Environmental Enrichment for Stroke and Traumatic Brain Injury: Mechanisms and Translational Implications DOI

Luwei Nie,

Jinxin He,

Junmin Wang

et al.

Comprehensive physiology, Journal Year: 2023, Volume and Issue: unknown, P. 5291 - 5323

Published: Dec. 29, 2023

Abstract Acquired brain injuries, such as ischemic stroke, intracerebral hemorrhage (ICH), and traumatic injury (TBI), can cause severe neurologic damage even death. Unfortunately, currently, there are no effective safe treatments to reduce the high disability mortality rates associated with these injuries. However, environmental enrichment (EE) is an emerging approach treating rehabilitating acquired injuries by promoting motor, sensory, social stimulation. Multiple preclinical studies have shown that EE benefits functional recovery, including improved motor cognitive function psychological mediated complex protective signaling pathways. This article provides overview of enriched environment protocols used in animal models ICH, TBI, well relevant clinical studies, a particular focus on stroke. Additionally, we explored animals stroke TBI exposed alone or combination multiple drugs other rehabilitation modalities. Finally, discuss potential applications future therapy molecular cellular changes caused rodents TBI. aims advance research for injury. © 2024 American Physiological Society. Compr Physiol 14:5291‐5323, 2024.

Language: Английский

Oxytocin Improves Intracerebral Hemorrhage Outcomes by Suppressing Neuronal Pyroptosis and Mitochondrial Fission DOI Open Access
Miaoxian Yang, Shuixiang Deng, Junliang Jiang

et al.

Stroke, Journal Year: 2023, Volume and Issue: 54(7), P. 1888 - 1900

Published: June 15, 2023

BACKGROUND: Intracerebral hemorrhage (ICH) causes severe sensorimotor dysfunction and cognitive decline which are aggravated by secondary brain injury, yet there no effective management to alleviate these outcomes. Pyroptosis is strongly related neuroinflammation, plays a crucial role in the pathophysiological processes of injury after ICH. OXT (oxytocin), as pleiotropic neuropeptide, has multiple functions including anti-inflammation antioxidation. This study aims investigate improving ICH outcomes underlying mechanisms. METHODS: C57BL/6 mice were used establish model autologous blood injection. was administered intranasally (0.2 μg/g) Combing behavioral tests, Western blot, immunofluorescence staining, electron microscopy, pharmacological approaches, we evaluated effect intranasal application on neurological explored mechanism. RESULTS: Endogenous level decreased, whereas OXTR (oxytocin receptor) expression increased treatment improved short-term long-term alleviated neuronal pyroptosis neuroinflammation. In addition, reduced excessive mitochondrial fission mitochondrial-derived oxidative stress 3 days decreased pyroptotic proinflammatory factors NLRP3 (NOD-like receptor protein 3), ASC (apoptosis-associated speck-like containing CARD), GSDMD (gasdermin D), caspase-1, IL (interleukin)-1β, IL-18 p-PKA (phospho-protein kinase A) p-DRP1 (S637; DRP1 [dynamin-related 1] phosphorylation at Ser637). OXT-induced neuroprotective effects blocked either inhibitor or PKA inhibitor. CONCLUSIONS: Intranasal can ameliorate deficits neural pyroptosis, inflammation, via OXTR/p-PKA/DRP1 signaling pathway Thus, administration may be potential therapeutic strategy improve prognosis

Language: Английский

Citations

32
Inflammation in intracerebral hemorrhage: A bibliometric perspective DOI Creative Commons
Rui Zhang,

Ruoqi Ding,

Qiao Wang

et al.

Brain Hemorrhages, Journal Year: 2024, Volume and Issue: 5(3), P. 107 - 116

Published: Jan. 20, 2024

Intracerebral hemorrhage (ICH) is a severe stroke that can adversely affect patient outcomes due to the accompanying inflammatory response. As result, there growing interest in studying inflammation ICH. We systematically reviewed relevant articles using Web of Science understand literature on this subject. This study aims provide comprehensive overview field through bibliometric analysis, highlight its current status, identify frontiers, and speculate future directions. conducted analysis global English related ICH research based from 1993 present address publication trends hotspots. A total 885 publications were included 2023. These authored by 7,375 researchers 1,639 organizations 68 countries published 571 journals. Collectively, they cited 48,980 references 5,621 The author who most was Dr. Zhang, John H. Interestingly, 6 top ten authors China. Regarding articles, China at list, followed United States. frequently used keywords "Inflammation", "Neuroinflammation", "Microglia". journal reference citations, Stroke journal. Over past 30 years, has been considerable progress scientific concerning context pivotal themes these studies have immune cells mediators. It worth noting, however, pertains preclinical studies, with comparatively fewer clinical investigations. Several challenges must be addressed translate promising achievements into practice.

