Insulin-Like Growth Factor-1 Is Neuroprotective in Aged Rats With Ischemic Stroke DOI Creative Commons
Ahmad Serhan, Erik Boddeke, Ron Kooijman

et al.

Frontiers in Aging Neuroscience, Journal Year: 2019, Volume and Issue: 11

Published: Dec. 11, 2019

Post-stroke systemic injections of insulin-like growth factor 1 (IGF-1) exert neuroprotective effects in rats. In the current study, we aimed to test efficacy IGF-1 neuroprotection aged rats (24-25 months old) and compare results with adult (6-7 old). Furthermore, addressed putative differences microglial responses Rats were subjected ischemic stroke while they conscious by infusing endothelin-1 (Et-1) through a guide cannula that was implemented vicinity middle cerebral artery (MCA). given subcutaneous (1 mg/kg) at 30 min 120 after insult. treatment reduced infarct size 34% 38% rats, respectively. The treated also showed significant improvement sensorimotor function following stroke, this not significantly affected displayed exaggerated activation microglia hemisphere. Significant reduction only detected specific regions ipsilateral hemisphere We show an stroke. It remains be established, however, whether age-related changes affect behavioral outcome.

Language: Английский

Novel targets, treatments, and advanced models for intracerebral haemorrhage DOI Creative Commons
Marietta Zille, Tracy D. Farr, Richard F. Keep

et al.

EBioMedicine, Journal Year: 2022, Volume and Issue: 76, P. 103880 - 103880

Published: Feb. 1, 2022

Language: Английский

Citations

94
Microglial vesicles improve post-stroke recovery by preventing immune cell senescence and favoring oligodendrogenesis DOI Creative Commons
Stefano Raffaele, Paolo Gelosa, Elisabetta Bonfanti

et al.

Molecular Therapy, Journal Year: 2020, Volume and Issue: 29(4), P. 1439 - 1458

Published: Dec. 10, 2020

Contrasting myelin damage through the generation of new myelinating oligodendrocytes represents a promising approach to promote functional recovery after stroke. Here, we asked whether activation microglia and monocyte-derived macrophages affects regenerative process sustained by G protein-coupled receptor 17 (GPR17)-expressing oligodendrocyte precursor cells (OPCs), subpopulation OPCs specifically reacting ischemic injury. GPR17-iCreERT2:CAG-eGFP reporter mice were employed trace fate GPR17-expressing OPCs, labeled green fluorescent protein (GFP), permanent middle cerebral artery occlusion. By microglia/macrophages pharmacological depletion studies, show that innate immune favor GFP+ OPC reaction limit early injury, whereas they lose their pro-resolving capacity acquire dystrophic "senescent-like" phenotype at later stages. Intracerebral infusion microglia-derived extracellular vesicles (EVs) restores protective functions, limiting senescence during post-stroke phase, enhances maturation lesion borders, resulting in ameliorated neurological functionality. In vitro experiments EV-carried transmembrane tumor necrosis factor (tmTNF) mediates pro-differentiating effects on with future implications for therapies.

Language: Английский

Citations

80
Stem Cells as an Emerging Paradigm in Stroke 4 DOI Open Access
Johannes Boltze, Michel Modo, Robert Mays

et al.

Stroke, Journal Year: 2019, Volume and Issue: 50(11), P. 3299 - 3306

Published: Oct. 17, 2019

Language: Английский

Citations

76
Injectable hydrogel enables local and sustained co-delivery to the brain: Two clinically approved biomolecules, cyclosporine and erythropoietin, accelerate functional recovery in rat model of stroke DOI
Anup Tuladhar, Jaclyn M. Obermeyer, Samantha L. Payne

et al.

Biomaterials, Journal Year: 2020, Volume and Issue: 235, P. 119794 - 119794

Published: Jan. 16, 2020

Language: Английский

Citations

60
From the Lab to Patients: a Systematic Review and Meta-Analysis of Mesenchymal Stem Cell Therapy for Stroke DOI
Manoj M. Lalu, Joshua Montroy, Dar Dowlatshahi

et al.

Translational Stroke Research, Journal Year: 2019, Volume and Issue: 11(3), P. 345 - 364

Published: Oct. 25, 2019

Language: Английский

Citations

58
Edaravone Ameliorates Cerebral Ischemia–Reperfusion Injury by Downregulating Ferroptosis <i>via</i> the Nrf2/FPN Pathway in Rats DOI Open Access
Wenpeng Liu, Linlin Wang,

Canwen Liu

et al.

Biological and Pharmaceutical Bulletin, Journal Year: 2022, Volume and Issue: 45(9), P. 1269 - 1275

Published: Aug. 31, 2022

Edaravone, an antioxidant protective agent, has anti-cerebral ischemic reperfusion injury (CIRI) effects, but its anti-CIRI mechanism is unclear. The aim of this study to investigate the edaravone based on nuclear factor-E2-related factor 2 (Nrf2)/ferroportin (FPN) pathway that regulates ferroptosis-mediated cerebral ischemia-reperfusion injury. We evaluated brain by constructing a middle artery occlusion and (MCAO/R) model in rats. results showed infarct volume neurological impairment scores were increased rats, with impaired sensorimotor ability; furthermore, tissue glutathione (GSH) content was decreased, Fe2+, malondialdehyde (MDA) lipide peroxide (LPO) increased, expression level peroxidase 4 (GPX4), key protein ferroptosis, also decreased. Meanwhile, Nrf2 FPN decreased after ischemia-reperfusion, while levels interleukin (IL)-6, IL-1β, tumor necrosis (TNF)-α, myeloperoxidase (MPO) increased. However, exhibited effect function relevant tests. In addition, we found contents MDA, LPO MCAO/R rats GSH inhibit ferroptosis. Furthermore, Western blot treatment edaravone, Nrf2, GPX4, up-regulated, location inflammation-related indicators IL-6, TNF-α, MPO lower than group. Our demonstrated inhibits ferroptosis attenuate CIRI, probably through activation Nrf2/FPN pathway.

