scholarly journals Lipin1 Alleviates Autophagy Disorder in Sciatic Nerve and Improves Diabetic Peripheral Neuropathy

2021 ◽  
Author(s):  
Meijian Wang ◽  
Min Xie ◽  
Shuyan Yu ◽  
Pan Shang ◽  
Cong Zhang ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Sciatic Nerve ◽  
Phosphatidic Acid ◽  
Diabetic Peripheral Neuropathy ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Motor Nerve ◽  
Ischemia Reperfusion ◽  
Nerve Tissue ◽  
Conduction Function

Abstract Diabetic peripheral neuropathy (DPN) is a chronic complication of diabetes, and its exact pathogenesis remains unclear. Autophagy plays an important role in neurodegenerative diseases, ischemia–reperfusion injury of nerve tissues, and nerve tissue injury repair. Lipin1 is a phosphatidic acid phosphatase enzyme that converts phosphatidic acid (PA) into diacylglycerol (DAG), a precursor of triacylglycerol and phospholipids which plays an important role in maintaining normal peripheral nerve conduction function. Here, we show that induction of DPN rat model via STZ injection could reduce Lipin1 expression, prevent DAG synthesis, and results in autophagic hyperactivity. Interestingly, these effects increase the apoptosis of Schwann cells and lead to demyelination in sciatic nerve in DPN rats. More importantly, upregulation of lipin1 in the DPN rats ameliorated autophagy disorders and pathological changes of the sciatic nerve, which associated with the increase of the motor nerve conductive velocity (MNCV) in DPN rats. In contrast, lipin1 downregulation exacerbates neuronal abnormalities and facilitates the genesis of DPN phenotypes in rats. In addition, overexpression of lipin1 in RSC96 cells also significantly decreased the autophagic hyperactivity and apoptosis induced by hyperglycemia. These results suggest that lipin1 may exert neuroprotection within the sciatic nerve anomalies and may serve as a potential therapeutic target for the treatment of DPN.

scholarly journals Sensory-Motor Mechanisms Increasing Falls Risk in Diabetic Peripheral Neuropathy

Medicina ◽  
2021 ◽  
Vol 57 (5) ◽  
pp. 457
Author(s):  
Neil D. Reeves ◽  
Giorgio Orlando ◽  
Steven J. Brown
Keyword(s):  
Peripheral Neuropathy ◽  
Diabetic Peripheral Neuropathy ◽  
Motor Nerve ◽  
Step Length ◽  
Falls Prevention ◽  
Motor Deficits ◽  
Falls Risk ◽  
Walking Gait ◽  
Risk Of Falls ◽  
Diabetes Patients

Diabetic peripheral neuropathy (DPN) is associated with peripheral sensory and motor nerve damage that affects up to half of diabetes patients and is an independent risk factor for falls. Clinical implications of DPN-related falls include injury, psychological distress and physical activity curtailment. This review describes how the sensory and motor deficits associated with DPN underpin biomechanical alterations to the pattern of walking (gait), which contribute to balance impairments underpinning falls. Changes to gait with diabetes occur even before the onset of measurable DPN, but changes become much more marked with DPN. Gait impairments with diabetes and DPN include alterations to walking speed, step length, step width and joint ranges of motion. These alterations also impact the rotational forces around joints known as joint moments, which are reduced as part of a natural strategy to lower the muscular demands of gait to compensate for lower strength capacities due to diabetes and DPN. Muscle weakness and atrophy are most striking in patients with DPN, but also present in non-neuropathic diabetes patients, affecting not only distal muscles of the foot and ankle, but also proximal thigh muscles. Insensate feet with DPN cause a delayed neuromuscular response immediately following foot–ground contact during gait and this is a major factor contributing to increased falls risk. Pronounced balance impairments measured in the gait laboratory are only seen in DPN patients and not non-neuropathic diabetes patients. Self-perception of unsteadiness matches gait laboratory measures and can distinguish between patients with and without DPN. Diabetic foot ulcers and their associated risk factors including insensate feet with DPN and offloading devices further increase falls risk. Falls prevention strategies based on sensory and motor mechanisms should target those most at risk of falls with DPN, with further research needed to optimise interventions.

scholarly journals What we need to know about lipid-associated injury in case of renal ischemia-reperfusion

