• Kai-Ting Chang, Yi-Lo Lin, Chi-Te Lin, Chen-Jei Hong, Yung-Hsin Cheng, May-Jywan Tsai, Wen-Cheng Huang, Yang-Hsin Shih, Yi-Yen Lee, Henrich Cheng, and Ming-Chao Huang.
• Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
• Neurosurgery. 2020 Sep 15; 87 (4): 823-832.

BackgroundPreganglionic cervical root transection (PCRT) is the most severe type of brachial plexus injury. In some cases, surgical procedures must be postponed for ≥3 wk until electromyographic confirmation. However, research works have previously shown that treating PCRT after a 3-wk delay fails to result in functional recovery.ObjectiveTo assess whether the immunosuppressive drug sirolimus, by promoting neuroprotection in the acute phase of PCRT, could enable functional recovery in cases of delayed repair.MethodsFirst, rats received a left 6th to 8th cervical root transection, after which half were administered sirolimus for 1 wk. Markers of microglia, astrocytes, neurons, and autophagy were assessed at days 7 and 21. Second, animals with the same injury received nerve grafts, along with acidic fibroblast growth factor and fibrin glue, 3 wk postinjury. Sirolimus was administered to half of them for the first week. Mechanical sensation, grasping power, spinal cord morphology, functional neuron survival, nerve fiber regeneration, and somatosensory-evoked potentials (SSEPs) were assessed 1 and 23 wk postinjury.ResultsSirolimus was shown to attenuate microglial and astrocytic proliferation and enhance neuronal autophagy and survival; only rats treated with sirolimus underwent significant sensory and motor function recovery. In addition, rats who achieved functional recovery were shown to have abundant nerve fibers and neurons in the dorsal root entry zone, dorsal root ganglion, and ventral horn, as well as to have SSEPs reappearance.ConclusionSirolimus-induced neuroprotection in the acute stage of PCRT enables functional recovery, even if surgical repair is performed after a 3-wk delay.Copyright © 2020 by the Congress of Neurological Surgeons.

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