Exacerbated ischemic brain damage in type 2 diabetes via methylglyoxal-mediated miR-148a-3p decline DOI Creative Commons
Zhenguo Yang, Cheng Huang, Wenhui Huang

et al.

BMC Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Nov. 26, 2024

Although microvascular dysfunction is a widespread phenomenon in type 2 diabetes (T2D) and recognized as main cause of T2D-aggravated ischemic stroke injury, the underlying mechanisms by which T2D-mediated exacerbation cerebral damage after still largely uncharacterized. Here, we found that methylglyoxal-mediated miR-148a-3p decline can trigger blood-brain barrier dysfunction, thereby exacerbating cerebrovascular injury diabetic stroke. Using T2D models generated with streptozotocin plus high-fat diet or db/db mice, then inducing focal through middle artery occlusion reperfusion (MCAO/R), established mouse model. RNA-sequencing was applied to identify differentially expressed miRNAs peri-cerebral infarction mice. RT-qPCR confirmed potential miRNA plasma patients without T2D. Fluorescence situ hybridization used image localization miRNA. Brain pathology analyzed using magnetic resonance imaging, laser-Doppler flowmetry, transmission electron microscope Immunofluorescence immunoblotting were performed elucidate molecular mechanisms. level downregulated peri-infarct cortex mice this downregulation even more enhanced A similar decrease expression also compared only. This intensified severity BBB damage, infarct size, neurological function impairment caused Notably, reduction levels primarily triggered methylglyoxal, toxic byproduct glucose metabolism commonly associated Furthermore, methylglyoxal somewhat replicated influence increasing size ischemia. Mechanistically, de-repressed SMAD2 activated matrix metalloproteinase 9 signaling pathway, promoting impairment, injury. Blood-brain may provide novel target for therapeutic intervention treatment diabetes.

Language: Английский

Therapeutic gene delivery by mesenchymal stem cell for brain ischemia damage: Focus on molecular mechanisms in ischemic stroke DOI
Raed Obaid Saleh,

Ali A. Majeed,

Ria Margiana

et al.

Cell Biochemistry and Function, Journal Year: 2024, Volume and Issue: 42(2)

Published: March 1, 2024

Abstract Cerebral ischemic damage is prevalent and the second highest cause of death globally across patient populations; it as a substantial reason morbidity mortality. Mesenchymal stromal cells (MSCs) have garnered significant interest potential treatment for cerebral damage, shown in stroke, because their potent intrinsic features, which include self‐regeneration, immunomodulation, multi‐potency. Additionally, MSCs are easily obtained, isolated, cultured. Despite this, there number obstacles that hinder effectiveness MSC‐based treatment, such adverse microenvironmental conditions both vivo vitro. To overcome these obstacles, naïve MSC has undergone modification processes to enhance its innate therapeutic qualities. Genetic preconditioning (with medications, growth factors, other substances) two main categories into techniques can be separated. This field advanced significantly still attracting attention innovation. We examine cutting‐edge methods preserving even improving natural biological functions relation adhesion, migration, homing target site, survival, delayed premature senescence. address use genetically altered stroke‐induced damage. Future strategies result addressing difficulties associated with also discussed.

Language: Английский

Citations

6
Tanshinone IIA Against Cerebral Ischemic Stroke and Ischemia- Reperfusion Injury: A Review of the Current Documents DOI
Reza Arefnezhad,

Alireza Nejabat,

Fatemeh Behjati

et al.

Mini-Reviews in Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 24(18), P. 1701 - 1709

Published: March 14, 2024

Abstract:: Stroke is a well-known neurological disorder that carries significant morbidity and mortality rates worldwide. Cerebral Ischemic (CIS), the most common subtype of stroke, occurs when thrombosis or emboli form elsewhere in body travel to brain, leading reduced blood perfusion. Ischemia/Reperfusion Injury (CIRI) complication CIS arises flow rapidly restored brain tissue after period ischemia. The therapeutic approaches currently recognized for CIS, such as thrombolysis thrombectomy, have notable side effects limit their clinical application. Recently, there has been growing interest among researchers exploring potential herbal agents treating various disorders malignancies. One agent with medicinal applications tanshinone IIA, an active diterpene quinone extracted from Salvia miltiorrhiza Bunge. Tanshinone IIA shown several pharmacological benefits, including anti-inflammatory, antioxidant, anti-apoptotic, neuroprotective properties. Multiple studies indicated protective role CIRI. This literature review aims summarize current findings regarding molecular mechanisms through which this compound improves

Language: Английский

Citations

5
The Role of microRNAs in Epigenetic Regulation of Signaling Pathways in Neurological Pathologies DOI Open Access
Pavel P. Tregub, Irada Ibrahimli, Anton S. Averchuk

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(16), P. 12899 - 12899

Published: Aug. 17, 2023

In recent times, there has been a significant increase in researchers’ interest the functions of microRNAs and role these molecules pathogenesis many multifactorial diseases. This is related to diagnostic prognostic potential microRNA expression levels as well prospects using it personalized targeted therapy. review literature analyzes existing scientific data on involvement molecular cellular mechanisms underlying development pathologies such Alzheimer’s disease, cerebral ischemia reperfusion injury, dysfunction blood–brain barrier.

