Effect of transgenic human insulin-like growth factor-1 on spinal motor neurons following peripheral nerve injury

Gu,Jiaxiang; Liu,Hongjun; Zhang,Naichen; Tian,Heng; Pan,Junbo; Zhang,Wenzhong; Wang,Jingcheng

doi:10.3892/etm.2015.2472

Effect of transgenic human insulin-like growth factor-1 on spinal motor neurons following peripheral nerve injury

Authors:
- Jiaxiang Gu
- Hongjun Liu
- Naichen Zhang
- Heng Tian
- Junbo Pan
- Wenzhong Zhang
- Jingcheng Wang
View Affiliations

Affiliations: Department of Hand Surgery, Clinical Medical Institute of Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China
Published online on: May 5, 2015 https://doi.org/10.3892/etm.2015.2472
Pages: 19-24
Copyright: © Gu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to observe the protective effect of exogenous human insulin‑like growth factor‑1 (hIGF‑1) on spinal motor neurons, following its local transfection into an area of peripheral nerve injury. A total of 90 male Wistar rats that had been established as sciatic nerve crush injury models were randomly divided into three groups: hIGF‑1 treatment, sham-transfected control and blank control groups. The different phases of hIGF‑1 expression were observed in the spinal cord via postoperative immunostaining and the apoptosis of motor neurons was observed using the terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling method. Pathological changes of the motor neurons and Nissl bodies within cell bodies were observed via Marsland and Luxol fast blue double staining, while changes in the neuropil of the spinal cord anterior horn were investigated via ultrastructural observation. It was found that hIGF‑1, locally transfected into an area of peripheral nerve injury, was expressed in the spinal anterior horn following axoplasmic transport; the peak hIGF‑1 expression occurred approximately a week following transfection. The number of apoptotic spinal cord motor neurons observed in the hIGF‑1 treatment group was fewer than that in the sham-transfected and blank control groups at days 7, 14 and 21 following transfection (P<0.01). Furthermore, the quantity of motor neuron cells in the anterior horn of the spinal cord in the hIGF‑1 treatment group was higher compared with those in the sham-transfected and blank control groups at days 2, 7, 14 and 28 following transfection (P<0.01). The degenerative changes of Nissl bodies within the cytoplasm of the hIGF‑1 treatment group were less severe compared with those of the sham‑transfected and blank control groups. At day 56 following transfection, the spinal anterior horn neuropil ultrastructure in the hIGF‑1 treatment group was generally normal, while the sham-transfected and blank control groups exhibited an increased number of protruding gaps and local cavities. These results indicate that the application of exogenous hIGF‑1 is capable of protecting spinal cord motor neurons following peripheral nerve injury.

