Current neurovascular research最新文献

Stroke is associated with a high rate of long-term disability, with motor and sensory impairments of the limbs being among the most common sequelae. Conventional treatments often show limited effectiveness in fully restoring function and may lead to persistent or irreversible deficits over time. Extracorporeal shock wave therapy (ESWT), a non-invasive therapeutic modality, has emerged as a potentially effective intervention for improving motor function after stroke. Its primary therapeutic actions include enhancing blood and lymphatic circulation in the affected limbs, promoting cellular repair, relieving pain, increasing joint range of motion, reducing pathological muscle spasms, strengthening connective tissue, and mitigating abnormal tissue calcification. Given these effects, ESWT may provide direct therapeutic benefits for patients with post-stroke limb dysfunction, with reported outcomes such as pain reduction, increased pain threshold, improved sensory function, decreased abnormal muscle tone, and enhanced overall motor ability. Therefore, this article reviews current research on ESWT for post-stroke motor dysfunction, aiming to explore its therapeutic mechanisms and provide evidence-based insights to support motor function rehabilitation after stroke.

Brain injury is a leading cause of mortality and long-term disability worldwide, characterized by energy metabolism dysfunction, oxidative stress, inflammatory responses, and programmed cell death, with mitochondrial dysfunction serving as a central pathological nexus. In recent years, hydrogen, as an emerging gaseous signaling molecule, has demonstrated remarkable neuroprotective effects in various experimental models of brain injury owing to its unique biological properties, including selective antioxidant, anti-inflammatory, anti-apoptotic, and mitochondrial- protective activities. This review comprehensively summarizes the protective effects and underlying molecular mechanisms of hydrogen in ischemic stroke, traumatic brain injury, hypoxic-ischemic encephalopathy, intracerebral hemorrhage, subarachnoid hemorrhage, chronic cerebral hypoperfusion, and toxic encephalopathy. Special emphasis is placed on hydrogen's ability to modulate mitochondrial quality control networks, encompassing antioxidative membrane protection, precise regulation of mitophagy, remodeling of mitochondrial dynamics, and metabolic reprogramming, thereby improving neuronal survival and functional recovery. Moreover, this review has discussed current limitations, unresolved scientific questions, and major challenges, while proposing future directions, such as multi-omics integration, advanced structural biology investigations, innovative experimental model optimization, and systematic clinical translational research. Collectively, hydrogen holds great promise as a novel mitochondriatargeted neuroprotective strategy for brain injury, offering not only a solid theoretical foundation but also a potential personalized and precise therapeutic avenue for future clinical applications in neurological disorders.

Introduction: Neuropathic pain (NP), a chronic and debilitating condition resulting from nerve injury, remains a significant clinical challenge due to limited effective therapies. Ethyl gallate (EG), a natural ester of gallic acid, possesses potent antioxidant and antiinflammatory properties; however, its role in NP management has not been previously explored.

Methods: This study investigated the neuroprotective potential of EG in a chronic constriction injury (CCI)-induced NP model in rats. EG was administered intraperitoneally at doses of 10, 15, and 20 mg/kg/day for 14 days. Behavioral assessments, including thermal hyperalgesia, mechanical allodynia, and motor nerve conduction velocity (MNCV), were performed. Biochemical evaluations, such as oxidative stress markers (SOD, GSH, catalase, MDA) and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) were conducted. Histopathological analysis of the sciatic nerve was performed to assess structural integrity. Additionally, molecular docking was employed to evaluate the binding interactions of EG with key redox and inflammatory regulators, Nrf2 and NF-κB, in comparison with the standard drug gabapentin (GBP).

Results: EG significantly alleviated CCI-induced pain behaviors, demonstrated by increased paw withdrawal latency, enhanced mechanical threshold, and improved MNCV. EG treatment restored antioxidant enzyme activities and reduced MDA levels, indicating decreased oxidative stress. Additionally, EG markedly lowered pro-inflammatory cytokine levels. Histological findings revealed preserved nerve fiber integrity and reduced structural damage in EG-treated groups. Molecular docking revealed stronger binding affinity of EG (-6.8 kcal/mol with Nrf2; -5.1 kcal/mol with NF-κB) compared to GBP (-5.9 kcal/mol and -4.3 kcal/mol, respectively), supporting its potential mechanistic role in modulating oxidative stress and inflammatory pathways.

