Inhibition of C5aR1 as a promising approach to treat taxane-induced neuropathy DOI Creative Commons
Claudia Cristiano, Cristina Giorgio,

P. Cocchiaro

et al.

Cytokine, Journal Year: 2023, Volume and Issue: 171, P. 156370 - 156370

Published: Sept. 16, 2023

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of several antitumor agents resulting in progressive and often irreversible damage nerves. In addition to their known anticancer effects, taxanes, including paclitaxel, can also induce by activating microglia astrocytes, which release pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin 1-beta (IL-1β), chemokine (C-C motif) ligand 2 (CCL-2). All these events contribute the maintenance neuropathic or inflammatory response. Complement component 5a (C5a)/C5a receptor 1 (C5aR1) signaling was very recently shown play crucial role paclitaxel-induced neuropathy. Our recent findings highlighted that taxanes have previously unreported property binding C5aR1, C5aR1 inhibition DF3966A effective preventing (PIPN) animal models. Here, we investigated if maintains efficacy reducing PIPN therapeutic setting. Furthermore, characterized activation paclitaxel CIPN-associated nod-like (NLR) family pyrin domain containing 3 (NLRP3) inflammasome. results clearly show administration inhibitor strongly reduced cold mechanical allodynia mice when given both during onset well established. found be key event induction factors spinal cord, TNF-α, ionized calcium-binding adapter molecule (Iba-1), glial fibrillary acidic protein (GFAP). addition, significantly mitigated inflammation inflammasome IL-1β NLRP3 expression at sciatic dorsal root ganglia level, confirming involvement PIPN. Moreover, upregulation treatment central nervous system. Lastly, antinociceptive confirmed an vitro model sensory neurons focused on channels usually activated upon conclusion, proposed option with potential exert long-term protective PIPN-associated pain inflammation.

Language: Английский

Pharmacological effects of salidroside on central nervous system diseases DOI Open Access
Meihua Jin, Chun Wang, Yifeng Xu

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 156, P. 113746 - 113746

Published: Oct. 10, 2022

Language: Английский

Citations

40
Role of NLRP3 Inflammasome in Post-Spinal-Cord-Injury Anxiety and Depression: Molecular Mechanisms and Therapeutic Implications DOI
Tahmineh Mokhtari, Kadir Uludağ

ACS Chemical Neuroscience, Journal Year: 2023, Volume and Issue: 15(1), P. 56 - 70

Published: Dec. 18, 2023

The majority of research on the long-term effects spinal cord injury (SCI) has primarily focused neuropathic pain (NP), psychological issues, and sensorimotor impairments. Among SCI patients, mood disorders, such as anxiety depression, have been extensively studied. It found that chronic stress NP negative consequences reduce quality life for individuals living with SCI. Our review examined both human experimental evidence to explore connection between changes following inflammatory pathways, a specific focus NLRP3 inflammasome signaling. We observed increased proinflammatory factors in blood, well brain tissues models. plays crucial role various diseases by controlling release molecules like interleukin 1β (IL-1β) IL-18. Dysregulation key regions associated processing, prefrontal cortex hippocampus, contributes development disorders In this review, we summarized recent expression regulation components related signaling Finally, discussed potential therapeutic approaches target regulate cytokines way treat

Language: Английский

Citations

24
Remodeling of the Intra‐Conduit Inflammatory Microenvironment to Improve Peripheral Nerve Regeneration with a Neuromechanical Matching Protein‐Based Conduit DOI Creative Commons
Jia‐Yi Wang,

Ya Yuan,

John H. Zhang

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(17)

Published: March 2, 2024

Abstract Peripheral nerve injury (PNI) remains a challenging area in regenerative medicine. Nerve guide conduit (NGC) transplantation is common treatment for PNI, but the prognosis of NGC unsatisfactory due to 1) neuromechanical unmatching and 2) intra‐conduit inflammatory microenvironment (IME) resulting from Schwann cell pyroptosis inflammatory‐polarized macrophages. A neuromechanically matched composed regenerated silk fibroin (RSF) loaded with poly(3,4‐ethylenedioxythiophene): poly(styrene sulfonate) (P:P) dimethyl fumarate (DMF) are designed, which exhibits elastic modulus (25.1 ± 3.5 MPa) peripheral highest 80% elongation at break, better than most protein‐based conduits. Moreover, can gradually regulate IME by releasing DMF monitoring sciatic movements via piezoresistive sensing. The combination electrical stimulation modulates support PNI regeneration synergistically inhibiting reducing factor release, shifting macrophage polarization M1 phenotype tissue M2 functional recovery neurons. In rat crush model, promoted remyelination structural regeneration. Generally, DMF/RSF/P:P provides new potential therapeutic approach promote repair future clinical treatments.