Language: Английский

Citations

8
LDC7559 inhibits microglial activation and GSDMD-dependent pyroptosis after subarachnoid hemorrhage DOI Creative Commons

Cai Wen-hua,

Zhe Wu, Jinqing Lai

et al.

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

Published: March 29, 2023

Mounting evidence indicates that inhibition of microglial activation and neuronal pyroptosis plays important roles in brain function recovery after subarachnoid hemorrhage (SAH). LDC7559 is a newly discovered gasdermin D (GSDMD) inhibitor. Previous studies have demonstrated could inhibit proliferation pyroptosis. However, the beneficial effects on SAH remain obscure. Based this background, we investigated potential role mechanism SAH-induced damage both vivo vitro . The findings revealed were evidently increased SAH, which be markedly suppressed by vitro. Meanwhile, treatment reduced apoptosis improved behavior function. Mechanistically, decreased levels GSDMD cleaved SAH. In contrast, nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome nigericin GSDMD-mediated abated damage. did not significantly affect expression NLRP3 Taken together, might suppress inhibiting GSDMD, thereby promoting functional recovery.

Language: Английский

Citations

16
CD22 blockade modulates microglia activity to suppress neuroinflammation following intracerebral hemorrhage DOI Creative Commons
Honglei Ren,

Pan Yan,

Danni Wang

et al.

Pharmacological Research, Journal Year: 2023, Volume and Issue: 196, P. 106912 - 106912

Published: Sept. 9, 2023

Microglia are first responders to acute brain insults and initiate neuroinflammation drive secondary tissue injury. Yet the key molecular switches in control of inflammatory activity microglia remain poorly understood. Intracerebral hemorrhage (ICH) is a devastating stroke subtype whereby hematoma formed within parenchyma associated with high mortality. Using mouse model ICH, we found upregulation CD22 that predominantly occurred microglia. Antibody blockade led reduction neurological deficits, lesion volume. This was accompanied by reduced activity, increased expression alternative activation markers (CD206 IL-10) enhanced phagocytosis after ICH. also an increase phosphorylated SYK AKT Notably, benefits were ablated ICH mice subjected microglial depletion colony-stimulating factor 1 receptor inhibitor PLX5622. Additionally, protective effects diminished receiving R406. Together, our findings highlight as switch detrimental injury, provide novel strategy improve outcome

Language: Английский

Citations

16
Treatment of Intracerebral Hemorrhage with Traditional Chinese Medicine Monomer Wogonin by Modifying NLRP3 with METTL14 to Inhibit Neuronal Cell Pyroptosis DOI
Libo Li,

Jinbing Gong,

Wenjia Zhang

et al.

Applied Biochemistry and Biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 15, 2024

Language: Английский

Citations

5
Cholesterol metabolism: physiological versus pathological aspects in intracerebral hemorrhage DOI Creative Commons
Ruoyu Huang,

Qiuyu Pang,

Lexin Zheng

et al.

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(4), P. 1015 - 1030

Published: April 3, 2024

Cholesterol is an important component of plasma membranes and participates in many basic life functions, such as the maintenance cell membrane stability, synthesis steroid hormones, myelination. plays a key role establishment central nervous system. The brain contains 20% whole body’s cholesterol, 80% which located within myelin. A huge number processes (e.g., sterol regulatory element-binding protein pathway liver X receptor pathway) participate regulation cholesterol metabolism via mechanisms that include biosynthesis, intracellular transport, efflux. Certain injuries or diseases involving crosstalk among above can affect normal to induce detrimental consequences. Therefore, we hypothesized cholesterol-related molecules pathways serve therapeutic targets for system diseases. Intracerebral hemorrhage most severe hemorrhagic stroke subtype, with high mortality morbidity. Historical levels are associated risk intracerebral hemorrhage. Moreover, secondary pathological changes after dysregulation, neuroinflammation, demyelination, multiple types programmed death. Intracellular accumulation has been found In this paper, review system, known disturbance hemorrhage, links between We also several possible constructive identified based on provide cholesterol-based perspectives reference those interested treatment

