Erythropoietin decreases apoptosis and promotes Schwann cell repair and phagocytosis following nerve crush injury in mice

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

After peripheral nerve trauma, insufficient clearance of phagocytic debris significantly hinders regeneration. Without sufficient myelin clearance, Schwann cells (SCs) undergo increased apoptosis, impairing functional recovery. There is no treatment for crush injury (PNCI). Erythropoietin (EPO) an FDA-approved drug anemia, which may help in the PNCI by transdifferentiating resident SCs into repair (rSCs) and enhancing phagocytosis to facilitate removal cellular debris. For first time, we conducted bulk RNA sequencing on mice with calibrated sciatic injuries (SNCIs) days 3, 5, 7 post-SNCI uncover transcriptomic changes without EPO treatment. We found altered several biological pathways associated genes, particularly those involved cell differentiation, proliferation, phagocytosis, myelination, neurogenesis. validated effects SNCI early (days 3/5) intermediate (day 7) post-SNCI, reduced apoptosis (TUNEL), enhanced SC (c-Jun p75-NTR), proliferation (Ki67), rSCs at sites. This improvement corresponded index (SFI). also confirmed these findings in-vitro . during de-differentiation, marked high c-Jun p75-NTR protein levels, later re-differentiation EGR2 low levels. These occurred under lipopolysaccharide (LPS) stress 24 72h, respectively, compared LPS alone. Under stress, or dead SCs. In conclusion, our support enhance function as a basis its possible use treating trauma.

Language: Английский

Optimizing Peripheral Nerve Regeneration: Surgical Techniques, Biomolecular and Regenerative Strategies—A Narrative Review

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3895 - 3895

Published: April 20, 2025

Peripheral nerve injury disrupts the function of peripheral nervous system, leading to sensory, motor, and autonomic deficits. While nerves possess an intrinsic regenerative capacity, complete sensory motor recovery remains challenging due unpredictable nature healing process, which is influenced by extent injury, age, timely intervention. Recent advances in microsurgical techniques, imaging technologies, a deeper understanding microanatomy have enhanced functional outcomes repair. Nerve initiates complex pathophysiological responses, including Wallerian degeneration, macrophage activation, Schwann cell dedifferentiation, axonal sprouting. Complete disruptions require surgical intervention restore continuity function. Direct repair gold standard for clean transections with minimal gaps. However, cases larger gaps or when direct not feasible, alternatives such as autologous grafting, vascularized grafts, conduits, allografts, transfers may be employed. Autologous grafts provide excellent biocompatibility but are limited donor site morbidity availability. Vascularized used large poorly recipient beds, while conduits serve promising solution smaller utilized neither nor grafting possible, often involving re-routing intact regional play pivotal role regeneration bridging gaps, significant advancements made material composition design. Emerging trends include use 3D bioprinting personalized gene therapy targeted growth factor delivery, nanotechnology nanofiber-based stem therapy. Advancements molecular sciences provided critical insights into cellular biochemical mechanisms underlying repair, therapies that enhance regeneration, remyelination, injuries. This review explores current strategies therapeutic management injuries, highlighting their indications, benefits, limitations, emphasizing need tailored approaches based on severity patient factors.

Language: Английский