Neuroprotective Effects of Metformin in Stroke Patients: A Systematic Review and Meta-analysis of Cohort Studies DOI
Mohammad Mohammadi, Sadaf Salehi, Adrina Habibzadeh

et al.

Clinical Neuropharmacology, Journal Year: 2025, Volume and Issue: 48(2), P. 51 - 59

Published: March 1, 2025

Objectives People with diabetes are 1.5 times more likely to experience stroke than those without diabetes, underlining the urgent need address this issue. Metformin is often initial medication chosen manage mellitus (DM). The purpose of our systematic review and meta-analysis explore potential neuroprotective effects metformin in individuals who have received it prior stroke. Method Our study encompassed cohort studies that drew a comparison between severity diverse outcomes among DM were administered event did not receive treatment. Results Ten met eligibility criteria. Prestroke use was associated significantly lower National Institutes Health Stroke Scale score (mean difference = −1.29, 95% confidence interval: −2.11 −0.47) ischemic pretreatment increased odds favorable outcome (mRS < 2) at 90 days (odds ratio [OR] 1.45, interval [CI]: 1.06 1.99), but significant discharge. found be reduced mortality (OR 0.52, CI: 0.42 0.64) In hemorrhagic stroke, results showed intracranial hemorrhage volume prestroke −4.77, −6.56 −2.98). Conclusions We diabetic patients yielded effects. strokes, reduces 90-day mortality; also improves functional outcomes. can cause less volume. Further clinical trials needed confirm its efficacy verify benefits management.

Language: Английский

Advances in Therapies to Treat Neonatal Hypoxic-Ischemic Encephalopathy DOI Open Access
Amaresh K. Ranjan, Anil Gulati

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(20), P. 6653 - 6653

Published: Oct. 20, 2023

Neonatal hypoxic-ischemic encephalopathy (HIE) is a condition that results in brain damage newborns due to insufficient blood and oxygen supply during or after birth. HIE major cause of neurological disability mortality newborns, with over one million neonatal deaths occurring annually worldwide. The severity injury the outcome depend on several factors, including deprivation, maturity, regional flow, maternal health conditions. classified into mild, moderate, severe categories based extent resulting issues. pathophysiology involves different phases, primary phase, latent secondary tertiary phase. phases are characterized by episodes energy cell metabolism failures, increased cytotoxicity apoptosis, activated microglia inflammation brain. A phase occurs if persists, reduced neural plasticity neuronal loss. Understanding cellular molecular aspects crucial for developing new interventions therapeutics. This review aims discuss HIE, therapeutic hypothermia (TH), only approved therapy ongoing developments adjuvants TH, potential future drugs HIE.

Language: Английский

Citations

34
Metformin alleviates cerebral ischemia/reperfusion injury aggravated by hyperglycemia via regulating AMPK/ULK1/PINK1/Parkin pathway-mediated mitophagy and apoptosis DOI
Yaqi Guo, Haifeng Jiang, Meng Wang

et al.

Chemico-Biological Interactions, Journal Year: 2023, Volume and Issue: 384, P. 110723 - 110723

Published: Sept. 21, 2023

Language: Английский

Citations

31
SGLT2 inhibitors: a novel therapy for cognitive impairment via multifaceted effects on the nervous system DOI Creative Commons
Jiaqi Mei,

Yi Li,

Liyan Niu

et al.

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: Aug. 9, 2024

The rising prevalence of diabetes mellitus has casted a spotlight on one its significant sequelae: cognitive impairment. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally developed for management, are increasingly studied their benefits. These benefits may include reduction oxidative stress and neuroinflammation, decrease amyloid burdens, enhancement neuronal plasticity, improved cerebral glucose utilization. multifaceted effects the relatively favorable side-effect profile SGLT2 inhibitors render them promising therapeutic candidate disorders. Nonetheless, application impairment is not without limitations, necessitating more comprehensive research to fully determine potential treatment. In this review, we discuss role in neural function, elucidate diabetes-cognition nexus, synthesize current knowledge based animal studies clinical evidence. Research gaps proposed spur further investigation.

Language: Английский

Citations

15
Role of glucagon-like peptide-1 receptor agonists in Alzheimer’s disease and Parkinson’s disease DOI Creative Commons

Chien‐Tai Hong,

Jia‐Hung Chen,

Chaur‐Jong Hu

et al.