Language: Английский

Citations

10
Liposome-loaded miR-34c-5p attenuates apoptosis and oxidative stress following hypoxia-ischemia brain damage in neonatal mice by targeting Arhgap26 DOI
Yan Song, Xiaohui Xing, Yilei Xiao

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177471 - 177471

Published: March 1, 2025

Language: Английский

Citations

0
Calcium/Calmodulin-Dependent Protein Kinase II β Regulates Autophagy Dependent Ferroptosis of Neurons after Cerebral Ischemic Injury by Activating the AREG/JUN/ELAVL1 Pathway DOI
Yun Du, Haiqin Wu, Shuqin Zhan

et al.

Neurochemical Research, Journal Year: 2025, Volume and Issue: 50(2)

Published: April 1, 2025

Language: Английский

Citations

0
Decreased circulating microRNA-22 expression as a potential biomarker for predicting a higher risk of recurrent ischemic stroke related to inner carotid artery stenosis: a multicenter study DOI
Wen Liu, Na Qi, Shiyan Li

et al.

Journal of Thrombosis and Thrombolysis, Journal Year: 2025, Volume and Issue: unknown

Published: May 25, 2025

Language: Английский

Citations

0
The activation of AMPK/PGC-1α/GLUT4 signaling pathway through early exercise improves mitochondrial function and mitigates ischemic brain damage DOI
Xinyue Wu, Chen Li,

Changkai Ke

et al.

Neuroreport, Journal Year: 2024, Volume and Issue: 35(10), P. 648 - 656

Published: May 15, 2024

Mitochondria play a crucial role in maintaining cellular energy supply and serve as source of for repairing nerve damage following stroke. Given that exercise has the potential to enhance metabolism, investigating impact on mitochondrial function provides plausible mechanism stroke treatment. In our study, we established middle cerebral artery occlusion (MCAO) model Sprague–Dawley rats implemented early intervention. Neurological severity scores, beam-walking test score, weight were used evaluate neurological function. The volume infarction was measured by MRI. Nerve cell apoptosis detected TUNEL staining. Mitochondrial morphology structure electron microscopy. assessed using membrane ATP measurements. Western blotting detect protein expression AMPK/PGC-1α/GLUT4. Through above experiments, found improved after MCAO, reduced neuronal apoptosis, promoted recovery We further examined AMPK/PGC-1α/GLUT4 signaling pathway confirmed able increase its expression. Therefore, suggest initiated pathway, restoring augmenting supply. This, turn, effectively both body ischemic

Language: Английский

Citations

3
GLP-1R knockdown abrogates the protective effects of liraglutide on ischaemic stroke via inhibition of M2 polarisation and activation of NLRP3 inflammasome by reducing Nrf2 activation DOI
Xian-kun Tu, Pingping Chen, Jingyi Chen

et al.

Neuropharmacology, Journal Year: 2023, Volume and Issue: 237, P. 109603 - 109603

Published: May 25, 2023

Language: Английский

Citations

6
In Vivo Experimental Models of Cerebral Ischemia: Analysis, Translational Potential and Clinical Relevance DOI Creative Commons
Lidija Radenović

Cardiology Research and Cardiovascular Medicine, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 8, 2024

Despite all current efforts in the field of cerebrovascular disease prevention, stroke remains leading cause disability and death worldwide. Animal models are essential tools research to mitigate its devastating effects. The novelty this review is comprehensiveness approach detailed analysis progress field, translational potential clinical relevance. Recent aimed refine enhance animal better mimic scenario improve reproducibility. This provides extensive overview classification, underlining their key features, advantages, limitations, advancements. Additionally, characterization validation ischemia discussed. Therapeutic strategies such as hypothermia, pharmacological interventions, genetic molecular approaches, cell-based therapies highlighted. analyse challenges future directions, well relevance models. Incorporating patient-derived cells modifications can provide a more personalized clinically relevant approach. Bridging gap challenging requires careful consideration multiple factors, including appropriate dose translation, understanding species differences, aligning protocols. Future studies should focus on optimizing process conducting well-designed trials assess safety efficacy promising interventions.

Language: Английский

Citations

2
A systematic study on key Epigenetic modulators in post-stroke conditions DOI Creative Commons
Dhruv Parikh, Manan Shah

Advances in Biomarker Sciences and Technology, Journal Year: 2024, Volume and Issue: 6, P. 120 - 137

Published: Jan. 1, 2024

A stroke is a medical emergency characterized by the sudden interruption of blood flow to brain, leading cell death from oxygen deprivation. As cause mortality and long-term disability worldwide, strokes present growing socioeconomic challenge, exacerbated demographic shifts an increasing incidence in younger populations. Analyzing post-stroke conditions essential for predicting recovery trajectories guiding personalized treatments. The process crucial mitigating cognitive deficits improving quality life survivors their families. Epigenetic mechanisms are emerging as key influencers, with four significant modulators—miRNAs, lncRNAs, DNA methylation, histone modifications—being identified central modulating neuronal repair regeneration. However, this lack knowledge how major epigenetic signatures affect recovery. paper systematically reviews capacity miRNAs fine-tune neuroprotective responses broader regulatory functions lncRNAs. Additionally, we examine methylation patterns modifications correlate outcomes, presenting case precise therapies. In review, highlight that these modulators offer promising therapeutic targets enhancing provide novel insights into pathology treatment. We also comparative analysis challenges future perspectives each one. review sets forth trajectory research, underscoring development epigenetic-based therapeutics groundbreaking approach enhance neurorehabilitation improve patient prognoses.

Language: Английский

Citations

2