Best time window for the use of calcium-modulating agents to improve functional recovery in injured peripheral nerves-An experiment in rats. J Neurosci Res 2017 Sep;95(9):1786-1795
Date
01/05/2017Pubmed ID
28052373DOI
10.1002/jnr.24009Scopus ID
2-s2.0-85007518193 (requires institutional sign-in at Scopus site) 1 CitationAbstract
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.
Author List
Yan Y, Shen FY, Agresti M, Zhang LL, Matloub HS, LoGiudice JA, Havlik R, Li J, Gu YD, Yan JGAuthors
Robert Havlik MD Chair, Professor in the Plastic Surgery department at Medical College of WisconsinJohn A. LoGiudice MD Professor in the Plastic Surgery department at Medical College of Wisconsin
Hani S. Matloub MD Professor in the Plastic Surgery department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsCalcitonin
Calcium
Calcium Channel Blockers
Male
Nerve Crush
Nerve Regeneration
Nifedipine
Peripheral Nerve Injuries
Rats
Rats, Sprague-Dawley
Recovery of Function