2018 ◽  
Vol 315 (6) ◽  
pp. F1714-F1719 ◽  
Author(s):  
Pauline Erpicum ◽  
Pascal Rowart ◽  
Jean-Olivier Defraigne ◽  
Jean-Marie Krzesinski ◽  
François Jouret
Keyword(s):  
Energy Demand ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Current Knowledge ◽  
Ischemia Reperfusion ◽  
Acid Oxidation ◽  
Metabolic Switch ◽  
Cell Functions ◽  
Associated Injury ◽  
Cortex Area

Renal segmental metabolism is reflected by the complex distribution of the main energy pathways along the nephron, with fatty acid oxidation preferentially used in the cortex area. Ischemia/reperfusion injury (IRI) is due to the restriction of renal blood flow, rapidly leading to a metabolic switch toward anaerobic conditions. Subsequent unbalance between energy demand and oxygen/nutrient delivery compromises kidney cell functions, resulting in a complex inflammatory cascade including the production of reactive oxygen species (ROS). Renal IRI especially involves lipid accumulation. Lipid peroxidation is one of the major events of ROS-associated tissue injury. Here, we briefly review the current knowledge of renal cell lipid metabolism in normal and ischemic conditions. Next, we focus on renal lipid-associated injury, with emphasis on its mechanisms and consequences during the course of IRI. Finally, we discuss preclinical observations aiming at preventing and/or attenuating lipid-associated IRI.

microRNA-223 promotes autophagy to aggravate lung ischemia-reperfusion injury by inhibiting the expression of transcription factor HIF2α

2020 ◽  
Vol 319 (1) ◽  
pp. L1-L10
Author(s):  
Chunlin Ye ◽  
Wanghong Qi ◽  
Shaohua Dai ◽  
Guowen Zou ◽  
Weicheng Liu ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Cell Model ◽  
Ischemia Reperfusion ◽  
Pulmonary Ventilation ◽  
Pulmonary Arteries ◽  
Luciferase Reporter ◽  
Tunel Staining ◽  
Luciferase Reporter Gene ◽  
Gene Assay

Lung ischemia-reperfusion (I/R) injury severely endangers human health, and recent studies have suggested that certain microRNAs (miRNAs) play important roles in this pathological phenomenon. The current study aimed to ascertain the ability of miR-223 to influence lung I/R injury by targeting hypoxia-inducible factor-2α (HIF2α). First, mouse models of lung I/R injury were established: during surgical procedures, pulmonary arteries and veins and unilateral pulmonary portal vessels were blocked and resuming bilateral pulmonary ventilation, followed by restoration of bipulmonary ventilation. In addition, a lung I/R injury cell model was constructed by exposure to hypoxic reoxygenation (H/R) in mouse pulmonary microvascular endothelial cells (PMVECs). Expression of miR-223, HIF2α, and β-catenin in tissues or cells was determined by RT-qPCR and Western blot analysis. Correlation between miR-223 and HIF2α was analyzed by dual luciferase reporter gene assay. Furthermore, lung tissue injury and mouse PMVEC apoptosis was evaluated by hematoxylin and eosin (H&E), TUNEL staining, and flow cytometry. Autophagosomes in cells were detected by light chain 3 immunofluorescence assay. miR-223 was expressed at a high level while HIF2α/β-catenin was downregulated in tissues and cells with lung I/R injury. Furthermore, miR-223 targeted and repressed HIF2α expression to downregulate β-catenin expression. The miR-223/HIF2α/β-catenin axis aggravated H/R injury in mouse PMVECs and lung I/R injury in mice by enhancing autophagy. Taken together, miR-223 inhibits HIF2α to repress β-catenin, thus contributing to autophagy to complicate lung I/R injury. These findings provide a promising therapeutic target for treating lung I/R injury.

scholarly journals Inhibition of leukocyte L-selectin function with a monoclonal antibody attenuates reperfusion injury to the rabbit ear

Blood ◽  
1994 ◽  
Vol 84 (7) ◽  
pp. 2322-2328 ◽  
Author(s):  
D Mihelcic ◽  
B Schleiffenbaum ◽  
TF Tedder ◽  
SR Sharar ◽  
JM Harlan ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Treated Group ◽  
Arterial Blood Flow ◽  
Arterial Blood ◽  
Rabbit Ear ◽  
Adhesive Interactions

