The Effects of Cannabinoids on Ischemic Stroke-Associated Neuroinflammation: A Systematic Review

Journal of Neuroimmune Pharmacology, Journal Year: 2025, Volume and Issue: 20(1)

Published: Feb. 3, 2025

Stroke represents a significant burden on global health and the economy, with high mortality rates, disability, recurrence. Ischemic stroke is serious condition that occurs when blood vessel in brain interrupted, reducing supply to affected area. Inflammation component pathophysiology. Neuroinflammation triggered following acute ischemic ictus, where blood–brain barrier (BBB) breaks down, causing damage endothelial cells. The will eventually generate oxidative stress, activate pathological phenotypes of astrocytes microglia, lead neuronal death neurovascular unit. As result, unleashes robust neuroinflammatory response, which can further worsen neurological outcomes. complex process involved repair. Finding new neuroinflammation molecular targets essential develop effective safe novel treatment approaches against stroke. Accumulating studies have investigated pharmacological properties cannabinoids (CBs) for many years, recent research has shown their potential therapeutic use treating rodent models. These findings revealed promising impacts CBs cellular ameliorating deficits. In this review, we explore possibility administration mitigating caused by We summarize results from several preclinical evaluating efficacy anti-inflammatory interventions Although convincing evidence implies targeting are stroke, translating these into clinical setting proven be challenging. translation hurdle due essence ability cause anxiety, cognitive deficit, psychosis. Future warranted address dose-beneficial effect trials stroke-related treatment.

Language: Английский

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Nanoparticles for Thrombolytic Therapy in Ischemic Stroke: A Systematic Review and Meta-Analysis of Preclinical Studies

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(2), P. 208 - 208

Published: Feb. 6, 2025

Background: Recombinant tissue plasminogen activator (rtPA) remains the standard thrombolytic treatment for ischemic stroke. Different types of nanoparticles have emerged as promising tools to improve benefits and decrease drawbacks this therapy. Among them, cell membrane-derived (CMD) nanomedicines gained special interest due their capability increase half-life particles in blood, biocompatibility, thrombus targeting. In order update evaluate efficacy these nanosystems, we performed a meta-analysis selected vivo preclinical studies. Methods: Preclinical studies stroke models been identified through search Pubmed database. We included rtPA-nanoparticles, which assessed infarct volume and/or neurological improvement. Nanosystems were compared with free (non-encapsulated) rtPA treatment. Standardized mean differences computed pooled estimate effect sizes lesion volumes scores. Subgroup analyses by risk bias, type nanoparticle, time administration also performed. Results: A total 18 publications meta-analysis. This was based on defined inclusion criteria. Our analysis revealed that rtPA-nanoparticles improved both scores Moreover, CMD showed better evolution other nanoparticles. Funnel plots exhibited asymmetry publication bias. Heterogeneity generally high, funnel plot Egger test some evidence bias did not achieve statistical significance trim-and-fill analysis. Conclusions: rtPA-encapsulating nanosystems shown scales treatment, had greatest beneficial effect.

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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Peptidase neurolysin functions to preserve the brain after ischemic stroke in male mice

Journal of Neurochemistry, Journal Year: 2019, Volume and Issue: 153(1), P. 120 - 137

Published: Sept. 5, 2019

Abstract Previous studies documented up‐regulation of peptidase neurolysin (Nln) after brain ischemia, however, the significance Nln function in post‐stroke remained unknown. The aim this study was to assess functional role ischemic stroke. Administration a specific inhibitor Agaricoglyceride A (AgaA) mice stroke middle cerebral artery occlusion model, dose‐dependently aggravated injury measured by increased infarct and edema volumes, blood–brain barrier disruption, levels interleukin 6 monocyte chemoattractant protein‐1, neurological motor deficit 24 h In setting, AgaA resulted inhibition hemisphere leading substrates bradykinin, neurotensin, substance P. lacked effects on several physiological parameters appeared non‐toxic mice. reverse approach, we developed an adeno‐associated viral vector (AAV2/5‐CAG‐Nln) overexpress mouse brain. Applicability AAV2/5‐CAG‐Nln transduce catalytically active confirmed primary neurons vivo . Over‐expression also accompanied decreased its substrates. Two weeks transduction using AAV vector, were subjected same outcome measures evaluated 72 later. These experiments revealed that abundance protects animals from This is first document pathophysiology provide evidence endogenous mechanism functioning preserve injury. image

Language: Английский

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Delayed atomoxetine or fluoxetine treatment coupled with limited voluntary running promotes motor recovery in mice after ischemic stroke

Neural Regeneration Research, Journal Year: 2020, Volume and Issue: 16(7), P. 1244 - 1244

