Neurological Research最新文献

Objectives: Neurodevelopmental and neurodegenerative disorders arise from complex disruptions in brain structure and function, many originating during early development. However, conventional in vitro and animal models often fail to capture the cellular diversity, temporal dynamics, and architectural complexity of the human brain. This review aims to synthesize recent advances in stem-cell-derived in vitro platforms, specifically brain organoids, assembloids, and organ-on-chip technologies, and evaluate how these systems are reshaping research on Alzheimer's and Parkinson's diseases by enabling more human-relevant modeling.

Methods: We surveyed recent literature focusing on region-specific and vascularized organoids, integrated neuronal subtype models, and microfluidic organ-on-chip systems. Particular attention was given to studies demonstrating increased physiological relevance, enhanced modeling of disease-specific phenotypes, and expanding utility in translational research, therapeutic screening, and drug discovery pipelines.

Results: Innovations in organoid engineering have enabled more faithful recapitulation of human brain development and degeneration. These platforms have advanced understanding of amyloid aggregation, neuroinflammatory processes, dopaminergic neuron vulnerability, and gut-brain axis contributions. The incorporation of vascular structures, improved microfluidic control, and assembly of multi-region neuronal circuits have strengthened functional readouts and boosted mechanistic insight. Collectively, these developments are accelerating preclinical therapeutic testing and enabling more predictive disease modeling.

Discussion: Compared to prior reviews, this article uniquely integrates developmental and degenerative perspectives while evaluating emerging strategies that increase reproducibility and translational accuracy. Persistent limitations, including incomplete vascularization, cellular stress responses, and batch-to-batch variability, underscore the need for improved standardization and incorporation of immune components. Future directions that merge vascular, immune, and circuit-level complexity promise to advance organoid-based neuroscience toward personalized modeling and therapeutic application.

Background: Shifting the microglia/macrophages from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype shows promise in developing therapeutic strategies after ischemic stroke (IS). The study is aimed to investigate the role of krueppel-like factor 2 (KLF2) in modulating microglia/macrophage polarization during IS.

Methods: Mice received a 60-min middle cerebral artery occlusion (MCAO) and BV-2 cells underwent oxygen-glucose deprivation/reperfusion (OGD/R) treatment to induce IS-like injury in vivo and in vitro.

Results: The mice subjected to MCAO exhibited impaired neurobehavioral performance, lower expressions of KLF2, Nrf2 and HO-1 in the peri-infarct cortex than the sham operated mice. Lentivirus-mediated KLF2 overexpression could effectively reduce the size of brain infarct, improve the recovery of neurobehavioral functions, and activate the Nrf2-HO-1 pathway in the mice subjected to MCAO. In addition, KLF2 overexpression led to M1 suppression and increase in M2 phenotype in OGD/R-insulted BV-2 microglial cells. Nrf2 knockdown was found to impair the effects of KLF2 overexpression on status of M1 and M2 phenotypes in OGD/R-insulted BV-2 cells.

Conclusion: The study unveils KLF2 is neuroprotection and could promote microglia/macrophage polarization from the M1 to M2 phenotype in IS by activating the Nrf2-HO-1 pathway.

Background: Intracerebral hemorrhage (ICH) is a prevalent cerebrovascular event that triggers secondary brain injury in which microglial activation is central. This study explored how miR-92a-3p governs autophagy and inflammatory signaling in this context.

Methods: An in vitro ICH model was established using rat microglia exposed to hemoglobin, with lipopolysaccharide to induce autophagy. Cells were transfected with miR-92a-3p mimics or inhibitors. Apoptosis, miR-92a-3p/ATG14 expression, autophagy-related proteins (LC3, P62), and pro-inflammatory factors were assessed via molecular and cellular assays.

Results: Dual luciferase assays and ATG14 silencing confirmed direct targeting of ATG14 by miR-92a-3p. Upregulation of miR-92a-3p suppressed autophagy and thereby reduced inflammatory cytokine release, whereas inhibition of miR-92a-3p restored autophagic activity and reduced inflammation.

Conclusion: These findings establish miR-92a-3p as a critical regulator of microglial autophagy and inflammation after hemorrhagic stroke and identify it as a prospective therapeutic target for neuroinflammatory modulation.

Objectives: The accumulation of glutamate in the brain synaptosomes is called excitotoxicity which is an underlying mechanism of epilepsy. Platelets also contain a glutamate-glutamine cycle similar to the brain. Platelets release glutamate upon activation and also clear glutamate from the blood upon uptake. It was shown before that the platelet glutamate uptake is decreased in neurodegeneration. Therefore, we aimed to analyze the mRNA expression of Glutamate Transporter 1 (GLT-1), Glutamate Dehydrogenase (GDH), Glutamine Synthetase (GS) and Glutaminase, which are the modulators of glutamate metabolism, in isolated platelets from the blood of patients with temporal lobe epilepsy (TLE) or status epilepticus (SE) and healthy controls.

Methods: We isolated total RNA from the platelets of TLE, SE patients and healthy controls and then carried out quantitative PCR to analyze the gene expression.

Results: We observed that GLT-1, GS and glutaminase expressions are significantly higher and the expression of GDH is significantly lower in the platelets of patients with TLE or SE compared to healthy controls.

Discussion: We concluded that in order to clear out and metabolize the excess glutamate GLT-1, GS and glutaminase increases in TLE and SE; however since GDH expression is lower in patients, we think that excess glutamate may not be directed to Krebs cycle resulting in lower ATP production in these diseases. We showed that platelet glutamate transporters may be used as peripheral markers to investigate the role of glutamate in patients with neurological diseases.