Abstract The leukocyte adhesion molecule L-selectin mediates neutrophil adhesive interactions with endothelial cells and is in part responsible for neutrophil rolling. We examined the role of L-selectin in ischemia- reperfusion injury of rabbit ears using a monoclonal antibody (MoAb) directed to a functional epitope of L-selectin. Arterial blood flow to the rabbit ear was occluded for six hours with ambient temperature at 23 degrees C to 24 degrees C. Rabbits were treated at reperfusion with saline (n = 8), the L-selectin function-blocking LAM1–3 MoAb (2 mg/kg), or the nonfunction-blocking LAM1–14 MoAb (2 mg/kg). Tissue injury was determined by measuring edema and necrosis. Edema in the LAM1–3 MoAb- treated group (peak = 25 +/- 4 mL) was significantly less (P < .05) than in saline-treated (peak = 40 +/- 8 mL) and LAM1–14 MoAb-treated (peak = 41 +/- 6 mL) groups. Tissue necrosis at 7 days was not observed in the LAM1–3 MoAb-treated group, whereas significant necrosis (P < .05) was seen in the saline- (8% +/- 3% necrosis) and LAM1–14 MoAb- treated (7% +/- 3% necrosis) group. We conclude that blocking L- selectin ameliorates necrosis and edema after ischemia and reperfusion in the rabbit ear, presumably by blocking neutrophil rolling.

Role of leukocyte plugging and edema in skeletal muscle ischemia-reperfusion injury

1997 ◽  
Vol 273 (2) ◽  
pp. H989-H996 ◽  
Author(s):  
A. G. Harris ◽  
M. Steinbauer ◽  
R. Leiderer ◽  
K. Messmer
Keyword(s):  
Tissue Damage ◽  
Network Flow ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Capillary Density ◽  
Vessel Diameter ◽  
Cell Nuclei ◽  
Dorsal Skinfold Chamber ◽  
Tissue Edema

The purpose of this study was to examine the relationship of increased capillary network resistance due to leukocyte-capillary plugging and tissue edema through macromolecular leakage to tissue injury after ischemia-reperfusion (I/R). After a 3-h complete ischemia in the dorsal skinfold chamber of the awake Syrian hamster, the following parameters were measured: vessel diameter, macromolecular leakage, erythrocyte velocity, adherent leukocytes, rolling leukocytes, freely flowing leukocytes, functional capillary density (FCD), propidium iodide (PI)-positive cell nuclei, and increase in network flow resistance due to leukocyte-capillary plugging. These measurements were made under baseline conditions and after 0.5 and 2 h of reperfusion for I/R alone, I/R with phalloidin (PL) treatment (to block leakage), and I/R with both PL and cytochalasin D (CD) (to block both leakage and plugging). Neither treatment had an effect on the leukocyte adherence or rolling. PL treatment preserved the endothelial barrier, improved FCD, and reduced the amount of PI measured tissue damage. CD treatment eliminated the increase in network resistance due to leukocyte plugging but did not improve FCD or tissue damage. Thus, in this I/R model, macromolecular leakage plays a role in tissue injury, whereas leukocyte plugging does not appear to be an important mechanism.

scholarly journals Enhanced Effect of IL-1β-Activated Adipose-Derived MSCs (ADMSCs) on Repair of Intestinal Ischemia-Reperfusion Injury via COX-2-PGE2 Signaling

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Liu Liu ◽  
Yi Ren He ◽  
Shao Jun Liu ◽  
Lei Hu ◽  
Li Chuang Liang ◽  
...  
Keyword(s):  
Therapeutic Effect ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Suppressive Effect ◽  
Signaling Axis ◽  
Cox 2 ◽  
Underlying Mechanisms ◽  
Intestinal Ischemia Reperfusion

