Effect of memantine on the survival of an ischemic random skin flap and the underlying mechanism

Fan, Weijian; Liu, Zhenhua; Chen, Jianpeng; Liu, Shaodong; Chen, Tingxiang; Li, Zhijie; Lin, Dong

doi:10.1016/j.biopha.2021.112163

Cited by 20 publications

(17 citation statements)

References 32 publications

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“…Structural changes including hair follicular and sebaceous gland atrophy, epithelial degeneration, and collagen necrosis are late findings typically not seen before 3 days, but evident at 14 days (Dogan et al, 2021;Tsai et al, 2015). Neovascularization and vessel density are also late findings (5-14 days), with decreased vessel density in IRI compared to ischemia (Fan et al, 2021;Park et al, 2016). H&E staining is most appropriately used during this time period (3-14 days).…”

Section: Resultsmentioning

confidence: 99%

“…In IRI, TUNEL can detect apoptosis as early as 6 h after reperfusion (Yue et al, 2016). VEGF and Cluster of differentiation 31 (CD31), a vascular endothelial cell marker for determining micro‐vessel density, can be used to assess neovascularization after 1–10 and 5–10 days, respectively (Chehelcheraghi et al, 2019; Fan et al, 2021; Khan et al, 2013; Vihanto et al, 2005). Additionally, IHC has the primary advantage of providing subcellular localization and can track transcription factors such as NF‐κB which is normally inactive in the cytoplasm and translocates to the nucleus under stressed conditions to promote pro‐inflammatory cascades (Kang et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…These scoring scales are heterogenous and subjective, which limit direct comparisons among studies. Counting inflammatory cells and micro‐vessels are more objective histological approaches, however the number of evaluated fields and magnification were variable (Fan et al, 2021; Gürsoy et al, 2020; Hasdemir et al, 2015; Turker Ozyigit et al, 2007). The total number of neutrophils or number of vessels can be counted in separate fields and averaged by unit area (mm 2 ) for more consistent reporting.…”

Section: Discussionmentioning

confidence: 99%

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Systematic review of pathologic markers in skin ischemia with and without reperfusion injury in microsurgical reconstruction: Biomarker alterations precede histological structure changes

Khalaf,

Duarte Bateman,

Reyes

et al. 2024

Microsurgery

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BackgroundIschemia and ischemia–reperfusion injury contribute to partial or complete flap necrosis. Traditionally, skin histology has been used to evaluate morphological and structural changes, however histology does not detect early changes. We hypothesize that morphological and structural skin changes in response to ischemia and IRI occur late, and modification of gene and protein expression are the earliest changes in ischemia and IRI.MethodsA systematic review was performed in accordance with PRISMA guidelines. Studies reporting skin histology or gene/protein expression changes following ischemia with or without reperfusion injury published between 2002 and 2022 were included. The primary outcomes were descriptive and semi‐quantitative histological structural changes, leukocyte infiltration, edema, vessel density; secondary outcomes were quantitative gene and protein expression intensity (PCR and western blot). Model type, experimental intervention, ischemia method and duration, reperfusion duration, biopsy location and time point were collected.ResultsOne hundred and one articles were included. Hematoxylin and eosin (H&E) showed inflammatory infiltration in early responses (12–24 h), with structural modifications (3–14 days) and neovascularization (5–14 days) as delayed responses. Immunohistochemistry (IHC) identified angiogenesis (CD31, CD34), apoptosis (TUNEL, caspase‐3, Bax/Bcl‐2), and protein localization (NF‐κB). Gene (PCR) and protein expression (western blot) detected inflammation and apoptosis; endoplasmic reticulum stress/oxidative stress and hypoxia; and neovascularization. The most common markers were TNF‐α, IL‐6 and IL‐1β (inflammation), caspase‐3 (apoptosis), VEGF (neovascularization), and HIF‐1α (hypoxia).ConclusionThere is no consensus or standard for reporting skin injury during ischemia and IRI. H&E histology is most frequently performed but is primarily descriptive and lacks sensitivity for early skin injury. Immunohistochemistry and gene/protein expression reveal immediate and quantitative cellular responses to skin ischemia and IRI. Future research is needed towards a universally‐accepted skin injury scoring system.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Systematic review of pathologic markers in skin ischemia with and without reperfusion injury in microsurgical reconstruction: Biomarker alterations precede histological structure changes

