Initial cell maturity changes following transplantation in a hyaluronan-based hydrogel and impacts therapeutic success in the stroke-injured rodent brain

Biomaterials, Journal Year: 2018, Volume and Issue: 192, P. 309 - 322

Published: Nov. 15, 2018

Language: Английский

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Systemic conditioned medium treatment from interleukin-1 primed mesenchymal stem cells promotes recovery after stroke

Stem Cell Research & Therapy, Journal Year: 2020, Volume and Issue: 11(1)

Published: Jan. 21, 2020

Mesenchymal stem cells (MSCs) hold great potential as a therapy for stroke and have previously been shown to promote recovery in preclinical models of cerebral ischaemia. MSCs secrete wide range growth factors, chemokines, cytokines extracellular vesicles-collectively termed the secretome. In this study, we assessed first time efficacy IL-1α-primed MSC-derived secretome on brain injury functional after ischaemia.Stroke was induced male C57BL/6 mice using intraluminal filament model middle artery occlusion. Conditioned medium from or vehicle administered at reperfusion 24 h post-stroke by subcutaneous injection.IL-1α-primed conditioned treatment led ~ 30% reduction lesion volume 48 associated with modest improvements body mass gain, 28-point neurological score nest building. Administration improved building despite no observed differences day 2 post-stroke.Our results show that administration leads behavioural outcomes independently neuroprotection.

Language: Английский

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More than motor impairment: A spatiotemporal analysis of cognitive impairment and associated neuropathological changes following cortical photothrombotic stroke

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2021, Volume and Issue: 41(9), P. 2439 - 2455

Published: March 28, 2021

There is emerging evidence suggesting that a cortical stroke can cause delayed and remote hippocampal dysregulation, leading to cognitive impairment. In this study, we aimed investigate motor outcomes after experimental stroke, their association with secondary neurodegenerative processes. Specifically, used photothrombotic model targeting the somatosensory cortices of mice. Motor function was assessed using cylinder grid walk tasks. Changes in cognition were mouse touchscreen platform. Neuronal loss, gliosis amyloid-β accumulation investigated peri-infarct ipsilateral regions at 7, 28 84 days post-stroke. Our findings showed persistent impairment post-stroke, whilst there modest spontaneous recovery over period days. region, detected reduction neuronal loss decreased neuroinflammation time which potentially explains recovery. Conversely, observed together concomitant increased hippocampus, likely accounts for dysfunction. indicate induces processes region from primary infarct, contributing progression post-stroke

Language: Английский

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Neuroinflammation in Ischemic Stroke: Inhibition of cAMP-Specific Phosphodiesterases (PDEs) to the Rescue

Biomedicines, Journal Year: 2021, Volume and Issue: 9(7), P. 703 - 703

Published: June 22, 2021

Ischemic stroke is caused by a thromboembolic occlusion of major cerebral artery, with the impaired blood flow triggering neuroinflammation and subsequent neuronal damage. Both innate immune system (e.g., neutrophils, monocytes/macrophages) in acute ischemic phase adaptive T cells, B cells) chronic contribute to this neuroinflammatory process. Considering that available therapeutic strategies are insufficiently successful, there an urgent need for novel treatment options. It has been shown increasing cAMP levels lowers neuroinflammation. By inhibiting cAMP-specific phosphodiesterases (PDEs), i.e., PDE4, 7, 8, can be tempered through elevating and, thereby, induce improved functional recovery. This review discusses recent preclinical findings, clinical implications, future perspectives PDE inhibition as research interest stroke. In particular, PDE4 extensively studied, promising following stroke, whereas PDE7 8 more target cell component. addition, targeted gene inhibition, or combined requires extensive research.

Language: Английский

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Reactive astrocytes prevent maladaptive plasticity after ischemic stroke

Progress in Neurobiology, Journal Year: 2021, Volume and Issue: 209, P. 102199 - 102199

Published: Dec. 16, 2021

Restoration of functional connectivity is a major contributor to recovery after stroke. We investigated the role reactive astrocytes in and photothrombotic stroke mice with attenuated gliosis (GFAP–/–Vim–/–). Infarct volume longitudinal changes were determined by vivo T2-weighted magnetic resonance imaging (MRI) resting-state MRI. Sensorimotor function was assessed behavioral tests, glial neural plasticity responses quantified peri-infarct region. Four weeks stroke, GFAP–/–Vim–/– showed impaired sensorimotor aberrant restoration global neuronal connectivity. These also exhibited maladaptive responses, shown higher number lost newly formed connections between primary secondary targets cortical regions increased expression axonal marker Gap43. conclude that modulate recovery-promoting ischemic

Language: Английский

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Behavioural assessment of neuropsychiatric outcomes in rodent stroke models

