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Nerve growth factor accelerates wound healing in diabetic mice.
Wound Repair Regen 2004 Jan-Feb; 12(1):44-52WR

Abstract

Patients with diabetic neuropathy have reduced numbers of cutaneous nerves, which may contribute to an increased incidence of nonhealing wounds. Nerve growth factor (NGF) has been reported to augment wound closure. We hypothesized that topical 2.5S NGF, a biologically active subunit of the NGF polymer, would accelerate wound repair, augment nerve regeneration, and increase inflammation in excisional wounds in diabetic mice. A full-thickness 6-mm punch biopsy wound was created on the dorsum of C57BL/6J-m+ Leprdb mice (db/db) and heterozygous (db/-) littermates and treated daily with normal saline or 2.5S NGF (1 microg/day or 10 microg/day) on post-injury days 0-6. Time to closure, wound epithelialization, and degree of inflammation were compared using a Student's t-test. Color subtractive-computer-assisted image analysis was used to quantify immunolocalized nerves in wounds. Non-overlapping (20x) digital images of the wound were analyzed for nerve profile counts, area density (number of protein gene product 9.5 positive profiles per unit dermal area) and area fraction (protein gene product 9.5 positive area per unit dermal area). Healing times in db/db mice decreased from 30 days in normal saline-treated mice to 26 days in mice treated with 1 microg/day NGF (p<0.05) and 24 days in mice treated with 10 microg/day NGF (p<0.02). A similar trend in db/- mice was not significant. NGF treatment augmented epithelialization in the db/db mice (p<0.05). Histological evaluation of inflammation in healed wounds showed no statistical difference between treatment groups. Total nerve number, area density, and area fraction were increased in NGF-treated wounds at 14, 21, and 35 days (p<0.05). The 2.5 NGF subunit may improve wound closure kinetics by promoting epithelialization and nerve regeneration. Further studies to determine the role of nerves in wound repair are warranted.

Authors+Show Affiliations

Department of Surgery, University of Washington, Seattle, Washington, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Evaluation Studies
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14974964

Citation

Muangman, Pornprom, et al. "Nerve Growth Factor Accelerates Wound Healing in Diabetic Mice." Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society, vol. 12, no. 1, 2004, pp. 44-52.
Muangman P, Muffley LA, Anthony JP, et al. Nerve growth factor accelerates wound healing in diabetic mice. Wound Repair Regen. 2004;12(1):44-52.
Muangman, P., Muffley, L. A., Anthony, J. P., Spenny, M. L., Underwood, R. A., Olerud, J. E., & Gibran, N. S. (2004). Nerve growth factor accelerates wound healing in diabetic mice. Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society, 12(1), pp. 44-52.
Muangman P, et al. Nerve Growth Factor Accelerates Wound Healing in Diabetic Mice. Wound Repair Regen. 2004;12(1):44-52. PubMed PMID: 14974964.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nerve growth factor accelerates wound healing in diabetic mice. AU - Muangman,Pornprom, AU - Muffley,Lara A, AU - Anthony,Joanne P, AU - Spenny,Michelle L, AU - Underwood,Robert A, AU - Olerud,John E, AU - Gibran,Nicole S, PY - 2004/2/21/pubmed PY - 2004/6/23/medline PY - 2004/2/21/entrez SP - 44 EP - 52 JF - Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society JO - Wound Repair Regen VL - 12 IS - 1 N2 - Patients with diabetic neuropathy have reduced numbers of cutaneous nerves, which may contribute to an increased incidence of nonhealing wounds. Nerve growth factor (NGF) has been reported to augment wound closure. We hypothesized that topical 2.5S NGF, a biologically active subunit of the NGF polymer, would accelerate wound repair, augment nerve regeneration, and increase inflammation in excisional wounds in diabetic mice. A full-thickness 6-mm punch biopsy wound was created on the dorsum of C57BL/6J-m+ Leprdb mice (db/db) and heterozygous (db/-) littermates and treated daily with normal saline or 2.5S NGF (1 microg/day or 10 microg/day) on post-injury days 0-6. Time to closure, wound epithelialization, and degree of inflammation were compared using a Student's t-test. Color subtractive-computer-assisted image analysis was used to quantify immunolocalized nerves in wounds. Non-overlapping (20x) digital images of the wound were analyzed for nerve profile counts, area density (number of protein gene product 9.5 positive profiles per unit dermal area) and area fraction (protein gene product 9.5 positive area per unit dermal area). Healing times in db/db mice decreased from 30 days in normal saline-treated mice to 26 days in mice treated with 1 microg/day NGF (p<0.05) and 24 days in mice treated with 10 microg/day NGF (p<0.02). A similar trend in db/- mice was not significant. NGF treatment augmented epithelialization in the db/db mice (p<0.05). Histological evaluation of inflammation in healed wounds showed no statistical difference between treatment groups. Total nerve number, area density, and area fraction were increased in NGF-treated wounds at 14, 21, and 35 days (p<0.05). The 2.5 NGF subunit may improve wound closure kinetics by promoting epithelialization and nerve regeneration. Further studies to determine the role of nerves in wound repair are warranted. SN - 1067-1927 UR - https://www.unboundmedicine.com/medline/citation/14974964/Nerve_growth_factor_accelerates_wound_healing_in_diabetic_mice_ L2 - https://doi.org/10.1111/j.1067-1927.2004.012110.x DB - PRIME DP - Unbound Medicine ER -