Language: Английский

Citations

16
Inflammation in the Peripheral Nervous System after Injury DOI Creative Commons

Dandan Gu,

Yiming Xia,

Zihan Ding

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(6), P. 1256 - 1256

Published: June 5, 2024

Nerve injury is a common condition that occurs as result of trauma, iatrogenic injury, or long-lasting stimulation. Unlike the central nervous system (CNS), peripheral (PNS) has strong capacity for self-repair and regeneration. Peripheral nerve results in degeneration distal axons myelin sheaths. Macrophages Schwann cells (SCs) can phagocytose damaged cells. Wallerian (WD) makes whole axon structure degenerate, creating favorable regenerative environment new axons. After macrophages, neutrophils other are mobilized recruited to site necrotic debris. Pro-inflammatory anti-inflammatory factors involved inflammatory response provide microenvironment regeneration regulate effects inflammation on body through relevant signaling pathways. Previously, was thought be detrimental body, but further research shown appropriate promotes regeneration, formation. On contrary, excessive cause tissue damage pathological changes, even lead neurological diseases. Therefore, after various interact with cytokines chemokines promote repair by inhibiting negative harnessing positive specific ways at times. Understanding interaction between neuroinflammation provides several therapeutic ideas improve

Language: Английский

Citations

15
Implication of lncRNA MSTRG.81401 in Hippocampal Pyroptosis Induced by P2X7 Receptor in Type 2 Diabetic Rats with Neuropathic Pain Combined with Depression DOI Open Access
Ting Zhan, Shanshan Tang,

Junpei Du

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1186 - 1186

Published: Jan. 18, 2024

Major depressive disorder (MDD) is a common complication of diabetes and often observed alongside diabetic neuropathic pain (DNP) as comorbidity in patients. Long non-coding RNA (lncRNA) plays an important role various pathophysiological processes. The P2X7 receptor responsible for triggering inflammatory responses, such pyroptosis, linked to depression. aim this study was investigate the effect lncRNA MSTRG.81401 on hippocampal pyroptosis induced by rats with DNP combined MDD (DNP + MDD). Our results showed that expression significantly elevated hippocampus compared control group. Following administration shRNA targeting MSTRG.81401, notable elevation mechanical thermal thresholds comorbid MDD. Additionally, significant improvements depression-like behaviors were evident open-field test (OFT), sucrose preference (SPT), forced swim (FST). In rats, levels mRNA protein observed, along increased co-expression astrocytic marker glial fibrillary acidic (GFAP). Meanwhile, heightened NOD-like 3 (NLRP3), apoptosis-associated speck-like (ASC), pyroptosis-related Gasdermin D (GSDMD), caspase-1, IL-1β, IL-18, TNF-α detected, addition serum IL-18 TNF-α. After treatment above abnormal changes indicators inflammation improved. Therefore, our demonstrates can alleviate associated inhibiting receptor-mediated pathway pro-inflammatory responses. This suggests P2X7R/NLRP3/caspase-1 implicated scenario may serve potential target management diabetes.

Language: Английский

Citations

11
Stigmasterol alleviates neuropathic pain by reducing Schwann cell‐macrophage cascade in DRG by modulating IL‐34/CSF1R DOI Creative Commons
Wai‐mei Si, Zhenni Chen,

Jing Bei

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(4)

Published: April 1, 2024

Abstract Aims This study aimed to investigate the potential therapeutic applications of stigmasterol for treating neuropathic pain. Methods Related mechanisms were investigated by DRG single‐cell sequencing analysis and use specific inhibitors in cellular experiments. In animal experiments, 32 male Sprague–Dawley rats randomly divided into sham operation group, CCI ibuprofen group. We performed behavioral tests, ELISA, H&E staining immunohistochemistry, western blotting. Results Cell communication reveals that after peripheral nerve injury, Schwann cells secrete IL‐34 act on CSF1R macrophages. After mRNA expression levels pathway NLRP3 inflammasome macrophages increased DRG. vitro studies demonstrated can reduce secretion LPS‐induced RSC96 cells; treatment cell‐conditioned medium (L‐S‐CM) does not induce proliferation migration RAW264.7 macrophages; L‐S‐CM reduces signaling (CSF1R, P38MAPK, NFκB) activation, ROS production. vivo experiments have verified thermal cold hyperalgesia rat chronic compressive injury (CCI) model; IL‐1β, IL‐6, TNF‐α, CCL2, SP, PGE2 serum rats; immunohistochemistry blot confirmed IL‐34/CSF1R rats. Conclusion Stigmasterol alleviates pain reducing cell‐macrophage cascade modulating axis.