Khalaf,

Duarte Bateman,

Reyes

et al. 2024

Microsurgery

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“…PB2 inhibits LPS‐induced production of inflammatory factors such as tumor necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β), which has anti‐inflammatory effects in acute lung injury (Jiang et al, 2020). Fan et al also discovered that PB2 facilitated diabetic wound healing by regulating OS and angiogenesis (Fan, Liu, Chen, et al, 2021). Moreover, PB2 reduced high glucose‐induced diabetic retinopathy by significantly upregulating Sirt1 expression.…”

Section: Introductionmentioning

confidence: 99%

Procyanidin B2 regulates the Sirt1/Nrf2 signaling pathway to improve random‐pattern skin flap survival

Zhu

et al. 2023

Phytotherapy Research

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Random‐pattern skin flaps have been widely used in the reconstruction of damaged tissues. Ischemia–reperfusion injury occurring in the distal regions of the flap is a common issue, which often leads to flap necrosis and restricts its clinical applications. Procyanidin B2 (PB2), a naturally occurring flavonoid in large quantities in various fruits, has been demonstrated to exhibit several significant pharmacological properties. However, the effect of PB2 on flap viability is not clearly known. Here, using Western blot analysis, immunohistochemistry, and immunofluorescence staining, we observed that PB2 significantly reduced oxidative stress and inflammation and enhanced angiogenesis. Mechanically, we provided evidence for the first time that the beneficial effects of PB2 occur through the activation of the Sirt1/Nrf2 signaling pathway. Moreover, co‐administration of PB2 and EX527, a selective inhibitor of Sirt1, resulted in down‐regulation of the expression of Sirt1, Nrf2, and downstream antioxidants. In summary, our study showed that PB2 might be a novel therapeutic strategy for improving the survival of random‐pattern skin flaps.

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“…Therefore, flap necrosis is highly probable after distal displacement of some flaps due to malnutrition (Deng et al, 2019). Flap survival is also influenced by metabolic factors and the degree of tolerance of the tissue to ischemia and hypoxia (Fan et al, 2021;Huang et al, 2021). Changes in toxic products such as lipid peroxides and reactive oxygen species (ROS) in tissues and blood vessels caused by ischemia-reperfusion injury after flap repair can also lead to flap necrosis (Carroll and Esclamado, 2000;van den Heuvel et al, 2009), so it is important to improve the flap microcirculation, increase angiogenesis, and reduce the damage caused by flap ischemia-reperfusion to improve flap survival.…”

mentioning

confidence: 99%

Therapeutic potential of naringin in improving the survival rate of skin flap: A review

Wang

et al. 2023

Front. Pharmacol.

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Naringin is the main component of Drynaria. Modern pharmacological studies have shown that naringin has a wide range of pharmacological activities, including antioxidant, anti-inflammatory, anti-apoptotic, anti-ulcer, and anti-osteoporosis effects. Its therapeutic effects have been observed in various clinical models, such as atherosclerosis, cardiovascular diseases, diabetes, neurodegenerative diseases, and rheumatic diseases. This review investigates the pharmacological effects of naringin and the associated mechanisms in improving flap survival. This review will also provide a reference for future rational application of naringin, especially in research to improve flap survival.

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Effect of memantine on the survival of an ischemic random skin flap and the underlying mechanism

Cited by 20 publications

References 32 publications

Systematic review of pathologic markers in skin ischemia with and without reperfusion injury in microsurgical reconstruction: Biomarker alterations precede histological structure changes

Systematic review of pathologic markers in skin ischemia with and without reperfusion injury in microsurgical reconstruction: Biomarker alterations precede histological structure changes

Procyanidin B2 regulates the Sirt1/Nrf2 signaling pathway to improve random‐pattern skin flap survival

Therapeutic potential of naringin in improving the survival rate of skin flap: A review

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