Published: Dec. 17, 2020

Currently, there is an unmet need for treatments promoting post-stroke functional recovery. The aim of this study was to evaluate and compare the dose-dependent effect delayed atomoxetine or fluoxetine therapy (starting on day 5), coupled with limited physical exercise (2 hours daily voluntary wheel running; days 9 42), motor recovery adult male mice after photothrombotic stroke. These drugs are selective norepinephrine serotonin reuptake inhibitors indicated disorders unrelated predetermined primary end-point function measured in two tasks spontaneous behaviors grid-walking cylinder tests. Additionally, we quantified running distance speed throughout study, number parvalbumin-positive neurons medial agranular cortex infarct volumes. Both sensorimotor tests revealed that neither nor a drug treatment alone significantly facilitated However, combination either promoted restoration by 42 post-stroke, being more potent drug. This accompanied significant decrease inhibitory interneurons ipsilateral recovering function, while volumes were comparable among experimental groups. If further validated larger studies, our observations suggest add-on limited, structured rehabilitation could offer therapeutic modality stroke survivors who have difficulty engage early, high-intensity physiotherapy. Furthermore, light recently completed Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) Efficacy Fluoxetine-a randomisEd Controlled Trial Stroke (EFFECTS) trials, call newly designed studies where pharmacotherapy evaluated rather than alone. approved Texas Tech University Health Sciences Center Institutional Animal Care Use Committee (protocol # 16019).

Language: Английский

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The role of peptidase neurolysin in neuroprotection and neural repair after stroke

Neural Regeneration Research, Journal Year: 2020, Volume and Issue: 16(1), P. 21 - 21

Published: Aug. 10, 2020

Current experimental stroke research has evolved to focus on detailed understanding of the brain's self-protective and restorative mechanisms, harness this knowledge for development new therapies. In context, role peptidases neuropeptides is growing interest. focused review, peptidase neurolysin (Nln) its extracellular peptide substrates are briefly discussed in relation pathophysiology ischemic stroke. Upregulation Nln following viewed as a compensatory cerebroprotective mechanism acute phase stroke, because main inactivated by neuro/cerebrotoxic (bradykinin, substance P, neurotensin, angiotensin II, hemopressin), whereas peptides generated neuro/cerebroprotective (angiotensin-(1–7), Leu-/Met-enkephalins). This notion confirmed studies documenting aggravation outcomes mice after inhibition dramatic improvement overexpressing brain. The (sub)chronic less clear it likely, that does not have major neural repair mechanisms. because, uniform modulating neurorestorative mechanisms one direction, some appearing enhancing/stimulating potential, others doing opposite. Future focusing should determine potential target therapy, unique ability modulate multiple neuropeptide systems critically involved brain injury likely advantageous over modulation pathogenic pathway pharmacotherapy.

Language: Английский

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Stroke and Translational Research – Review of Experimental Models with a Focus on Awake Ischaemic Induction and Anaesthesia

Neuroscience, Journal Year: 2024, Volume and Issue: 550, P. 89 - 101

Published: July 1, 2024

Animal models are an indispensable tool in the study of ischaemic stroke with hundreds drugs emerging from preclinical pipeline. However, all these have failed to translate into successful treatments clinic. This has brought focus need enhance studies improve translation. The confounding effects anaesthesia on modelling been raised as important consideration. Various volatile and injectable anaesthetics used during induction for outcome measurements such imaging or electrophysiology. modulate several pathways essential pathophysiology a dose drug dependent manner. Most notably, significant modulatory cerebral blood flow, metabolism, spreading depolarizations, neurovascular coupling. To minimise anaesthetic complications translational relevance, awake attempted limited models. review outlines strategies employed rodent their reported effects. Stroke related also addressed infarct volume, neurological deficits, thrombolysis efficacy. We summarise routinely focal discuss attempts induce some rodents.

Language: Английский

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Delayed Exercise-induced Upregulation of Angiogenic Proteins and Recovery of Motor Function after Photothrombotic Stroke in Mice

Neuroscience, Journal Year: 2021, Volume and Issue: 461, P. 57 - 71

Published: March 2, 2021

Language: Английский

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Vitamin D serum level predicts stroke clinical severity, functional independence, and disability—A retrospective cohort study

Frontiers in Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: July 27, 2022

Background Stroke is a leading cause of mortality and disability one the most common neurological conditions globally. Many studies focused on vitamin D as stroke risk factor, but only few its serum level predictor initial clinical severity recovery with inconsistent results. The purpose this study was to assess relationship between levels at admission functional independence discharge in Saudi Arabia. Methodology A retrospective cohort adult ischemic patients who had their tested admitted within 7 days exhibiting symptoms King Abdulaziz Medical City (KAMC) Jeddah, Based level, were categorized into normal [25(OH)D ≥ 75 nmol/L], insufficient 50–75 deficient ≤ 50 nmol/L]. primary outcome patients’ discharge. National Institute Health Scale (NIHSS) used severity, whereas modified Rankin scale (mRS) disability. Results included 294 patients, out 774, selected based inclusion exclusion criteria. mean age participants 68.2 ± 13.4 years, 49.3% male. distribution among three groups is: ( n = 35, 11.9%), 66, 22.5%), 196, 65.6%). After adjusting for potential covariates, regression analysis found significant inverse NIHSS 25(OH)D (beta coefficient: −0.04, SE: 0.01, p 0.003). Patients also significantly higher odds worse mRS score [OR: 2.41, 95%CI: (1.13–5.16), 0.023] when compared level. Conclusion Low associated poor acute stroke. Further randomized interventional are required confirm our findings.

Language: Английский

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The Finer Aspects of Grid-Walking and Cylinder Tests for Experimental Stroke Recovery Studies in Mice

Methods in molecular biology, Journal Year: 2023, Volume and Issue: unknown, P. 345 - 353

Published: Jan. 1, 2023

Language: Английский

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