Language: Английский

Citations

9
Bidirectional two-sample Mendelian randomization analysis reveals a causal effect of interleukin-18 levels on postherpetic neuralgia risk DOI Creative Commons
Liang Xiao, Yuchao Fan

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 25, 2023

Postherpetic neuralgia (PHN) is a debilitating complication of herpes zoster, characterized by persistent neuropathic pain that significantly impairs patients' quality life. Identifying factors determine PHN susceptibility crucial for its management. Interleukin-18 (IL-18), pro-inflammatory cytokine implicated in chronic pain, may play critical role development.In this study, we conducted bidirectional two-sample Mendelian randomization (MR) analyses to assess genetic relationships and potential causal associations between IL-18 protein levels increasing risk, utilizing genome-wide association study (GWAS) datasets on these traits. Two obtained from the EMBL's European Bioinformatics Institute database which contained 21,758 individuals with 13,102,515 SNPs Complete GWAS summary data 3,394 5,270,646 SNPs. The dataset FinnGen biobank had 195,191 16,380,406 SNPs.Our findings two different suggest correlation genetically predicted elevations an increased PHN.(IVW, OR 95% CI: 2.26, 1.07 4.78; p = 0.03 2.15, 1.10 4.19; =0.03, respectively), potentially indicating effect risk. However, did not detect any liability risk levels.These new insights into identifying at developing aid development novel prevention treatment approaches PHN.

Language: Английский

Citations

17
Curcumin relieves oxaliplatin‐induced neuropathic pain via reducing inflammation and activating antioxidant response DOI

Mengwei Zhang,

Xu Sun, Yiwen Xu

et al.

Cell Biology International, Journal Year: 2024, Volume and Issue: 48(6), P. 872 - 882

Published: March 13, 2024

Abstract Oxaliplatin (OXA) has shown high effectiveness in the treatment of cancers, but its anticancer clinical effects often induce neurotoxicity leading to neuropathic pain. Oxidative damage and NLRP3 inflammasome play important roles pain development. Here, mouse model was constructed by continuous intraperitoneal injection OXA. OXA administration induced mechanical pain, spontaneous thermal hyperalgesia motor disability mice. The spinal cord tissues mice exhibited suppressed antioxidative response, activated mediated inflammatory responses, increased GSK‐3β activity. Next, we injected curcumin (CUR) intraperitoneally for seven consecutive days. CUR‐treated showed thresholds, reduced number flinches, paw withdrawal latency, restored latency fall. While cord, CUR inhibited Nrf2/GPX4‐mediated antioxidant decreased mitochondrial oxidative generation. Additionally, combined with through four covalent bonds In conclusion, our findings suggest that inhibits activation, increases Nrf2 reaction, alleviates OXA‐induced

Language: Английский

Citations

6
Astrocyte modulation in cerebral ischemia-reperfusion injury: A promising therapeutic strategy DOI
Ziyu Wang, Xiaolu Zhang, Guangming Zhang

et al.

Experimental Neurology, Journal Year: 2024, Volume and Issue: 378, P. 114814 - 114814

Published: May 16, 2024

Language: Английский

Citations

5
Pyroptosis in Diabetic Peripheral Neuropathy and its Therapeutic Regulation DOI Creative Commons
Abdullah Al Mamun, Chuxiao Shao, Peiwu Geng

et al.

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 3839 - 3864

Published: June 1, 2024

Pyroptosis is a pro-inflammatory form of cell death resulting from the activation gasdermins (GSDMs) pore-forming proteins and release several factors. However, inflammasomes are intracellular protein complexes that cleave gasdermin D (GSDMD), leading to formation robust membrane pores initiation pyroptosis. Inflammasome gasdermin-mediated pore important intrinsic processes in classical pyroptotic signaling pathway. Overactivation NOD-like receptor thermal domain associated 3 (NLRP3) inflammasome triggers pyroptosis amplifies inflammation. Current evidence suggests overactivation may further induce progression cancers, nerve injury, inflammatory disorders metabolic dysfunctions. also indicates pyroptosis-dependent accelerates diabetes its frequent consequences including diabetic peripheral neuropathy (DPN). Pyroptosis-mediated reaction exacerbates DPN-mediated CNS injury. Accumulating shows molecular mechanisms trigger insulin-producing cells, development DPN. Numerous studies have suggested certain natural compounds or drugs possess promising pharmacological properties by modulating pyroptosis, thereby offering potential preventive practical therapeutic approaches for treatment management This review elaborates on underlying explores possible strategies regulating pyroptosis-regulated

Language: Английский

Citations

4