Adipose-derived mesenchymal stem cells (ADMSCs) have been used for treating tissue injury, and preactivation enhances their therapeutic effect. This study is aimed at investigating the therapeutic effect of activated ADMSCs by IL-1β on the intestinal ischaemia-reperfusion (IR) injury and exploring potential mechanisms. ADMSCs were pretreated with IL-1β in vitro, and activation of ADMSCs was assessed by α-SMA and COX-2 expressions and secretary function. Activated ADMSCs was transplanted into IR-injured intestine in a mouse model, and therapeutic effect was evaluated. In addition, to explore underlying mechanisms, COX-2 expression was silenced to investigate its role in activated ADMSCs for treatment of intestinal IR injury. When ADMSCs were pretreated with 50 ng/ml IL-1β for 24 hr, expressions of α-SMA and COX-2 were significantly upregulated, and secretions of PGE2, SDF-1, and VEGF were increased. When COX-2 was silenced, the effect of IL-1β treatment was abolished. Activated ADMSCs with IL-1β significantly suppressed inflammation and apoptosis and enhanced healing of intestinal IR injury in mice, and these effects were impaired by COX-2 silencing. The results of RNA sequencing suggested that compared with the IR injury group activated ADMSCs induced alterations in mRNA expression and suppressed the activation of the NF-κB-P65, MAPK-ERK1/2, and PI3K-AKT pathways induced by intestinal IR injury, whereas silencing COX-2 impaired the suppressive effect of activated ADMSCs on these pathway activations induced by IR injury. These data suggested that IL-1β pretreatment enhanced the therapeutic effect of ADMSCs on intestinal IR injury repairing via activating ADMSC COX-2-PGE2 signaling axis and via suppressing the NF-κB-P65, MAPK-ERK1/2, and PI3K-AKT pathways in the intestinal IR-injured tissue.

scholarly journals Targeting HIF-1α to Prevent Renal Ischemia-Reperfusion Injury: Does It Work?

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Kapil Sethi ◽  
Kenny Rao ◽  
Damien Bolton ◽  
Oneel Patel ◽  
Joseph Ischia
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Arterial Occlusion ◽  
Small Animal ◽  
Kidney Injury ◽  
Renal Ischemia ◽  
Metabolic Adaptation ◽  
Critical Ischemia

Partial nephrectomy (open or minimally invasive) usually requires temporary renal arterial occlusion to limit intraoperative bleeding and improve access to intrarenal structures. This is a time-critical step due to the critical ischemia period of renal tissue. Prolonged renal ischemia may lead to irreversible nephron damage in the remaining tissue and, ultimately, chronic kidney disease. This is potentiated by the incompletely understood ischemia-reperfusion injury (IRI). A key mechanism in IRI prevention appears to be the upregulation of an intracellular transcription protein, Hypoxia-Inducible Factor (HIF). HIF mediates metabolic adaptation, angiogenesis, erythropoiesis, cell growth, survival, and apoptosis. Upregulating HIF-1α via ischemic preconditioning (IPC) or drugs that simulate hypoxia (hypoxia-mimetics) has been investigated as a method to reduce IRI. While many promising chemical agents have been trialed for the prevention of IRI in small animal studies, all have failed in human trials. The aim of this review is to highlight the techniques and drugs that target HIF-1α and ameliorate IRI associated with renal ischemia. Developing a technique or drug that could reduce the risk of acute kidney injury associated with renal IRI would have an immediate worldwide impact on multisystem surgeries that would otherwise risk ischemic tissue injury.

Effect of Ischemia and Reperfusion on Skeletal Muscle Damage

2010 ◽  
Author(s):  
Sandra Loerakker ◽  
Emmy Manders ◽  
Gustav J. Strijkers ◽  
Frank P. T. Baaijens ◽  
Dan L. Bader ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Damage ◽  
Soft Tissues ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Ischemia And Reperfusion ◽  
Skin Damage ◽  
Deep Tissue ◽  
Skeletal Muscle Damage

Sustained mechanical loading of soft tissues covering bony prominences, as experienced by bedridden and wheelchair-bound individuals, may cause skeletal muscle damage. This can result in a condition termed pressure-related deep tissue injury (DTI), a severe kind of pressure ulcer that initiates in deep tissue layers, and progresses towards the skin. Damage pathways leading to DTI can involve ischemia, ischemia/reperfusion injury, impaired lymphatic drainage, and sustained tissue deformation. Recently, we have provided evidence that in a controlled animal model, deformation is the main trigger for damage within a 2h loading period [1,2]. However, ischemia and reperfusion may play a more important role in the damage process during prolonged loading periods.

Sign in / Sign up

Export Citation Format

Share Document