Language: Английский

Citations

33
Measuring the Frequency-Specific Functional Connectivity Using Wavelet Coherence Analysis in Stroke Rats Based on Intrinsic Signals DOI Creative Commons

Leila Mohammadzadeh,

Hamid Latifi, Sepideh Khaksar

et al.

Scientific Reports, Journal Year: 2020, Volume and Issue: 10(1)

Published: June 10, 2020

Abstract Optical intrinsic signal imaging (OISi) method is an optical technique to evaluate the functional connectivity (FC) of cortex in animals. Already, using OISi, FC has been measured time or frequency domain separately, and at frequencies below 0.08 Hz, which not range hemodynamic oscillations are able track fast cortical events, including neurogenic, myogenic, cardiac respiratory activities. In current work, we calculated wavelet coherence (WC) transform OISi series cerebral response changes stroke rats. Utilizing WC, up 4.5 could monitor dependency simultaneously. The results showed that WC brain diminished significantly ischemic motor somatosensory cortices. According statistical results, amplitude, responsive area size, correlation, cortices for hemisphere were found be lower compared healthy hemisphere. obtained confirm OISi-based analysis efficient diagnose relative severity infarction size infarcted region after stroke.

Language: Английский

Citations

43
Lithium modulates miR-1906 levels of mesenchymal stem cell-derived extracellular vesicles contributing to poststroke neuroprotection by toll-like receptor 4 regulation DOI Creative Commons
Matteo Haupt, Xuan Zheng, Yaoyun Kuang

et al.

Stem Cells Translational Medicine, Journal Year: 2020, Volume and Issue: 10(3), P. 357 - 373

Published: Nov. 4, 2020

Lithium is neuroprotective in preclinical stroke models. In addition to that, poststroke neuroregeneration stimulated upon transplantation of mesenchymal stem cells (MSCs). Preconditioning MSCs with lithium further enhances the neuroregenerative potential MSCs, which act by secreting extracellular vesicles (EVs). The present work analyzed whether MSC preconditioning modifies EV secretion patterns, enhancing therapeutic such derived EVs (Li-EVs) comparison enriched from native MSCs. Indeed, Li-EVs significantly enhanced resistance cultured astrocytes, microglia, and neurons against hypoxic injury when compared controls EV-treated cells. Using a mouse model, intravenous delivery increased neurological recovery for as long 3 months mice, albeit latter also showed better behavioral test performance controls. changed patterns EVs, modifying contents various miRNAs within these vesicles. As such, displayed levels miR-1906, has been shown be new regulator toll-like receptor 4 (TLR4) signaling. reduced posthypoxic postischemic TLR4 abundance, resulting an inhibition nuclear factor kappa-light-chain-enhancer activated B (NF-κB) signaling pathway, decreased proteasomal activity, declined both inducible NO synthase cyclooxygenase-2 expression, all culminated cerebral inflammation. Conclusively, study demonstrates, first time, interfering novel pathway that yields acute neuroprotection recovery.

Language: Английский

Citations

43
The Effect of Exosomes Derived from Bone Marrow Stem Cells in Combination with Rosuvastatin on Functional Recovery and Neuroprotection in Rats After Ischemic Stroke DOI

Mohsen Safakheil,

Hosein Safakheil

Journal of Molecular Neuroscience, Journal Year: 2020, Volume and Issue: 70(5), P. 724 - 737

Published: Jan. 23, 2020

Language: Английский

Citations

41
Growth Hormone Improves Cognitive Function After Experimental Stroke DOI Open Access
Lin Kooi Ong,

Wei Zhen Chow,

Clifford TeBay

et al.

Stroke, Journal Year: 2018, Volume and Issue: 49(5), P. 1257 - 1266

Published: April 10, 2018

Cognitive impairment is a common outcome for stroke survivors. Growth hormone (GH) could represent potential therapeutic option as this peptide has been shown to improve cognition in various clinical conditions. In study, we evaluated the effects of peripheral administration GH at 48 hours poststroke 28 days on cognitive function and underlying mechanisms.Experimental was induced by photothrombotic occlusion young adult mice. We assessed associative memory domain using mouse touchscreen platform paired-associate learning task. also neural tissue loss, neurotrophic factors, markers neuroplasticity cerebrovascular remodeling biochemical histology analyses.Our results show that GH-treated stroked mice made significant improvement task relative non-GH-treated end study. Furthermore, observed reduction loss identified treatment resulted significantly higher levels factors (IGF-1 [insulin-like growth factor-1] VEGF [vascular endothelial factor]) both circulatory peri-infarct regions. not only promoted protein density presynaptic marker (SYN-1 [synapsin-1]) myelination (MBP [myelin basic protein]) but increased area coverage 2 major vasculature (CD31 collagen-IV), within region.These findings provide compelling preclinical evidence usage tool recovery phase patients after stroke.

Language: Английский

Citations

46