Language: Английский

Citations

5
P2Y6 Receptor Activation Aggravates NLRP3-dependent Microglial Pyroptosis via Downregulation of the PI3K/AKT Pathway in a Mouse Model of Intracerebral Hemorrhage DOI
Yulong Li,

Huiru Tu,

Shengfan Zhang

et al.

Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 61(7), P. 4259 - 4277

Published: Dec. 11, 2023

Language: Английский

Citations

13
Knockdown of LCN2 Attenuates Brain Injury After Intracerebral Hemorrhage via Suppressing Pyroptosis DOI Creative Commons
Yangyang Zhao, Qiuxiang Xiao, Tao Sun

et al.

Neuropsychiatric Disease and Treatment, Journal Year: 2024, Volume and Issue: Volume 20, P. 83 - 99

Published: Jan. 1, 2024

Objective: The aims of this study are to screen novel differentially expressed genes (DEGs) for intracerebral hemorrhage (ICH) and reveal the role Lipocalin-2 (LCN2) in ICH. Methods: We constructed ICH model by injection autologous whole blood into right basal ganglia rats. RNA-sequencing bioinformatics analyses were performed identify DEGs between sham rats, some important ones confirmed using quantitative real-time PCR (qRT-PCR). LCN shRNA was used knockdown LCN2 Pathological examination carried out 2,3,5-triphenyltetrazolium chloride (TTC) staining Hematoxylin-eosin (HE) staining. Immunohistochemistry detected Caspase-3, co-staining Terminal dUTP nick end labeling (TUNEL) NEUN neuron apoptosis assessment. Western blot analysis quantify pyroptosis-related proteins. Enzyme-linked immunosorbent assay (ELISA) measure inflammatory cytokine levels. Results: rats exhibited significant hematomas, higher brain water content, obvious interstitial edema, infiltration, as well more apoptotic cells tissues. RNA-seq identified 103 upregulated 81 downregulated DEGs. expression LCN2, HSPB1, CXCL10, MEF2B triggered release interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), IL-18, promoted proteins Caspase-1, GSDMD, NLRP3, ASC. attenuated pathological characteristics ICH, also reduced pyroptosis Conclusion: Inhibition attenuates injury after via suppressing pyroptosis, which provide guidance management. Keywords: hemorrhage, inflammation, lipocalin-2

Language: Английский

Citations

4
Exosomal MicroRNA: an Effective Strategy for the Treatment of Intracerebral Hemorrhage DOI
Yue Sun, Jiawei Liu,

Wentao Sun

et al.

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Language: Английский

Citations

0
Ruxolitinib Ameliorates Neuronal Pyroptosis in the Acute Phase of Intracerebral Hemorrhage through Inhibiting the Activation of Caspase-8 DOI
Guang Chen, Miao‐Kun Sun, Mingming Li

et al.

ACS Chemical Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: April 26, 2025

Intracerebral hemorrhage (ICH) is a common type of stroke with higher rates death and neurological dysfunction than ischemic stroke. Based on previous studies, we found that reducing neuronal pyroptosis in the acute phase ICH improved mice suffered from nontraumatic parenchymal hemorrhage. Still, mechanism must be further explored. In this study, used ruxolitinib, selective inhibitor JAK1/2, to treat CD-1 ICH. We inhibition JAK1/STAT1 pathway alleviated ICH-induced activation caspase-8 was suppressed at same time. Given crosstalk for different types programmed cell its role pyroptotic after has not yet been defined, administered z-IETD-fmk, caspase-8, downregulation reversed motor cognitive functions Our results show JAK1/STAT1/caspase-8 axis critical mediator Inhibiting outcomes ICH, propose ruxolitinib as potential therapeutic approach post-ICH treatment.

Language: Английский

Citations

0