Targeted Pyroptosis with Resveratrol Nanoparticles to Reduce Secondary Brain Injury and Post-Traumatic Epilepsy DOI

Zhengzhong Han,

Zeqi Zhao,

Lansheng Wang

et al.

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 20, 2024

Traumatic brain injury (TBI) is associated with high mortality and disability rates globally, leading to significant sequelae, particularly post-traumatic epilepsy (PTE), which severely impacts physical health quality of life. TBI involves primary secondary damage, the latter exacerbating initial through neuroinflammation, influencing overall outcome. Recent studies highlight pyroptosis as a crucial factor in spread damage development epilepsy, making it vital therapeutic target. While current treatments focus on surgical medical interventions reduce intracranial pressure, addressing has limited clinical translation, largely due blood-brain barrier (BBB) hindering drug accumulation affected area. Resveratrol (RV) shows promise agent its anti-inflammatory properties. This study presents nanoliposome (C-Lips/RV) engineered cysteine-alanine-glutamine-lysine peptides enhance RV delivery brain, mitigate pyroptosis, inflammation. In rats, C-Lips/RV demonstrates longer half-life effective targeting injury, reduced PTE, slowed progression, improved functional recovery. work offers insights into managing PTE.

Language: Английский

TREM2 affects DAM-like cell transformation in the acute phase of TBI in mice by regulating microglial glycolysis DOI Creative Commons

Lin Wang,

Dengjie Ouyang,

Li Lin

et al.

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: Jan. 13, 2025

Traumatic brain injury (TBI) is characterized by high mortality and disability rates. Disease-associated microglia (DAM) are a newly discovered subtype of microglia. However, their presence function in the acute phase TBI remain unclear. Although glycolysis important for microglial differentiation, its regulatory role DAM transformation during still In this study, we investigated functions DAM-like cells mice, as well relationship between glycolysis. controlled cortical impact model was used to induce adult male wild-type (WT) C57BL/6 mice TREM2 knockout mice. Various techniques were assess effects on cells, including RT‒qPCR, immunofluorescence assays, behavioural tests, extracellular acidification rate (ECAR) Western blot analysis, cell magnetic sorting culture, glucose lactate flow cytometry. observed depended expression. impaired neurological recovery possibly due part clearing debris secreting VEGFa BDNF. Moreover, exhibited significantly increased glycolytic activity. regulated AKT‒mTOR‒HIF-1α pathway TBI. The increase partially contributed Taken together, results our study demonstrated that present might influence modulating Our provide new possible intervening

Language: Английский

Citations

3
Applications of hydrogels and nanoparticles in the treatment of traumatic brain injury DOI Creative Commons

Jiaying Shi,

Jiajia Tang, Xu Jin

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2025, Volume and Issue: 12

Published: Jan. 6, 2025

Traumatic brain injury (TBI) represents a significant global public health issue, with effective management posing numerous challenges. The pathophysiology of TBI is typically categorized into two phases: primary and secondary injuries. Secondary involves pathophysiological mechanisms such as blood-brain barrier (BBB) disruption, mitochondrial dysfunction, oxidative stress, inflammatory responses. Current pharmacological strategies often encounter obstacles in treating effectively, primarily due to challenges BBB penetration, inadequate target site accumulation, off-target toxicity. Versatile hydrogels nanoparticles offer potential solutions these limitations. This review discusses recent progress utilizing for treatment over the past 5 years, highlighting their relevance underlying pathophysiology. Hydrogels demonstrate substantial promise addressing injury, providing broad spectrum future therapeutic opportunities.

Language: Английский

Citations

2
Advanced Nanoparticle Engineering for Precision Therapeutics of Brain Diseases DOI
Muhammad Ismail, Jiayi Liu,

Ningyang Wang

et al.

Biomaterials, Journal Year: 2025, Volume and Issue: 318, P. 123138 - 123138

Published: Jan. 28, 2025

Language: Английский

Citations

1
Regulated cell death in hypoxic-ischaemic encephalopathy: recent development and mechanistic overview DOI Creative Commons
Lingzhi Wu, Enqiang Chang, Hailin Zhao

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: June 11, 2024

Abstract Hypoxic-ischaemic encephalopathy (HIE) in termed infants remains a significant cause of morbidity and mortality worldwide despite the introduction therapeutic hypothermia. Depending on cell type, cellular context, metabolic predisposition insult severity, death injured immature brain can be highly heterogenous. A continuum exists H/I-injured brain. Aside from apoptosis, emerging evidence supports pathological activation necroptosis, pyroptosis ferroptosis as alternative regulated (RCD) HIE to trigger neuroinflammation disturbances addition loss. Upregulation autophagy mitophagy represents an intrinsic neuroprotective strategy. Molecular crosstalk between RCD pathways implies one mechanism may compensate for loss function another. Moreover, mitochondrion was identified signalling “hub” where different converge. The highly-orchestrated nature makes them promising targets. Better understanding mechanisms subtypes likely shed light novel therapy development HIE. identification potential converging node open up opportunity simultaneous synergistic inhibition

Language: Английский

Citations

6
Single‐Cell RNA Sequencing Uncovers Molecular Features Underlying the Disrupted Neurogenesis Following Traumatic Brain Injury DOI Open Access
Cong Liu,

Fanghong Shao,

Xuan‐Cheng He

et al.

