Yan Yuhui, Shen Feng-Yi, Agresti Michael, Zhang Lin-Ling, Matloub Hani S, LoGiudice John A, Havlik Robert, Li Jifeng, Gu Yu-Dong, Yan Ji-Geng
Department of Plastic and Reconstructive Surgery, Medical College of Wisconsin, Milwaukee.
Froedtert Health-Community Memorial Hospital, Medical College of Wisconsin, Milwaukee.
J Neurosci Res. 2017 Sep;95(9):1786-1795. doi: 10.1002/jnr.24009. Epub 2017 Jan 4.
Peripheral nerve injury can have a devastating effect on daily life. Calcium concentrations in nerve fibers drastically increase after nerve injury, and this activates downstream processes leading to neuron death. Our previous studies showed that calcium-modulating agents decrease calcium accumulation, which aids in regeneration of injured peripheral nerves; however, the optimal therapeutic window for this application has not yet been identified. In this study, we show that calcium clearance after nerve injury is positively correlated with functional recovery in rats suffering from a crushed sciatic nerve injury. After the nerve injury, calcium accumulation increased. Peak volume is from 2 to 8 weeks post injury; calcium accumulation then gradually decreased over the following 24-week period. The compound muscle action potential (CMAP) measurement from the extensor digitorum longus muscle recovered to nearly normal levels in 24 weeks. Simultaneously, real-time polymerase chain reaction results showed that upregulation of calcium-ATPase (a membrane protein that transports calcium out of nerve fibers) mRNA peaked at 12 weeks. These results suggest that without intervention, the peak in calcium-ATPase mRNA expression in the injured nerve occurs after the peak in calcium accumulation, and CMAP recovery continues beyond 24 weeks. Immediately using calcium-modulating agents after crushed nerve injury improved functional recovery. These studies suggest that a crucial time frame in which to initiate effective clinical approaches to accelerate calcium clearance and nerve regeneration would be prior to 2 weeks post injury. © 2017 Wiley Periodicals, Inc.
周围神经损伤会对日常生活产生毁灭性影响。神经损伤后神经纤维中的钙浓度会急剧增加，这会激活导致神经元死亡的下游过程。我们之前的研究表明，钙调节剂可减少钙的积累，这有助于受损周围神经的再生；然而，该应用的最佳治疗窗口尚未确定。在本研究中，我们表明神经损伤后的钙清除与坐骨神经挤压伤大鼠的功能恢复呈正相关。神经损伤后，钙积累增加。峰值出现在损伤后2至8周；随后在接下来的24周内钙积累逐渐减少。来自趾长伸肌的复合肌肉动作电位（CMAP）测量在24周内恢复到几乎正常水平。同时，实时聚合酶链反应结果显示，钙ATP酶（一种将钙转运出神经纤维的膜蛋白）mRNA的上调在12周时达到峰值。这些结果表明，在没有干预的情况下，受损神经中钙ATP酶mRNA表达的峰值出现在钙积累峰值之后，并且CMAP恢复在24周后仍在继续。在挤压神经损伤后立即使用钙调节剂可改善功能恢复。这些研究表明，启动有效临床方法以加速钙清除和神经再生的关键时间框架是在损伤后2周之前。© 2017威利期刊公司。
