Neurogenic Factors in the Impaired Healing of Diabetic Foot Ulcers

Gałkowska, Hanna; Olszewski, Waldemar L.; Wojewódzka, Urszula; Rosiński, Grzegorz; Karnafel, Waldemar

doi:10.1016/j.jss.2006.02.006

Cited by 53 publications

(46 citation statements)

References 32 publications

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“…Reduced SP and NGF positive nerve fibres are observed in diabetic patients and rats (101,102); as well as reduced NGF and SP levels in the skin and serum (102,103). This could also account for the decrease in angiogenesis seen in this sub-group of patients (104). NPY levels in diabetic skin are reduced (105).…”

Section: Diabetes Mellitusmentioning

confidence: 99%

The Role of Neuromediators and Innervation in Cutaneous Wound Healing

Ashrafi¹,

Baguneid²,

Bayat³

2016

Acta Derm Venerol

100

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The skin is densely innervated with an intricate network of cutaneous nerves, neuromediators and specific receptors which influence a variety of physiological and disease processes. There is emerging evidence that cutaneous innervation may play an important role in mediating wound healing. This review aims to comprehensively examine the evidence that signifies the role of innervation during the overlapping stages of cutaneous wound healing. Numerous neuropeptides that are secreted by the sensory and autonomic nerve fibres play an essential part during the distinct phases of wound healing. Delayed wound healing in diabetes and fetal cutaneous regeneration following wounding further highlights the pivotal role skin innervation and its associated neuromediators play in wound healing. Understanding the mechanisms via which cutaneous innervation modulates wound healing in both the adult and fetus will provide opportunities to develop therapeutic devices which could manipulate skin innervation to aid wound healing.

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Section: Diabetes Mellitusmentioning

confidence: 99%

The Role of Neuromediators and Innervation in Cutaneous Wound Healing

Ashrafi¹,

Baguneid²,

Bayat³

2016

Acta Derm Venerol

100

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“…Interestingly, a reduction in sensory nerve fibers was documented in noninjured skin of patients with diabetes. 34 Furthermore, it was reported that in patients with diabetes as well as in animal models of diabetes diminished levels of systemic NGF can be measured. 6,7 In wounded epithelium of diabetic C57BL/6J-m+ Leprdb mice, diminished or absent NGF immunoreactivity was found as compared to nondiabetic controls.…”

Section: Discussionmentioning

confidence: 99%

Paracrine Loop of Keratinocyte Proliferation and Directed Neuritic Outgrowth in a Neuroepithelial Coculture

Radtke¹,

Rennekampff²,

Reimers³

et al. 2013

Annals of Plastic Surgery

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In the absence of skin innervation, wound healing is delayed and chronic nonhealing wounds may occur. Keratinocytes produce neurotrophic factors, such as nerve growth factor (NGF), which has been suggested to attract primary cutaneous afferent axons and exert mitogenic effects on keratinocytes. The present study was performed to examine the interaction of primary human keratinocytes (hKTs) and rat cutaneous primary afferent dorsal root ganglion (DRG) neurons with regard to neuritic outgrowth and keratinocyte proliferation. Neuritic outgrowth was assessed with neurofilament immunostaining where cell bodies and fine neuritic processes were identified. Neuritic outgrowth of neurons alone in culture is spatially random and radial. Neurites in cocultures of DRG neurons insinuated between the hKTs and grew to "clumps" of hKTs within the cultures. Immunostaining with anti-NGF antibody indicates that hKTs expressed the neurotrophin NGF. Proliferation of keratinocytes was significantly enhanced in coculture with DRG and hKT, and NGF levels were increased as compared to DRG or hKT culture alone. These results indicate a dynamic interaction between DRG neurons and hKTs whereby the DRG neurons issue neurites in association with hKTs and the hKTs up-regulate NGF and increase their proliferation rate. These findings support the hypothesis that nerve-skin interactions play a significant role in wound healing.

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“…Diabetes, peripheral vascular disease, immune deficiency (or suppression), and advanced aged are routinely associated with such alterations. [23][24][25] Diabetes markedly reduces the reaction of HPA axis to hypoglycemia, as suggested by lower than expected increases in adrenocorticotropic hormone (ACTH), corticosterone, and epinephrine. 26 Further, foot ulcers in diabetic patients demonstrate a lack of substance P + nerve endings and a reduced distribution of calcitoningene-related peptide + nerves in the skin.…”

Section: Introductionmentioning

confidence: 99%

“…26 Further, foot ulcers in diabetic patients demonstrate a lack of substance P + nerve endings and a reduced distribution of calcitoningene-related peptide + nerves in the skin. 24 Advanced age also significantly affects the body's response to stress. For example, the heightened hypothalamic response to an acute psychosocial stressor observed in young men notably decreased with age.…”

Section: Introductionmentioning

confidence: 99%