Discussion: These results suggest that EG mitigates NP symptoms by modulating oxidative stress and inflammation. Its ability to enhance endogenous antioxidant defenses and suppress pro-inflammatory responses underlies its neuroprotective action.

Conclusion: EG demonstrates promising therapeutic potential in the management of NP through its antioxidant, anti-inflammatory, and neuroprotective properties. Further molecular studies are warranted to elucidate its underlying mechanisms.

Introduction: Cerebral ischemia-reperfusion injury (CIRI) poses a significant challenge in the treatment of ischemic stroke. Dibutyryl cyclic AMP (dBcAMP), a cell-permeable cAMP analog, has previously been shown to exert therapeutic effects in CIRI, indicating its neuroprotective potential. However, its underlying mechanisms remain incompletely understood.

Methods: We employed an integrated approach. First, an unbiased RNA-sequencing analysis of hippocampal tissues from a murine model of CIRI (induced by unilateral common carotid artery occlusion, UCCAO) was conducted to generate hypotheses. Subsequently, the hypothesis was functionally assessed in vitro using HT22 hippocampal neuronal cells subjected to oxygenglucose deprivation/reperfusion (OGD/R). Key features of cuproptosis, including intracellular copper accumulation, mitochondrial membrane potential, and cell viability, were assessed.

Results: Transcriptomics revealed significant suppression of the cuproptosis pathway by dBcAMP. Functional experiments confirmed that dBcAMP treatment significantly reduced OGD/R-induced intracellular copper accumulation (p < 0.05), restored mitochondrial membrane potential (p < 0.05), and improved neuronal survival (p < 0.05).

Discussion: These integrated findings suggest that dBcAMP may attenuate CIRI, at least in part, by inhibiting cuproptosis-a newly defined copper-dependent cell death pathway. This preliminary evidence positions dBcAMP as a potential modulator of cuproptosis, revealing a therapeutic dimension beyond classical programmed cell death.

Conclusion: This study provides initial evidence that dBcAMP-mediated neuroprotection involves the reduction of intracellular copper overload and preservation of mitochondrial integrity, pointing to cuproptosis inhibition as a promising mechanism for future therapeutic exploration.

Introduction: Dizziness is one of the most common symptoms in elderly patients. In this study, we investigated changes in white matter fiber bundles in elderly patients with chronic dizziness using Automated Fiber Quantification (AFQ) to explore correlations with clinical manifestations and to provide novel insights for diagnosis.

Methods: This prospective study consecutively enrolled patients aged ≥60 years with varying degrees of white matter hyperintensities (WMH) on cranial MRI from May 2023 to October 2024. Participants were divided into a dizziness group and a non-dizziness group. Clinical data were collected for both cohorts. WMH severity and distribution were graded using the Fazekas scale, while AFQ tracked 18 cerebral white matter tracts. Between-group differences in fractional anisotropy (FA) and mean diffusivity (MD) were analyzed using independent samples t-tests.

Results: A total of 42 elderly patients were enrolled, including 24 in the dizziness group (mean age: 65.71 ± 5.46 years; 12 males, 50.0%) and 18 in the non-dizziness group (mean age: 65.56 ± 4.49 years; 7 males, 38.9%). Multivariate logistic regression revealed a significant association between deep white matter hyperintensities (DWMH) and chronic unexplained dizziness (OR = 8.285, 95% CI = 1.355-50.636, p = 0.022). AFQ demonstrated significantly reduced FA in the dizziness group within the left corticospinal tract, the greater occipital fasciculus, the left inferior fronto- occipital fasciculus, and the left arcuate fasciculus (p < 0.01). Conversely, MD was elevated in the left corticospinal tract, the large callosal clamp, the left and right inferior fronto-occipital fasciculi, the left superior longitudinal fasciculus, and the right arcuate fasciculus (p < 0.01).

Discussion: Our findings highlight that DWMH are closely linked to chronic dizziness in the elderly, and AFQ enables precise localization of microstructural damage in specific white matter tracts. These neuroimaging findings provide novel insights into the pathological mechanisms underlying chronic dizziness and offer potential imaging markers for clinical diagnosis. However, the cross-sectional design and single-center sample limit the generalization of the results, emphasizing the need for further multicenter longitudinal studies.

