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Administration of CoCl2 Improves Functional Recovery in a Rat Model of Sciatic Nerve Transection Injury
Article Number: SIS594812AI211222
21st December, 2022
Author(s):
Shuai An, Meng Zhou, Zheng Li, Mingli Feng, Guanglei Cao, Shibao Lu, Limin Liu
Abstract:
Peripheral nerve injury is known to activate the hypoxia-inducible factor-1α (HIF-1α) pathway as
one of pro-regenerative transcriptional programs, which could stimulate multiple injury-induced
gene expression and contribute to axon regeneration and functional recovery. However, the role of
HIF-1α in peripheral nerve regeneration remains to be fully elucidated. In this study, rats were
divided into three groups and treated with sham surgery, surgery with cobalt chloride (CoCl2) and
surgery with saline, respectively. Sciatic functional index, morphologic evaluations of muscle fibers,
and never conduction velocity were performed to measure the functional recovery at 12 weeks
postoperatively. In addition, the effects of CoCl2 on the expression of HIF-1α, glial cell line-derived
neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF) and nerve growth factor
(NGF) were determined at mRNA levels; as well as HIF-1α, the dual leucine zipper kinase (DLK),
the c-Jun N-terminal kinase (JNK), phosphorylated JNK (p-JNK), BDNF and NGF were measured at
protein level at 4 weeks postoperatively. Systemic administration of CoCl2 (15 mg/kg/day
intraperitoneally) significantly promoted functional recovery of rats with sciatic nerve transection
injury. This study demonstrated in rats treated with CoCl2, the expression of HIF-1α, GDNF, BDNF
and NGF was significantly increased at mRNA level, while HIF-1α, DLK, p-JNK, BDNF and NGF was
significantly increased at protein level.