Journal of Biomedical Science, Journal Year: 2024, Volume and Issue: 31(1)

Published: Nov. 5, 2024

Abstract Neurodegenerative diseases, including Alzheimer’s Disease (AD) and Parkinson’s (PD) are common complications of diabetes, arising from insulin resistance, inflammation, other pathological processes in the central nervous system. The potential numerous antidiabetic agents to modify neurodegenerative disease progression, both preclinically clinically, has been assessed. These may provide additional therapeutic benefits beyond glycemic control. Introduced twenty-first century, glucagon-like peptide-1 receptor agonists (GLP-1RAs) a class drugs noted not only for their potent glucose-lowering effects but also cardiovascular renal protective benefits. Various GLP-1RAs have demonstrated significant vitro vivo models diseases through modulating variety pathogenic mechanisms, neuroinflammation, autophagy, mitochondrial dysfunction, abnormal phosphorylation pathognomonic proteins. substantial on cognitive behavioral functions, such as motor function. However, clinical trials investigating AD, PD, mild impairment, psychiatric disorders, diabetes yielded mixed results This review examines link between explores neurodegeneration, provides concise overview GLP-1 pathway, discusses preclinical trial outcomes cognition AD PD. proposed new strategies design future RAs

Language: Английский

Citations

14
Identification of Parkinson’s disease PACE subtypes and repurposing treatments through integrative analyses of multimodal data DOI Creative Commons
Chang Su,

Yu Hou,

Jielin Xu

et al.

npj Digital Medicine, Journal Year: 2024, Volume and Issue: 7(1)

Published: July 9, 2024

Abstract Parkinson’s disease (PD) is a serious neurodegenerative disorder marked by significant clinical and progression heterogeneity. This study aimed at addressing heterogeneity of PD through integrative analysis various data modalities. We analyzed (≥5 years) individuals with de novo using machine learning deep learning, to characterize individuals’ phenotypic trajectories for subtyping. discovered three pace subtypes exhibiting distinct patterns: the Inching Pace subtype (PD-I) mild baseline severity speed; Moderate (PD-M) but advancing moderate rate; Rapid (PD-R) most rapid symptom rate. found cerebrospinal fluid P-tau/α-synuclein ratio atrophy in certain brain regions as potential markers these subtypes. Analyses genetic transcriptomic profiles network-based approaches identified molecular modules associated each subtype. For instance, PD-R-specific module suggested STAT3 , FYN BECN1 APOA1 NEDD4 GATA2 driver genes PD-R. It also neuroinflammation, oxidative stress, metabolism, PI3K/AKT, angiogenesis pathways drivers (i.e., PD-R). Moreover, we repurposable drug candidates targeting subtype-specific approach cell line drug-gene signature data. further estimated their treatment effects two large-scale real-world patient databases; evidence gained highlighted metformin ameliorating progression. In conclusion, this work helps better understand pathophysiological complexity accelerate precision medicine.

Language: Английский

Citations

10
A metformin add-on clinical study in multiple sclerosis to evaluate brain remyelination and neurodegeneration (MACSiMiSE-BRAIN): study protocol for a multi-center randomized placebo controlled clinical trial DOI Creative Commons

Anna-Victoria De Keersmaecker,

Eline Van Doninck,

Veronica Popescu

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 21, 2024

Introduction Despite advances in immunomodulatory treatments of multiple sclerosis (MS), patients with non-active progressive (PMS) continue to face a significant unmet need. Demyelination, smoldering inflammation and neurodegeneration are important drivers disability progression that insufficiently targeted by current treatment approaches. Promising preclinical data support repurposing metformin for PMS. The objective this clinical trial is evaluate whether metformin, as add-on treatment, superior placebo delaying disease Methods analysis MACSiMiSE-BRAIN multi-center two-arm, 1:1 randomized, triple-blind, placebo-controlled trial, conducted at five sites Belgium. Enrollment 120 PMS planned. Each participant will undergo screening visit assessment baseline magnetic resonance imaging (MRI), tests, questionnaires, safety laboratory assessment. Following randomization, participants be assigned either the (metformin) or group. Subsequently, they 96-week follow-up period. primary outcome change walking speed, measured Timed 25-Foot Walk Test, from 96 weeks. Secondary measures include neurological (Expanded Disability Status Score), information processing speed (Symbol Digit Modalities Test) hand function (9-Hole Peg test). Annual brain MRI performed assess evolution volumetry diffusion metrics. As may not progress all domains, composite outcome, Overall Response Score additionally evaluated an exploratory outcome. Other outcomes consist paramagnetic rim lesions, 2-minute test health economic analyses well both patient- caregiver-reported like EQ-5D-5L, Multiple Sclerosis Impact Scale Caregiver Strain Index. Ethics dissemination Clinical authorization regulatory agencies [Ethical Committee Federal Agency Medicines Health Products (FAMHP)] was obtained after submission centralized European Trial Information System. results disseminated scientific conferences, peer-reviewed publications, patient associations general public. registration ClinicalTrials.gov Identifier: NCT05893225, EUCT number: 2023-503190-38-00.

