Inhibition of S100A8/A9 ameliorates neuroinflammation by blocking NET formation following traumatic brain injury DOI Creative Commons

Guihong Shi,

Yiyao Cao,

Jianye Xu

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: 81, P. 103532 - 103532

Published: Feb. 5, 2025

Traumatic brain injury (TBI) triggers a robust inflammatory response that is closely linked to worsened clinical outcomes. S100A8/A9, also known as calprotectin or myeloid-related protein-8/14 (MRP8/14), an alarmin primarily secreted by activated neutrophils with potent pro-inflammatory property. In this study, we explored the roles of S100A8/A9 in modulating neuroinflammation and influencing TBI outcomes, delving into underlying mechanisms. S100A8/A9-enriched were present injured tissue patients, elevated plasma levels correlated poorer neurological function. Furthermore, using mouse model, demonstrated treatment selective inhibitor Paquinimod significantly mitigated neuronal death, thereby improving prognosis mice. Mechanistically, found conjunction neutrophil activation infiltration brain, enhances reactive oxygen species (ROS) production within neutrophils, accelerating PAD4-mediated extracellular trap (NET) formation, which turn exacerbates neuroinflammation. These findings suggest amplifies neuroinflammatory responses promoting NET formation neutrophils. Inhibition effectively attenuated NET-mediated neuroinflammation; however, when PAD4 was overexpressed adenovirus, leading increased anti-inflammatory effects inhibition markedly diminished. Further experiments knockout mice confirmed reduction NETs could substantially alleviate S100A8/A9-driven Finally, established suppression mediated through AMPK/Nrf2/HO-1 signaling pathway. underscore critical pathological role emphasize need for further exploration potential therapeutic strategy TBI.

Language: Английский

Context is key: glucocorticoid receptor and corticosteroid therapeutics in outcomes after traumatic brain injury DOI Creative Commons

Morgan Taylor,

Olga N. Kokiko‐Cochran

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: March 11, 2024

Traumatic brain injury (TBI) is a global health burden, and survivors suffer functional psychiatric consequences that can persist long after injury. TBI induces physiological stress response by activating the hypothalamic-pituitary-adrenal (HPA) axis, but effects of on become more complex in term. Clinical experimental evidence suggests lasting dysfunction TBI. Additionally, pre- post-injury both have negative impacts outcome following This bidirectional relationship between impedes recovery exacerbates TBI-induced cognitive dysfunction. Previous clinical studies explored use synthetic glucocorticoids as therapeutic for stress-related outcomes, these yielded mixed results. Furthermore, long-term steroid treatment associated with multiple side effects. There pressing need alternative approaches improve functionality Glucocorticoid receptor (GR) has been identified fundamental link immune responses, preclinical GR plays an important role microglia-mediated outcomes other neuroinflammatory conditions. In this review, we will summarize GR-mediated TBI, highlighting microglia. We discuss recent which target microglial context injury, suggest cell-specific interventions may be promising strategy pathophysiology.

Language: Английский

Citations

4
Molecular insights into Parkinson's disease and type 2 diabetes mellitus: Metformin's role and genetic pathways explored DOI

Tingting Liu,

Haojie Wu,

Jianshe Wei

et al.

Experimental Neurology, Journal Year: 2025, Volume and Issue: 385, P. 115137 - 115137

Published: Jan. 10, 2025

Language: Английский

Citations

0
Puerarin Mitigates Cognitive Decline and White Matter Injury via CD36-Mediated Microglial Phagocytosis in Chronic Cerebral Hypoperfusion DOI
Qinghua Luo, Fang Li, Xu Liu

et al.

Phytomedicine, Journal Year: 2025, Volume and Issue: 138, P. 156396 - 156396

Published: Jan. 16, 2025

Language: Английский

Citations

0
Serendipity Can Rule the Day: Remarkable Efficacy of a Mushroom Extract Powder in Childhood Treatment Resistant Epilepsy DOI

Olivia Kim-McManus,

Sarah Boylan,

Mark Nespeca

et al.

Pediatric Neurology, Journal Year: 2025, Volume and Issue: 165, P. 56 - 59

Published: Jan. 25, 2025

Language: Английский

Citations

0
Inhibition of S100A8/A9 ameliorates neuroinflammation by blocking NET formation following traumatic brain injury DOI Creative Commons

Guihong Shi,

Yiyao Cao,

Jianye Xu

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: 81, P. 103532 - 103532

Published: Feb. 5, 2025

Traumatic brain injury (TBI) triggers a robust inflammatory response that is closely linked to worsened clinical outcomes. S100A8/A9, also known as calprotectin or myeloid-related protein-8/14 (MRP8/14), an alarmin primarily secreted by activated neutrophils with potent pro-inflammatory property. In this study, we explored the roles of S100A8/A9 in modulating neuroinflammation and influencing TBI outcomes, delving into underlying mechanisms. S100A8/A9-enriched were present injured tissue patients, elevated plasma levels correlated poorer neurological function. Furthermore, using mouse model, demonstrated treatment selective inhibitor Paquinimod significantly mitigated neuronal death, thereby improving prognosis mice. Mechanistically, found conjunction neutrophil activation infiltration brain, enhances reactive oxygen species (ROS) production within neutrophils, accelerating PAD4-mediated extracellular trap (NET) formation, which turn exacerbates neuroinflammation. These findings suggest amplifies neuroinflammatory responses promoting NET formation neutrophils. Inhibition effectively attenuated NET-mediated neuroinflammation; however, when PAD4 was overexpressed adenovirus, leading increased anti-inflammatory effects inhibition markedly diminished. Further experiments knockout mice confirmed reduction NETs could substantially alleviate S100A8/A9-driven Finally, established suppression mediated through AMPK/Nrf2/HO-1 signaling pathway. underscore critical pathological role emphasize need for further exploration potential therapeutic strategy TBI.

Language: Английский

Citations

0