ATP5J regulates microglial activation via mitochondrial dysfunction, exacerbating neuroinflammation in intracerebral hemorrhage DOI Creative Commons

Naixin Ren,

Hutao Zhang,

Tao Li

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 13, 2024

Microglial-mediated neuroinflammation is crucial in the pathophysiological mechanisms of secondary brain injury (SBI) following intracerebral hemorrhage (ICH). Mitochondria are central regulators inflammation, influencing key pathways such as alternative splicing, and play a critical role cell differentiation function. Mitochondrial ATP synthase coupling factor 6 (ATP5J) participates various pathological processes, proliferation, migration, inflammation. However, ATP5J microglial activation post-ICH poorly understood. This study aimed to investigate effects on subsequent ICH elucidate underlying mechanisms. We observed that was upregulated microglia after ICH. AAV9-mediated overexpression worsened neurobehavioral deficits, disrupted blood-brain barrier, increased water content mice. Conversely, knockdown ameliorated these effects. also intensified activation, neuronal apoptosis, inflammatory responses surrounding tissues post-ICH. impaired dynamics reduced proliferation migration sites. used oxyhemoglobin (OxyHb) stimulate BV2 cells model vitro . Further studies showed enhanced OxyHb-induced functional transformation. Mechanistically, silencing reversed dynamin-related protein 1 (Drp1) mitochondrial fission (Fis1) upregulation post-OxyHb induction; overdivision, excessive permeability transition pore opening, reactive oxygen species production; restored normal ridge morphology; partially respiratory electron transport chain activity. further alleviated dysfunction by regulating metabolism. Our results indicate transformation modulating metabolism, thereby positively regulate neuroinflammation. By inhibiting ATP5J, SBI could be prevented. Therefore, candidate for molecular therapeutic target exploration alleviate

Language: Английский

Neuroregulation during Bone Formation and Regeneration: Mechanisms and Strategies DOI

Xiangrong Zhao,

Meilin Yao, Yuyi Wang

et al.

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

The skeleton is highly innervated by numerous nerve fibers. These fibers, in addition to transmitting information within the bone and mediating sensations, play a crucial role regulating tissue formation regeneration. Traditional engineering (BTE) often fails achieve satisfactory outcomes when dealing with large-scale defects, which frequently related lack of effective reconstruction neurovascular network. In recent years, increasing research has revealed critical nerves metabolism. Nerve fibers regulate cells through neurotransmitters, neuropeptides, peripheral glial cells. Furthermore, also coordinate vascular immune systems jointly construct microenvironment favorable for As signaling driver formation, neuroregulation spans entire process physiological activities from embryonic postmaturity remodeling repair. However, there currently comprehensive summaries these regulatory mechanisms. Therefore, this review sketches out function during Then, we elaborate on mechanisms coupling neuromodulation immunity. Finally, discuss several novel strategies neuro-bone (NBTE) based bone, focusing coordinated regeneration tissue.

Language: Английский

Citations

1
Strategies for promoting neurovascularization in bone regeneration DOI Creative Commons
Xinling Li, Yuqing Zhao, Miao Li

et al.

Military Medical Research, Journal Year: 2025, Volume and Issue: 12(1)

Published: March 3, 2025

Abstract Bone tissue relies on the intricate interplay between blood vessels and nerve fibers, both are essential for many physiological pathological processes of skeletal system. Blood provide necessary oxygen nutrients to bone tissues, remove metabolic waste. Concomitantly, fibers precede during growth, promote vascularization, influence cells by secreting neurotransmitters stimulate osteogenesis. Despite critical roles components, current biomaterials generally focus enhancing intraosseous vessel repair, while often neglecting contribution nerves. Understanding distribution main functions in is crucial developing effective engineering. This review first explores anatomy highlighting their vital embryonic development, metabolism, repair. It covers innovative regeneration strategies directed at accelerating intrabony neurovascular system over past 10 years. The issues covered included material properties (stiffness, surface topography, pore structures, conductivity, piezoelectricity) acellular biological factors [neurotrophins, peptides, ribonucleic acids (RNAs), inorganic ions, exosomes]. Major challenges encountered neurovascularized materials clinical translation have also been highlighted. Furthermore, discusses future research directions potential developments aimed producing repair that more accurately mimic natural healing tissue. will serve as a valuable reference researchers clinicians novel into practice. By bridging gap experimental practical application, these advancements transform treatment defects significantly improve quality life patients with bone-related conditions.

Language: Английский

Citations

1
The application of stem cells and exosomes in promoting nerve conduits for peripheral nerve repair DOI Creative Commons
Mengen Li, Yue Tang, Cheng‐Kai Zhou

et al.

Biomaterials Research, Journal Year: 2025, Volume and Issue: 29

Published: Jan. 1, 2025

The repair of peripheral nerve injury (PNI) presents a multifaceted and protracted challenge, with current therapeutic approaches failing to achieve optimal outcomes, thereby not satisfying the considerable clinical demand. advent tissue engineering has led growing body experimental evidence indicating that synergistic application conduits, which provide structural guidance, alongside biological signals derived from exosomes stem cells, yields superior results for PNI compared isolated interventions. This combined approach holds great promise application. In this review, we present latest advancements in treatment through integration cells or conduits. We have addressed inadequate efficiency conjunction conduits 3 perspectives: enhancing exosomes, improving incorporating physical stimulation.

