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Carnosine improves functional recovery and structural regeneration after sciatic nerve crush injury in rats.
Life Sci 2018; 215:22-30LS

Abstract

AIMS

Peripheral nerve injury represents a substantial clinical problem with insufficient or unsatisfactory treatment options. Current researches have extensively focused on the new approaches for the treatment of peripheral nerve injuries. Carnosine is a naturally occurring pleotropic dipeptide and has many biological functions such as antioxidant property. In the present study, we examined the regenerative ability of carnosine after sciatic nerve crush injury using behavioral, biochemical, histological and ultrastructural evaluations.

MATERIALS AND METHODS

Seventy-two rats were divided into six groups including control, sham, crush and carnosine (10, 20 and 40 mg/kg) groups. Crush injury in left sciatic nerve was induced by a small haemostatic forceps. Carnosine was administered for 15 consecutive days after induction of crush injury. Sciatic functional index (SFI) was recorded weekly. Histopathological and ultrastructural evaluations were made using light and electron microscopes, respectively. Sciatic nerve tissue malondialdehyde (MDA), superoxide dismutase (SOD) and tumor necrosis factor-alpha (TNF-α) levels were measured. Gastrocnemius muscle weight was determined.

KEY FINDINGS

Carnosine at the doses of 20 and 40 mg/kg accelerated SFI recovery. Wallerian degeneration severity and myelinated fibers density, myelin sheath thickness and diameter as well as ultrastructural changes of myelinated axons were improved. It also recovered nerve tissue biochemical (MDA, SOD and TNF-α) changes induced by crush injury. Muscle weight ratio was reached to near normal values. Our results suggest a regenerative effect of carnosine. Inhibition of oxidative stress and inflammatory pathways, along with provocation of myelination and prevention of muscular atrophy might be involved in this effect of carnosine.

SIGNIFICANCE

Carnosine treatment might be considered as a therapeutic agent for peripheral nerve regeneration and its functional recovery.

Authors+Show Affiliations

Division of Pathology, Department of Pathobiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.Division of Pathology, Department of Pathobiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran. Electronic address: aa.farshid@urmia.ac.ir.Division of Physiology, Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.Division of Biochemistry, Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.Division of Physiology, Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.Division of Pathology, Department of Basic Sciences, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30391465

Citation

Mirzakhani, Navideh, et al. "Carnosine Improves Functional Recovery and Structural Regeneration After Sciatic Nerve Crush Injury in Rats." Life Sciences, vol. 215, 2018, pp. 22-30.
Mirzakhani N, Farshid AA, Tamaddonfard E, et al. Carnosine improves functional recovery and structural regeneration after sciatic nerve crush injury in rats. Life Sci. 2018;215:22-30.
Mirzakhani, N., Farshid, A. A., Tamaddonfard, E., Imani, M., Erfanparast, A., & Noroozinia, F. (2018). Carnosine improves functional recovery and structural regeneration after sciatic nerve crush injury in rats. Life Sciences, 215, pp. 22-30. doi:10.1016/j.lfs.2018.10.043.
Mirzakhani N, et al. Carnosine Improves Functional Recovery and Structural Regeneration After Sciatic Nerve Crush Injury in Rats. Life Sci. 2018 Dec 15;215:22-30. PubMed PMID: 30391465.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Carnosine improves functional recovery and structural regeneration after sciatic nerve crush injury in rats. AU - Mirzakhani,Navideh, AU - Farshid,Amir Abbas, AU - Tamaddonfard,Esmaeal, AU - Imani,Mehdi, AU - Erfanparast,Amir, AU - Noroozinia,Farahnaz, Y1 - 2018/11/01/ PY - 2018/08/20/received PY - 2018/10/20/revised PY - 2018/10/21/accepted PY - 2018/11/6/pubmed PY - 2018/12/12/medline PY - 2018/11/5/entrez KW - Carnosine KW - Carnosine (Pubchem CID: 439224) KW - Chloroform (Pubchem CID: 6212) KW - Ethanol (Pubchem CID: 702) KW - Formaldehyde (Pubchem CID: 712) KW - Functional recovery KW - Lead citrate (Pubchem CID: 159739) KW - Nitrobluetetrazolium (PubChem CID: 9282) KW - Normal saline (PubChem: 5234) KW - Osmium tetroxide (Pubchem CID: 30318) KW - Oxidative stress KW - Rats KW - Regeneration KW - Sciatic nerve crush KW - Sodium dodecyl sulphate (Pubchem CID: 3423265) KW - Thiobarbituric acid (Pubchem CID: 2723628) KW - Uranyl acetate (Pubchem CID: 10915) SP - 22 EP - 30 JF - Life sciences JO - Life Sci. VL - 215 N2 - AIMS: Peripheral nerve injury represents a substantial clinical problem with insufficient or unsatisfactory treatment options. Current researches have extensively focused on the new approaches for the treatment of peripheral nerve injuries. Carnosine is a naturally occurring pleotropic dipeptide and has many biological functions such as antioxidant property. In the present study, we examined the regenerative ability of carnosine after sciatic nerve crush injury using behavioral, biochemical, histological and ultrastructural evaluations. MATERIALS AND METHODS: Seventy-two rats were divided into six groups including control, sham, crush and carnosine (10, 20 and 40 mg/kg) groups. Crush injury in left sciatic nerve was induced by a small haemostatic forceps. Carnosine was administered for 15 consecutive days after induction of crush injury. Sciatic functional index (SFI) was recorded weekly. Histopathological and ultrastructural evaluations were made using light and electron microscopes, respectively. Sciatic nerve tissue malondialdehyde (MDA), superoxide dismutase (SOD) and tumor necrosis factor-alpha (TNF-α) levels were measured. Gastrocnemius muscle weight was determined. KEY FINDINGS: Carnosine at the doses of 20 and 40 mg/kg accelerated SFI recovery. Wallerian degeneration severity and myelinated fibers density, myelin sheath thickness and diameter as well as ultrastructural changes of myelinated axons were improved. It also recovered nerve tissue biochemical (MDA, SOD and TNF-α) changes induced by crush injury. Muscle weight ratio was reached to near normal values. Our results suggest a regenerative effect of carnosine. Inhibition of oxidative stress and inflammatory pathways, along with provocation of myelination and prevention of muscular atrophy might be involved in this effect of carnosine. SIGNIFICANCE: Carnosine treatment might be considered as a therapeutic agent for peripheral nerve regeneration and its functional recovery. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/30391465/Carnosine_improves_functional_recovery_and_structural_regeneration_after_sciatic_nerve_crush_injury_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(18)30668-4 DB - PRIME DP - Unbound Medicine ER -