Conclusion: DWMH correlates with chronic dizziness in elderly patients. AFQ can identify the degree and location of white matter microstructural damage, providing new insights for clinical diagnosis and treatment.

This article has been retracted at the request of the author(s) from the journal Current Neurovascular Research. The authors informed the journal after publication that the animal experiments reported in the study were conducted without prior approval from the institutional Animal Ethics Committee, and that the required ethical approval documentation had not been obtained at the time of submission. In fact, at the time of submission, the author(s) declared that the required permission was obtained before proceeding for publication. The publisher cannot decide which statement of authors(s) is correct. The author(s) acknowledged that this omission occurred due to inexperience and an unintended oversight during the submission process. Following publication, concerns were raised by the authors' colleagues, the institutional ethics committee, and the relevant Science and Education department regarding the absence of formal ethical approval. In view of these concerns, the authors formally requested retraction of the article and expressed their apologies to the journal and its readership. As adherence to ethical standards for animal research is mandatory for publication, the Publisher has decided to retract the article in order to maintain the integrity of the scientific record. The publisher apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php. BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure, or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication, the authors agree that the publishers have the legal right to take appropriate action against the authors if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Introduction: Stroke is a leading cause of death and disability globally, influenced by genetic, environmental, and metabolic factors. Although cerebrospinal fluid (CSF) metabolites are closely linked to stroke, their causal roles remain unclear.

Methods: We integrated genome-wide association study (GWAS) data on 338 CSF metabolites with stroke outcomes. Two-sample and reverse Mendelian randomization (MR) analyses were conducted to assess causal associations between metabolites and stroke, including its subtypes: ischemic stroke, cardioembolic stroke, large artery stroke, and small vessel stroke. Seven complementary MR methods, including inverse variance weighted (IVW), were applied to evaluate pleiotropy and heterogeneity, ensuring robust causal inference.

Results: Eighteen CSF metabolites showed significant associations with overall stroke, including six risk factors (e.g., creatinine; OR = 1.390, 95% CI: 1.167-1.656) and twelve protective factors (e.g., β-citrylglutamate; OR = 0.899, 95% CI: 0.827-0.977). Subtype analyses identified 14 metabolites linked to ischemic stroke, 31 to cardioembolic stroke, 6 to large artery stroke, and 19 to small vessel stroke. Reverse MR revealed that stroke causally influenced 9 metabolites, such as increased N-acetyltaurine (OR = 1.105) and decreased succinimide (OR = 0.814). Sensitivity analyses confirmed the robustness of these findings.

Discussion: Our study provides evidence that specific CSF metabolites play causal roles in different stroke subtypes and that stroke itself can alter CSF metabolic profiles, suggesting bidirectional interactions.

Conclusion: This work reveals novel mechanistic insights and identifies potential biomarkers and therapeutic targets for stroke diagnosis and precision medicine.

Introduction: To delineate the distinct immunoregulatory and mitochondrial characteristics in patients with acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH).

Methods: We conducted a cross-sectional study (34 AIS, 27 ICH, 30 controls) and a dynamic tracking study (1 AIS, 1 ICH). T-cell subpopulations, mitochondrial mass (MM), low mitochondrial membrane potential (MMPlow, %), and cytokine profiles were analyzed. Limitations include the small dynamic cohort and potential treatment-related confounding.

Results: The percentages of T regulatory lymphocytes (Treg%) and effector T regulatory lymphocytes (eTreg%) were significantly higher in AIS patients than in ICH patients (p = 0.029, p = 0.017) and correlated with disease severity in AIS patients (p = 0.024, p = 0.014). The IL-10/IL-6 ratio was significantly higher in AIS than in ICH patients (p = 0.004). AIS patients exhibited predominant changes in CD4+ (T4) lymphocyte subsets, whereas ICH patients showed more pronounced alterations in CD8+ (T8) subsets, with corresponding mitochondrial damage observed in T-cells in both groups.

