Abstract
While zinc promotes motor function recovery after spinal cord injury (SCI), the precise mechanisms involved are not fully understood. The present study aimed to elucidate the effects of zinc and granulocyte colony stimulating factor (G-CSF) on neuronal recovery after SCI. The SCI model was established by Allen’s method. Injured animals were given glucose and zinc gluconate (ZnG; 30 mg/kg) for the first time at 2 h after injury, the same dose was given for 3 days. A cytokine antibody array was used to screen changes in inflammation at the site of SCI lesion. Immunofluorescence was used to detect the distribution of cytokines. Magnetic beads were also used to isolate cells from the site of SCI lesion. We then investigated the effect of Zinc on apoptosis after SCI by Transferase UTP Nick End Labeling (TUNEL) staining and Western Blotting. Basso Mouse Scale (BMS) scores and immunofluorescence were employed to investigate neuronal apoptosis and functional recovery. We found that the administration of zinc significantly increased the expression of 19 cytokines in the SCI lesion. Of these, G-CSF was shown to be the most elevated cytokine and was secreted by microglia/macrophages (M/Ms) via the nuclear factor-kappa B (NF-κB) signaling pathway after SCI. Increased levels of G-CSF at the SCI lesion reduced the level of neuronal apoptosis after SCI, thus promoting functional recovery. Collectively, our results indicate that the administration of zinc increases the expression of G-CSF secreted by M/Ms, which then leads to reduced levels of neuronal apoptosis after SCI.
Highlights
Spinal cord injury (SCI) is one of the most common central nervous system injuries encountered in clinic and is often accompanied with the loss of motor and sensory function
We found that zinc promotes SCI recovery by elevating brain-derived neurotrophic factor and by promoting microglia/macrophages (M/Ms) secreting the granulocyte colony stimulating factor (G-CSF) which protect the survival of neuron form the secondary injuries
We confirmed results arising from the cytokine protein array on the third day after injury, which showed that the expression of G-CSF in spinal cord after zinc treatment had increased in Western blotting (P < 0.01) and Quantitative Real-Time PCR Analysis (qRT-PCR) (1 day vs. 2 days, 2 days vs. 3 days, P < 0.001; Figures 1E–G)
Summary
Spinal cord injury (SCI) is one of the most common central nervous system injuries encountered in clinic and is often accompanied with the loss of motor and sensory function. Many enzymes and transcription factors exert their active function by creating covalent bonds with zinc ions (Kaur et al, 2014). Zinc is present throughout the central nervous system and plays a crucial role in synaptic transmission and neuroregulation, and is thought to be involved in neuroprotection (Ripps and Chappell, 2014). Many studies have shown that zinc is involved in neural diseases including depression, Parkinson’s disease, Alzheimer’s disease and lateral sclerosis of the spinal cord (Yasui et al, 1993; Nowak et al, 2005; Brewer et al, 2010). Following SCI, inflammation is the most overwhelming process and causes significant pathological changes, including apoptosis (Yeiser et al, 2002; Seth et al, 2015; Tian et al, 2018)
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