Taiwan, R.O.C.
出版信息
Oncotarget. 2018 Jan 4;9(14):11515-11527. doi: 10.18632/oncotarget.23923. eCollection 2018 Feb 20.
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.
目的
为确定创伤后癫痫活动对海马体过程的确切影响，我们在创伤性脑损伤（TBI）后的不同时间间隔诱发癫痫，并分析CA1区谢弗侧支突触的可塑性。
材料与方法
大鼠最初被分为两组；一组仅接受2 Psi的液压冲击伤（FPI），另一组仅接受 kainic 酸（KA）诱导的癫痫发作而无FPI。分别在事件发生后1小时、3天和7天进行电生理（ePhys）研究，包括用于短期突触前可塑性的配对脉冲刺激以及用于海马体CA1区谢弗侧支突触的突触后功能检测的长时程增强（LTP）。另外的大鼠在TBI后1周或2周开始，每隔一周接受三次癫痫发作，并与无TBI的癫痫发作组、有TBI但无癫痫发作组以及未受伤动物进行比较。在癫痫发作诱导前，对置于相同对照变量下的另一组大鼠给予左乙拉西坦治疗。在这些额外的组中也进行了与TBI后诱发癫痫相关的ePhys研究。
结果
癫痫发作影响海马体CA3-CA1通路的短期和长期突触可塑性。FPI本身抑制了CA1区谢弗侧支突触中的LTP和场兴奋性突触后电位（fEPSP）；FPI后KA诱导的癫痫发作进一步抑制了突触可塑性。与后期TBI后癫痫发作的大鼠相比，早期TBI后癫痫发作的大鼠在短期突触前和长期可塑性方面的损伤更严重。最后，FPI后预防性输注左乙拉西坦一周可减少早期TBI后癫痫发作动物的突触可塑性缺陷。
结论
我们的数据表明，TBI后继发癫痫发作时会出现突触可塑性（即突触前和突触后）抑制，并且TBI与癫痫发作之间的时间间隔是导致的缺陷严重程度的一个重要因素。此外，预防性输注左乙拉西坦可部分逆转突触可塑性的抑制。
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