Language: Английский

Citations

9
Metformin’s Effects on Cognitive Function from a Biovariance Perspective: A Narrative Review DOI Open Access

Dimitrie Chele,

Carmen Adella Sîrbu,

Marian Mitrică

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1783 - 1783

Published: Feb. 19, 2025

This study examines the effects of metformin on brain functions focusing variability results reported in literature. While some studies suggest that may have neuroprotective diabetic patients, others report an insignificant impact cognitive function, or even a negative effect. We propose this inconsistency be due to intrinsic cellular-level among individuals, which we term "biovariance". Biovariance persists demographically homogeneous samples complex and stochastic biological processes. Additionally, metabolic actions metformin, including its influence neuroenergetics neuronal survival, produce different depending individual characteristics.

Language: Английский

Citations

1
Brain insulin signaling as a potential mediator of early life adversity effects on physical and mental health DOI Creative Commons
Bonnie Alberry, Patrícia Pelufo Silveira

Neuroscience & Biobehavioral Reviews, Journal Year: 2023, Volume and Issue: 153, P. 105350 - 105350

Published: Aug. 6, 2023

In numerous brain structures, insulin signaling modulates the homeostatic processes, sensitivity to reward pathways, executive function, memory, and cognition. Through human studies animal models, mounting evidence implicates central in metabolic, physiological, psychological consequences of early life adversity. this review, we describe adversity where is a key factor how may moderate effects on psychiatric cardio-metabolic health outcomes. Further understanding impact specific regions mental physical outcomes will assist prevention, diagnosis, potential intervention following

Language: Английский

Citations

18
Autophagy modulation in cancer therapy: Challenges coexist with opportunities DOI
Yongya Wu,

Aoxue Wang,

Guotai Feng

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 276, P. 116688 - 116688

Published: July 17, 2024

Language: Английский

Citations

7
The potential effect of metformin on cognitive and other symptom dimensions in patients with schizophrenia and antipsychotic-induced weight gain: a systematic review, meta-analysis, and meta-regression DOI Creative Commons
Vera Battini, Giovanna Cirnigliaro,

Rodolfo Leuzzi

et al.

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

Published: July 12, 2023

Introduction Metformin has shown good efficacy in the management of antipsychotic-induced metabolic syndrome (MetS) patients with schizophrenia or schizoaffective disorders. Its ability to induce antidepressant behavioural effects and improve cognitive functions also been investigated: yet information not systematized. The aim this study was therefore investigate metformin on other symptom dimension schizophrenic treated antipsychotics through a systematic review meta-analysis. Methods We searched PubMed, ClinicalTrials.Gov, Embase, PsycINFO, WHO ICTRP database up February 2022, Randomised Controlled Trials (RCT) evaluating diagnosed related disorders, who were as add-on therapy for treatment weight gain which changes psychiatric symptoms evaluated. Results A total 19 RCTs met inclusion criteria. Meta-analysis performed 12 eligible studies. found positive trend after 24 weeks stable conditions [SMD (95%CI) = -0.40 (−0.82;0.01), OR 0.5 (−2.4;3.4)]. Better performance detected Brief Assessment Cognition Schizophrenia Positive Negative Syndrome Scale (PANSS) low heterogeneity among One reported BACS-verbal memory subdomain favour placebo [MD -16.03 (-23.65;8.42)]. Gastrointestinal xerostomia, extrapyramidal most adverse effects. Psychiatric events described: particular, attributable relapse schizophrenia. Conclusion Some degree improving dimensions Schizophrenia. Given clinical relevance potential pharmacological effect, longer specific studies using adequate psychometric scales are strongly recommended. Likewise, how acts context needs be evaluated order enhance its find more efficacious drugs.

Language: Английский

Citations

15