Language: Английский

Citations

0
The Role of Endothelial Cell Glycolysis in Schwann Cells and Peripheral Nerve Injury Repair: A Novel and Important Research Area DOI

Li‐Xin Huang,

Tao Sun,

Jun Sun

et al.

Neurochemical Research, Journal Year: 2025, Volume and Issue: 50(2)

Published: March 18, 2025

Language: Английский

Citations

0
Ultrasound‐Driven Innervated Bone Regeneration in Additively Manufactured Degradable Metallic Scaffolds DOI Open Access

Wencheng Song,

Danlei Zhao,

Jiajia Wang

et al.

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

Abstract Bone tissues are densely innervated by nerve fibers throughout the periosteum and mineralized bone. The impairment of bone regeneration is a critical factor contributing to challenges in osteoporotic remodeling repair. Herein, an “ultrasound‐driven regeneration” strategy proposed additively manufactured degradable Zn‐Cu scaffolds. vitro investigations with RSC96 cells elucidated synergistic promotion low‐intensity pulsed ultrasound (LIPUS) metal cations on Schwann cell proliferation exosome secretion. Notably, these cell‐derived exosomes, once internalized neighboring marrow stromal (BMSCs), significantly enhanced their migration, osteogenic differentiation, extracellular matrix deposition, indicating potent mechanism for regeneration. Furthermore, vivo evaluation validated that LIPUS stimulation activated S100β‐positive facilitated peripheral within cranial defects, leading accelerated healing rats implantation over 2‐ 6‐week recovery periods. This work provides focusing activation enhancement paracrine effect, especially secretion, which further recruited surrounding BMSCs promoted differentiation. study holds considerable promise clinical applications translation treatment defects.

Language: Английский

Citations

0
Molecular and Cellular Mechanisms Underlying Peripheral Nerve Injury-Induced Cellular Ecological Shifts: Implications for Neuroregeneration DOI Creative Commons
Li‐Da Wu,

Jinglan He,

Na Shen

et al.

IBRO Neuroscience Reports, Journal Year: 2024, Volume and Issue: 18, P. 120 - 129

Published: Dec. 28, 2024

The peripheral nervous system is a complex ecological network, and its injury triggers series of fine-grained intercellular regulations that play crucial role in the repair process. sophisticated initiates cascade intricate regulatory processes are instrumental Despite advent microsurgical techniques, nerve injuries frequently proves inadequate, resulting adverse effects on patients' quality life. Accordingly, continued pursuit more efficacious treatments paramount importance. In this paper, review relevant literature from recent years was conducted to identify key cell types involved after injury. These included Schwann cells, macrophages, neutrophils, endothelial fibroblasts. depth. This paper analyses phenotypic changes these cells injury, factors affecting changes, how they coordinate with neurons other types. addition, it explores potential mechanisms mediate behaviour cells. Understanding interactions between their mutual regulation great significance for discovery new neuroregenerative identification therapeutic targets.

Language: Английский

Citations

2
Therapeutic effect of exosomes derived from SCs in the repair of peripheral nerve injury DOI
Jialing Wang, Qiming Huang,

Dong-xia Hu

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 357, P. 123086 - 123086

Published: Sept. 30, 2024

Language: Английский

Citations

1
ATP5J regulates microglial activation via mitochondrial dysfunction, exacerbating neuroinflammation in intracerebral hemorrhage DOI Creative Commons

Naixin Ren,

Hutao Zhang,

Tao Li

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 13, 2024

Microglial-mediated neuroinflammation is crucial in the pathophysiological mechanisms of secondary brain injury (SBI) following intracerebral hemorrhage (ICH). Mitochondria are central regulators inflammation, influencing key pathways such as alternative splicing, and play a critical role cell differentiation function. Mitochondrial ATP synthase coupling factor 6 (ATP5J) participates various pathological processes, proliferation, migration, inflammation. However, ATP5J microglial activation post-ICH poorly understood. This study aimed to investigate effects on subsequent ICH elucidate underlying mechanisms. We observed that was upregulated microglia after ICH. AAV9-mediated overexpression worsened neurobehavioral deficits, disrupted blood-brain barrier, increased water content mice. Conversely, knockdown ameliorated these effects. also intensified activation, neuronal apoptosis, inflammatory responses surrounding tissues post-ICH. impaired dynamics reduced proliferation migration sites. used oxyhemoglobin (OxyHb) stimulate BV2 cells model vitro . Further studies showed enhanced OxyHb-induced functional transformation. Mechanistically, silencing reversed dynamin-related protein 1 (Drp1) mitochondrial fission (Fis1) upregulation post-OxyHb induction; overdivision, excessive permeability transition pore opening, reactive oxygen species production; restored normal ridge morphology; partially respiratory electron transport chain activity. further alleviated dysfunction by regulating metabolism. Our results indicate transformation modulating metabolism, thereby positively regulate neuroinflammation. By inhibiting ATP5J, SBI could be prevented. Therefore, candidate for molecular therapeutic target exploration alleviate

Language: Английский

Citations

1