View Figures

View References

1	Wang SR, Sun ZR, Dai YM, et al: Expression of ciliary neurotrophic factor of spinal cord motor neuron after sciatic nerve injury and changes after acupuncture intervention in rats. Zhongguo Zuzhi Gongcheng Yanjiu. 8:6954–6957. 2004.(In Chinese).
2	Bothwell M: Insulin and somatemedin MSA promote nerve growth factor-independent neurite formation by cultured chick dorsal root ganglionic sensory neurons. J Neurosci Res. 8:225–31. 1982. View Article : Google Scholar : PubMed/NCBI
3	Godińez-Gómez R, Trujillo-Hernández B, Tene CE, et al: Electrophysiological abnormalities in type 2 diabetic patients with reduced levels of insulin-like growth factor I. J Int Med Res. 34:21–29. 2006. View Article : Google Scholar : PubMed/NCBI
4	Zeng JZ, Dong KL, Li GC and Li LM: Effect of xiaokeling concentration fluid on mRNA expression of insulin-like growth factor-1 in sciatic nerve of Streptozotocin-induced diabetic rats. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 30:49–52. 2005.(In Chinese). PubMed/NCBI
5	Wang W, Teng Y, Zhang MQ, et al: Function of insulin receptor and insulin-like growth factor receptor in Alzheimer's disease. Sichuan Shengli Kexue Zazhi. 35:112–115. 2013.
6	Kiryakova S, Söhnchen J, Grosheva M, et al: Recovery of whisking function promoted by manual stimulation of the vibrissal muscles after facial nerve injury requires insulin-like growth factor 1 (IGF-1). Exp Neurol. 222:226–234. 2010. View Article : Google Scholar : PubMed/NCBI
7	Hu WL, Hu LQ, Li SW and Zheng XM: Reconstruction of erectile reflex circuit by autologous vein graft combined with use of insulin-like growth factor. Zhonghua Yi Xue Za Zhi. 84:1280–1282. 2004.(In Chinese). PubMed/NCBI
8	Emel E, Ergün SS, Kotan D, et al: Effects of insulin-like growth factor-1 and platelet-rich plasma on sciatic nerve crush injury in a rat model. J Neurosurg. 114:522–528. 2011. View Article : Google Scholar : PubMed/NCBI
9	Vögelin E, Baker JM, Gates J, Dixit V, Constantinescu MA and Jones NF: Effects of local continuous release of brain derived neurotrophic factor (BDNF) on peripheral nerve regeneration in a rat model. Exp Neurol. 199:348–353. 2006. View Article : Google Scholar : PubMed/NCBI
10	Lin YC, Oh SJ and Marra KG: Synergistic lithium chloride and glial cell line-derived neurotrophic factor delivery for peripheral nerve repair in a rodent sciatic nerve injury model. Plast Reconstr Surg. 132:251e–262e. 2013. View Article : Google Scholar : PubMed/NCBI
11	Zhang J, Lineaweaver WC, Oswald T, Chen Z, Chen Z and Zhang F: Ciliary neurotrophic factor for acceleration of peripheral nerve regeneration: an experimental study. J Reconstr Microsurg. 20:323–327. 2004. View Article : Google Scholar : PubMed/NCBI
12	Brinton RD and Wang JM: Therapeutic potential of neurogenesis for prevention and recovery from Alzheimer's disease: allopregnanolone as a proof of concept neurogenic agent. Curr Alzheimer Res. 3:185–190. 2006. View Article : Google Scholar : PubMed/NCBI
13	Saito I, Oka Y and Odaka M: Promoting nerve regeneration through long gaps using a small nerve tissue graft. Surg Neurol. 59:148–55. 2003. View Article : Google Scholar : PubMed/NCBI
14	Zhang P, Zhang C, Kou Y, et al: The histological analysis of biological conduit sleeve bridging rhesus monkey nerve injury with small gap. Artif Cells Blood Substit Immobil Biotechnol. 37:101–104. 2009. View Article : Google Scholar : PubMed/NCBI
15	Jiang B, Zhang P and Jiang B: Advances in small gap sleeve bridging peripheral nerve injury. Artif Cells Blood Substit Immobil Biotechnol. 38:1–4. 2010. View Article : Google Scholar : PubMed/NCBI
16	Zheng WH, Kar S, Doré S and Quirion R: Insulin-like growth factor-1 (IGF-1): a neuroprotective trophic factor acting via the Akt-kinase pathway. J Neural Transm Suppl. 60:261–272. 2000.PubMed/NCBI
17	Daughaday WH, Hall K, Salmon WD, Van den Brande JL and Van Wyk JJ: On the nomenclature of the somatomedins and insulin-like growth factors. Endocrinology. 121:1911–1922. 1987. View Article : Google Scholar : PubMed/NCBI
18	Rosen CJ and Pollak M: Circulating IGF-I: New perspectives for a new century. Trends Endocrinol Metab. 10:136–141. 1999. View Article : Google Scholar : PubMed/NCBI
19	Twigg SM and Baxter RC: Insulin-like growth factor (IGF)-binding protein 5 forms an alternative ternary complex with IGFs and the acid-labile subunit. J Biol Chem. 273:6074–6079. 1998. View Article : Google Scholar : PubMed/NCBI
20	Holman SR and Baxter RC: Insulin-like growth factor binding protein-3: factors affecting binary and ternary complex formation. Growth Regul. 6:42–47. 1996.PubMed/NCBI
21	Wolff JA, Malone RW, Williams P, et al: Direct gene transfer into mouse muscle in vivo. Science. 247:1465–1468. 1990. View Article : Google Scholar : PubMed/NCBI
22	Pu SF, Zhuang HX and Ishii DN: Differential spatio-temporal expression of the insulin-like growth factor genes in regenerating sciatic nerve. Brain Res Mol Brain Res. 34:18–28. 1995. View Article : Google Scholar : PubMed/NCBI
23	Butí M, Verdú E, Labrador RO, et al: Influence of physical parameters of nerve chambers on peripheral nerve regeneration and reinnervation. Exp Neurol. 137:26–33. 1996. View Article : Google Scholar : PubMed/NCBI
24	Kou YH, Yin XF, Zhang PX and Jiang BG: Small-gap bridging technology for peripheral nerve injury repair and the new sleeve material. Beijing Da Xue Xue Bao. 43:647–651. 2011.(In Chinese). PubMed/NCBI
25	Zhang ZJ, Gao BQ, Liang CY, Liao ZG, Xu JG and Liu YF: Insulin-like growth factor in the regeneration of facial nerve following injury. Zhongguo Zhongxiyijiehe Er Bi Yanhou Ke Zazhi. 12:7–9. 2004.(In Chinese).
26	Gyula A, Shoushu J, Agnes J, et al: Direct gene transfer and expression into rat heart in vivo. New Biol. 3:711991.PubMed/NCBI
27	Jiao S, Williams P, Berg RK, et al: Direct gene transfer into nonhuman primate myofibers in vivo. Hum Gene Ther. 3:21–33. 1992. View Article : Google Scholar : PubMed/NCBI
28	Sizonenko SV, Sirimanne ES, Williams CE and Gluckman PD: Neuroprotective effects of the N-terminal tripeptide of IGF-1, glycine-proline-glutamate, in the immature rat brain after hypoxic-ischemic injury. Brain Res. 922:42–50. 2001. View Article : Google Scholar : PubMed/NCBI
29	Nagano T, Nakamura M, Nakata K, et al: Effects of substance P and IGF-1 in corneal epithelial barrier function and wound healing in a rat model of neurotrophic keratopathy. Invest Ophthalmol Vis Sci. 44:3810–3815. 2003. View Article : Google Scholar : PubMed/NCBI
30	Zhang SQ, Liu L, Zhang JQ, et al: Expression of exogenous gene at the site of anastomoses of peripheral nerve. Tong Ji Yi Ke Da Xue Xue Bao. 33:455–458. 2004.(In Chinese).