Department of Chemistry & Biochemistry, University of Arkansas, Fayetteville, AR, United States.
International Experimental Central Nervous System Injury & Repair (IECNSIR), Department of Surgical Sciences, Anesthesiology & Intensive Care Medicine, Uppsala University Hospital, Uppsala University, Uppsala, Sweden.
Prog Brain Res. 2020;258:397-438. doi: 10.1016/bs.pbr.2020.09.012. Epub 2020 Nov 12.
Spinal cord evoked potentials (SCEP) are good indicators of spinal cord function in health and disease. Disturbances in SCEP amplitudes and latencies during spinal cord monitoring predict spinal cord pathology following trauma. Treatment with neuroprotective agents preserves SCEP and reduces cord pathology after injury. The possibility that cerebrolysin, a balanced composition of neurotrophic factors improves spinal cord conduction, attenuates blood-spinal cord barrier (BSCB) disruption, edema formation, and cord pathology was examined in spinal cord injury (SCI). SCEP is recorded from epidural space over rat spinal cord T9 and T12 segments after peripheral nerves stimulation. SCEP consists of a small positive peak (MPP), followed by a prominent negative peak (MNP) that is stable before SCI. A longitudinal incision (2mm deep and 5mm long) into the right dorsal horn (T10 and T11 segments) resulted in an immediate long-lasting depression of the rostral MNP with an increase in the latencies. Pretreatment with either cerebrolysin (CBL 5mL/kg, i.v. 30min before) alone or TiO nanowired delivery of cerebrolysin (NWCBL 2.5mL/kg, i.v.) prevented the loss of MNP amplitude and even enhanced further from the pre-injury level after SCI without affecting latencies. At 5h, SCI induced edema, BSCB breakdown, and cell injuries were significantly reduced by CBL and NWCBL pretreatment. Interestingly this effect on SCEP and cord pathology was still prominent when the NWCBL was delivered 2min after SCI. Moreover, expressions of c-fos and c-jun genes that are prominent at 5h in untreated SCI are also considerably reduced by CBL and NWCBL treatment. These results are the first to show that CBL and NWCBL enhanced SCEP activity and thwarted the development of cord pathology after SCI. Furthermore, NWCBL in low doses has superior neuroprotective effects on SCEP and cord pathology, not reported earlier. The functional significance and future clinical potential of CBL and NWCBL in SCI are discussed.
脊髓诱发电位（SCEP）是健康和疾病中脊髓功能的良好指标。在脊髓监测过程中，SCEP 幅度和潜伏期的变化预测创伤后脊髓病理学。神经保护剂的治疗可保留 SCEP 并减少损伤后的脊髓病理学。神经生长因子（NTF）平衡组成的脑活素改善脊髓传导，减轻血脊髓屏障（BSCB）破坏、水肿形成和脊髓病理学的可能性，在脊髓损伤（SCI）中进行了检查。SCEP 是从大鼠脊髓 T9 和 T12 段的硬膜外间隙记录的，外周神经刺激后。SCEP 由一个小的正峰（MPP）组成，随后是一个显著的负峰（MNP），在 SCI 之前是稳定的。在右侧背角（T10 和 T11 节段）进行纵向切口（2mm 深，5mm 长）导致 MNP 的近端立即出现持久的抑制，潜伏期增加。单独用脑活素（CBL 5mL/kg，静脉注射 30min 前）预处理或用 TiO 纳米线输送脑活素（NWCBL 2.5mL/kg，静脉注射）可防止 MNP 幅度的丧失，甚至在 SCI 后从损伤前水平进一步增强，而不影响潜伏期。在 5 小时时，CBL 和 NWCBL 预处理可显著减少 SCI 引起的水肿、BSCB 破坏和细胞损伤。有趣的是，当 NWCBL 在 SCI 后 2 分钟时输送时，对 SCEP 和脊髓病理学的这种影响仍然很明显。此外，未治疗的 SCI 中在 5 小时时表达的 c-fos 和 c-jun 基因也明显减少了 CBL 和 NWCBL 的治疗。这些结果是首次表明 CBL 和 NWCBL 增强了 SCEP 活性，并阻止了 SCI 后脊髓病理学的发展。此外，低剂量的 NWCBL 在 SCEP 和脊髓病理学方面具有优越的神经保护作用，这在以前的报道中尚未报道。讨论了 CBL 和 NWCBL 在 SCI 中的功能意义和未来的临床潜力。
