Contribution of neuronal regeneration in the hippocampus and dentate gyrus to the memory disturbance after traumatic brain injury

以大鼠左侧顶叶皮质为受试区，采用中度液压冲击法造成实验性脑损伤动物模型。取FPI大鼠海马CA 1区和齿状回脑片。用电压敏感染料（RH-482）的光反应表明，刺激Schaffer侧支或穿支通路引起兴奋性光信号传播到海马CA 1区或齿状回（DG）。细胞内记录表明，FPI增强兴奋性突触后电位（EPSP）的幅度和持续时间。荷包牡丹碱（15 μM）可进一步增强FPI大鼠海马神经元的EPSP。FPI显著抑制海马CA 1区长时程增强（LTP）。FPI大鼠的长期抑郁（LTD）表现相对明显。但FPI对海马CA 1区和齿状回单个神经元的电生理特性无明显影响。FPI后谷氨酸神经元无明显出芽。腹膜内（i. p.）在FPI后30-90分钟给予地西泮（苯二氮卓衍生物）保护海马CA 1区免受头部损伤。在FPI大鼠中，地西泮和依达拉奉（一氧化氮清除剂）可选择性抑制场EPSP（fEPSP）的NMDA受体成分。低温（35℃）也能减轻FPI诱导的海马CA 1区神经元的兴奋。在FPI后早期（30-90 min）给予依达拉奉可防止FPI诱导的海马CA 1区神经元过度活动和病理性LTP。

Animal model of experimental brain injury was made by application of moderate fluid percussion injury (FPI) to the left parietal cortex of rat brain. Horizontal brain slices of hippocampal CA1 area and dentate gyrus were obtained from FPI rats. Optical responses with voltage-sensitive dye (RH-482) showed that stimulation of the Schaffer collaterals or perforant path evoked the propagation of excitatory optical signals to hippocampal CA1 area or dentate gyrus (DG). Intracellular recordings showed that FPI enhanced the amplitude and duration of excitatory postsynaptic potentials (EPSPs). The EPSP was further enhanced by bicuculline (15 μM) in FPI rat hippocampal neurons. FPI strongly depressed long-term potentiation (LTP) in hippocampal CA1 area. Long-term depression (LTD) was relatively obvious in FPI rats. However, electrophysiological properties of single neurons in the CA1 and the DG were not obviously altered by FPI. No obvious sprouting of glutamate neurons occurred after FPI. Intraperitoneal (i.p.) administration of diazepam (a benzodiazepine derivative) 30-90 min after FPI protected hippocampal CA1 area against the head injury. The NMDA-receptor component of the field EPSP (fEPSP) was selectively depressed by diazepam and edaravone, a nitric oxide scavenger, in FPI rats. Hypothermia (35℃) also attenuated the FPI-induced hyperactivity of hippocampal CA1 neurons. Administration of edaravone at early period (30-90 min) after FPI, prevented the FPI-induced hyperactivity and pathological LTP in hippocampal CA1 neurons.