Discussion: Despite limitations from the small dynamic cohort and inherent clinical confounders, this study demonstrates that AIS and ICH are characterized by distinct and evolving immune- inflammatory-mitochondrial axes. These preliminary findings highlight the role of Treg cells in AIS and suggest divergent T-cell subset involvement, providing a rationale for developing subtype-specific therapeutic strategies targeting the immune-mitochondrial axis.

Conclusion: Our study delineates a distinct immune-inflammatory-mitochondrial axis in stroke, characterized by predominant CD4+ involvement in AIS versus CD8+ T-cell alterations in ICH. These findings underscore the potential for immunomodulatory and mitochondrial-protective strategies tailored to specific stroke subtypes.

The PI3K/AKT and Nrf2 signaling systems are essential for neurogenesis, synaptic plasticity, and cellular survival, and their dysregulation has been linked to the progression of Alzheimer's disease (AD). Due to its complex pathophysiology, currently approved therapeutic agents only provide symptomatic relief and are often associated with serious side effects. Researchers have increasingly focused on natural bioactive compounds as potential therapies, with flavonoids emerging as promising candidates due to their diverse neuroprotective properties. These polyphenolic compounds exhibit notable anti-inflammatory, anti-apoptotic, and antioxidant effects, making them attractive therapeutic agents against AD. A key mechanism by which flavonoids exert neuroprotection is through modulation of the PI3K/AKT and Nrf2 signaling pathways. By enhancing neuronal resilience, reducing oxidative stress, inhibiting apoptosis, and regulating autophagy, flavonoids can mitigate neurodegenerative processes associated with AD. Additionally, they attenuate Aβ accumulation and tau hyperphosphorylation, both of which contribute to neuronal dysfunction, via PI3K/AKT activation and Nrf2 pathway regulation. In preclinical AD models, numerous flavonoids-including epicatechin, kaempferol, quercetin, and luteolin- have demonstrated neuroprotective effects through regulation of the PI3K/AKT and Nrf2 pathways. Despite these encouraging findings, further research is needed to determine optimal dosages, strategies for enhancing bioavailability, and the long-term effects of flavonoid-based therapies in AD. Future studies should focus on translating preclinical evidence into clinical trials, which could improve patient outcomes and quality of life. A deeper understanding of the molecular mechanisms underlying flavonoid activity, particularly their interaction with PI3K/AKT and Nrf2 pathways, may pave the way for novel neuroprotective therapies.

Introduction: Neuroinflammation is recognized as one of the pathogenic mechanisms underlying sepsis-associated encephalopathy (SAE). As the most commonly used anesthetic agent in the perioperative period, propofol has been demonstrated to exhibit neuroprotective and anti-inflammatory effects. This study aimed to investigate whether propofol could mitigate lipopolysaccharide (LPS)-mediated neuroinflammation and to explore the potential mechanisms.

Methods: hCMEC/D3 cells were treated with propofol, followed by LPS exposure. Western blot, ELISA, and RT-qPCR were used to assess the expression (both protein and mRNA levels) of potential pathway participants. Intracellular Fe2+ levels were determined using an Iron Assay Kit. In addition, an in vitro blood-brain barrier (BBB) model was constructed by co-culturing hCMEC/D3 cells and human astrocytes, and BBB permeability was assessed by measuring trans-endothelial electrical resistance (TEER).

Results: LPS (50 μg/mL, 1 h) significantly increased the secretion of TNF-α and IL-1β, induced intracellular Fe2+ accumulation, and upregulated the expression of 4-HNE, H3K18la, pan-Kla, and LDHA, while decreasing the expression of ZO-1, Claudin-5, and Occludin in hCMEC/D3 cells. More importantly, propofol (25 μM, 2 h) alleviated the aforementioned effects of LPS on hCMEC/D3 cells. Furthermore, we observed significant LPS-induced TEER reduction in the in vitro BBB model, and this effect was attenuated by propofol pretreatment.

Discussion: The protective effect of propofol on hCMEC/D3 cells' ferroptosis and LDHAlactylation induced by LPS may be an important mechanism for neuroinflammation.

Conclusion: Propofol inhibits LPS-induced lactylation, ferroptosis, and release of inflammatory cytokines in hCMEC/D3 cells by downregulating the expression of LDHA.