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

Stroke-associated mood disorders are less recognised than sensorimotor impairment, despite their high prevalence. Similarly, few experimental stroke studies assess non-sensorimotor functions. This study examined the prevalence and implementation of tests in three stroke-focused journals over last twenty years. Of 965 ischaemic papers which used behavioural testing rodents, 932 included testing, while 137 (most commonly Morris water maze, open field, Y-maze, novel object recognition tests, but with a more diverse range introduced recent years). Cognition, anxiety depression were assessed 70%, 27% 3% these papers. Non-sensorimotor deficits typically observed after recovery function. Potential confounding factors challenges for data interpretation identified most prevalent tests. More generally, rigor (a priori power calculation, randomisation, blinding, pre-defined inclusion/exclusion) improved years, remained unsatisfactory only 26% providing some evidence adequate statistical power. Furthermore, focused on male animals, limiting external validity. review confirms disparity between shows that share including latter is increasing. It essential research into neuropsychiatric sequalae addresses methodological issues noted continues to expand improve patient outcomes post-stroke.

Language: Английский

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Characterizing Spontaneous Motor Recovery Following Cortical and Subcortical Stroke in the Rat

Neurorehabilitation and neural repair, Journal Year: 2018, Volume and Issue: 33(1), P. 27 - 37

Published: Dec. 10, 2018

Background. Stroke is a leading cause of neurological disability, often resulting in long-term motor impairments due to damage cortical or subcortical areas. Despite the high prevalence strokes clinical population, preclinical research has primarily focused on investigating and treating strokes. Moreover, while both humans animals show spontaneous recovery following stroke, little known about how injury location affects this process. Objective. To capture heterogeneity human stroke examine cortical, subcortical, combination Methods. Endothelin-1 (ET-1), potent vasoconstrictor, was used produce focal infarcts forelimb cortex (FMC), dorsolateral striatum (DLS) FMC DLS male Sprague-Dawley rats. The profile followed over an 8-week period using battery behavioral tasks assessing function limb preference. Results. All 3 groups showed significant Montoya staircase, beam, cylinder tests with combined group (FMC + DLS) having largest most persistent impairments. Importantly, not simply dependent lesion volume, but location, test employed. Conclusions. markedly differentially influences level functional recovery, which only captured by multiple outcome measures. These results illustrate need for models align especially respect size,

Language: Английский

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Optimizing functional outcome endpoints for stroke recovery studies

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2019, Volume and Issue: 39(12), P. 2323 - 2342

Published: Sept. 14, 2019

Novel therapeutic intervention that aims to enhance the endogenous recovery potential of brain during subacute phase stroke has produced promising results. The paradigm shift in treatment approaches presents new challenges preclinical and clinical researchers alike, especially functional endpoints domain. Shortcomings “neuroprotection” era research are yet be fully addressed. Proportional observed clinics, potentially animal models, requires a thorough reevaluation methods used assess recovery. To this end, review give detailed evaluation outcome measures clinics studies. Impairments models will discussed from testing perspective. Approaches needed bridge gap between research, along with means measure moving target recovery, discussed. Concepts such as true function compensation suitable for distinguishing two examined. Often-neglected outcomes stroke, emotional disturbances, draw attention need further area.

Language: Английский

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Olfactory Mucosa Mesenchymal Stem Cells Alleviate Cerebral Ischemia/Reperfusion Injury Via Golgi Apparatus Secretory Pathway Ca2+ -ATPase Isoform1

Frontiers in Cell and Developmental Biology, Journal Year: 2020, Volume and Issue: 8

Published: Oct. 30, 2020

Olfactory mucosa mesenchymal stem cells (OM-MSCs) have exhibited their effectiveness in central nervous system diseases and provided an appealing candidate for the treatment of ischemic stroke. Previous evidence showed that Golgi apparatus (GA) secretory-pathway Ca2+-transport ATPases isoform1 (SPCA1) was a potential therapeutic target In this study, we explored neuroprotective mechanism OM-MSCs its effect on expression function SPCA1 during cerebral ischemia/reperfusion. Based vitro vivo experiments, discovered attenuated apoptosis oxidative stress stroke models, reduced infarction volume improved neurologic deficits rats. also upregulated alleviated Ca2+ overload, decreased edema dissolution GA neurons. Moreover, depletion OGD/R treated N2a mitigated protective effects OM-MSCs. Altogether, exerted probably via modulating reducing

Language: Английский

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Bone Marrow Mesenchymal Stem Cells Exert Protective Effects After Ischemic Stroke Through Upregulation of Glutathione

Stem Cell Reviews and Reports, Journal Year: 2021, Volume and Issue: 18(2), P. 585 - 594

Published: Aug. 27, 2021

Language: Английский

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