Glia, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide, with limited effective treatment strategies. Endogenous neural stem cells (NSCs) give rise to neurons glial throughout life. However, NSCs are more likely differentiate into rather than at the lesion site after TBI underlying molecular mechanism remains largely unknown. Here, we performed large-scale single-cell transcriptome sequencing subventricular zone (SVZ) NSCs-derived in mouse brain, provide evidence for previous observations that differentiation prevails TBI. In addition, show disrupted neurogenesis following caused by reduction NSC subcluster (NSC-4) expressing neuronal gene Tubb3. Finally, demonstrate transcriptional factor Dlx2 significantly downregulated NSC-4, overexpression sufficient drive towards lineage expense astrocytic under pro-inflammatory conditions.

Language: Английский

Citations

0
A review on brain-targeting nano-based drug delivery DOI
Peiying Li, Yaoxing Chen, Xiaoling Gao

et al.

Chinese Science Bulletin (Chinese Version), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Mitochondrial Transplantation via Magnetically Responsive Artificial Cells Promotes Intracerebral Hemorrhage Recovery by Supporting Microglia Immunological Homeostasis DOI Creative Commons

Mi Zhou,

J. Zang,

Yuxuan Qian

et al.

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

Published: Feb. 17, 2025

Abstract The immune‐inflammatory responses in the brain represent a key therapeutic target to ameliorate injury following intracerebral hemorrhage (ICH), where pro‐inflammatory microglia and its mitochondrial dysfunction plays pivotal role. Mitochondrial transplantation is promising strategy improve cellular function thus modulate their immune properties. However, of naked mitochondria into has been constrained by peripheral clearance difficulty achieving selective access brain. Here, novel for via intravenous injection magnetically responsive artificial cells (ACs) are proposed. ACs can protect loaded selectively accumulate around lesion under an external magnetic field (EMF). In this study, released from effectively microglial function, attenuate attributes, elevate proportion immunosuppressive microglia. way, homeostasis reestablished, inflammation attenuated, ultimately promoting functional recovery. This study presents effective approach transplant brain, offering alternative cascade ICH.

Language: Английский

Citations

0
Microglial pyroptosis induced by SENP7 via the cGAS/STING/IRF3 pathway contributes to neuronal apoptosis DOI

Lin Liu,

Fei Xiao, Jinyue Yang

et al.

Cytokine, Journal Year: 2025, Volume and Issue: 189, P. 156893 - 156893

Published: Feb. 24, 2025

Language: Английский

Citations

0
Responsive nanoparticles synergize with Curcumin to break the “reactive oxygen Species-Neuroinflammation” vicious cycle, enhancing traumatic brain injury outcomes DOI Creative Commons
Xianhua Fu, Yongkang Zhang, Guojie Chen

et al.

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 5, 2025

Traumatic brain injury (TBI) disrupts oxygen homeostasis in the brain, leading to excessive reactive species (ROS) production and dysregulated antioxidant mechanisms, which fail clear excess ROS. This ROS overload promotes expression of pro-inflammatory genes, releasing cytokines chemokines creating a vicious "ROS-neuroinflammation" cycle, making it essential break this cycle for effective TBI treatment. In study, we developed cysteine-alanine-glutamine-lysine (CAQK) peptide-modified nanoparticles (C-PPS/C) co-delivery curcumin (Cur) modulate oxidative neuroinflammatory disturbances after TBI. mice, C-PPS/C accumulated injured regions, where poly (propylene sulfide)120 scavenged ROS, reducing stress, while Cur release further suppressed inflammation. broke protecting blood-brain barrier (BBB), acute edema, promoting long-term neurological recovery. Further investigation showed that inhibited NF-κB pathway, gene mitigating inflammation, suggesting promising approach

Language: Английский

Citations

0
Cascade-Type Microglial Pyroptosis Inhibitors for Enhanced Treatment of Cerebral Ischemia-Reperfusion Injury DOI
Zhi-Fei Cheng, Wei Shao,

Chaoqi Wei

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

Neuroinflammation is a critical factor in the progression of cerebral ischemia-reperfusion injury (CIRI). Pyroptosis, which an inflammatory form programmed cell death, greatly amplifies neuroinflammatory processes. It does so by promoting release various contents that intensify overall response within central nervous system. Therefore, targeting pyroptosis represents promising therapeutic strategy for treatment CIRI. Excessive generation reactive oxygen species (ROS) overactivated microglia considered to serve as signal molecule triggers NLRP3 inflammasome-mediated pyroptosis. However, current inhibitors solely focus on eliminating existing ROS or inhibiting inflammasome are not optimal. Here, coating nanothylakoids (NTs) coengineered with fibrin-binding peptide and MG1 onto dihydrotanshinone I (DT)-loaded nanocarriers, we have developed cascade-type inhibitor (MDN-MC) comprehensively regulates ROS/NLRP3/pyroptosis axis. The incorporation catalase surface MDN-MC, along DT, facilitated cascade inhibition scavenging suppressing expression NLRP3. In rat model transient middle artery occlusion, enhanced behavioral recovery neuronal repair were achieved through at lesion site implementation interventions inhibit pyroptosis, thereby demonstrating effects. Overall, this work emphasizes importance cascade-regulated reducing neuroinflammation, offering important mechanistic understanding possible approaches

Language: Английский

Citations

0