Objectives: The diagnosis of Amyotrophic Lateral Sclerosis (ALS) can be challenging when clinical and electrophysiological findings are insufficient. We aimed to investigate the potential role of cervical Skeletal Muscle Index (SMI), as a supportive diagnostic marker in ALS, particularly in relation to disease duration.

Methods: A total of 22 ALS patients and 25 age- and sex-matched controls were retrospectively included. The cross-sectional area (CSA) of cervical muscles was measured on axial T1-weighted magnetic resonance imaging (MRI) at the C3 vertebra level. SMI was calculated by normalizing the total CSA to patient height (mm²/m²). ALS patients were stratified based on the timing of MRI: within six months of symptom onset and after six months.

Results: There were no significant differences in age, sex, BMI, or total muscle volume between patients and controls. Although mean SMI was slightly lower in ALS patients (p = 0.177), this difference was not statistically significant. Among ALS patients, those who underwent MRI more than six months after symptom onset had significantly lower SMI values compared to both those who underwent MRI within six months and controls (respectively, p = 0.014, p = 0.018). No significant SMI difference was observed between ALS patients who underwent MRI within six months and controls (p = 0.626).

Conclusion: Cervical SMI measurements at the C3 vertebral level may support ALS diagnosis, particularly in patients with longer disease duration. SMI may also provide insight into early muscle loss due to denervation.

Introduction: Morbidity and mortality related to brain metastases (BM) are affected by their intracranial distribution, consistency (solid vs. cystic), and extent of peritumoral brain edema. We have hypothesized that the vascular properties of the different vascular territories of the brain may influence differences in BM's radiologic morphologies.

Methods: This is a retrospective study of all adult patients (age ≥18 years) with histopathological confirmed BM. Based on radiologic features, the patients were divided into 3 groups: solid, cystic-necrotic, and purely cystic. Data on different variables were extracted for eligible cases and used for statistical-based comparisons between groups.

Results: Following categorization according to radiologic phenotype, 61 (32.3%), 85 (45%), and 43 (22.7%) cases were considered solid, cystic-necrotic, and purely cystic, respectively. On univariate analysis, the purely cystic phenotype was significantly associated with male gender, posterior cerebral circulation, lung cancer (vs. breast cancer), neuroendocrine tumor, and older age. On multivariate analysis, posterior circulation (OR = 8.782, p < 0.001), neuroendocrine tumor (OR = 4.539, p = 0.046) and older age (OR = 1.075, p = 0.021) remained significant. In addition, on multivariate analysis, severe edema was significantly associated with the solid phenotype, anterior circulation and age < 55 years cases.

Conclusion: The two cerebral circulations are significantly associated with different BM radiologic phenotypes as well as with differences in the extent of peri-lesional brain edema. Furthermore, several epidemiological, histological and molecular variables are also associated with these important radiologic features. As our data on factors associated with BM radiologic morphologies grows, so our understanding of the relevant pathophysiology will expand, leading to practical implications affecting morbidity and prognosis.

Background: As a complex condition, spinal cord injury (SCI) has devastating consequences for physical, financial, social, and emotional well-being. After SCI, damage increases due to oxidative stress (OS) and inflammation, mechanisms which have been identified as potential therapeutic targets. Tibolone (TIB), a selective tissue estrogen activity regulator (STEAR), has neuroprotective properties demonstrated in some experimental models.

Objective: We investigated the effect of TIB on OS and inflammation in a rat model of traumatic SCI.Methods: Moderate contusion SCI was produced at thoracic level 9 (T9) in male Sprague Dawley rats. The animals were then divided into groups and received oral doses of TIB (0.1, 1, and 10 mg/kg) at various times (30 minutes, 24, and 48 hours). Animals underwent euthanasia 72 hours after the SCI. Spinal cord tissue and serum samples were collected for the analysis of OS (superoxide dismutase activity (SOD), malondialdehyde (MDA) levels, and protein carbonyl concentration), and inflammation markers (IL-6, IL-1β, and TNFα concentration).

Results: TIB administration significantly increased SOD activity in the spinal cord tissue but not in the serum. In contrast, TIB decreased MDA and carbonyl levels in both samples. Also, TIB decreased pro-inflammatory cytokine levels (IL-6, IL-1β, and TNFα) in the spinal cord tissue and serum.

Conclusions: The best results were observed with the 0.1 mg/kg dose. TIB demonstrated a protective effect by decreasing OS and inflammation after SCI, suggesting an estrogenic effect of this STEAR. However, further studies should be conducted to elucidate the exact mechanism by which TIB exerts neuroprotection after SCI.

Background: Traumatic brain injury (TBI) remains a major public health concern due to its high morbidity and mortality. The 'golden hour' principle suggests that outcomes improve with rapid access to definitive care. However, the role of prehospital transport time in TBI prognosis remains unclear, particularly in resource-limited settings. This study evaluates the relationship between hospital arrival time and functional prognosis in TBI patients.

Methods: A cross-sectional observational study was conducted in two Ecuadorian trauma centers from 2017 to 2020. Patients were categorized into early (<8 h) and late (>8 h) hospital arrival groups. Demographic, clinical, radiological, and surgical variables were analyzed. The primary outcome was functional prognosis, measured by the Glasgow Outcome Scale (GOS) at hospital discharge. Logistic regression was used to adjust for confounding variables.

Results: A total of 373 TBI patients were analyzed. The early-care group presented with more severe injuries, lower Glasgow Coma Scale (GCS) scores, and higher rates of abnormal pupillary responses. Late-arriving patients had better initial neurological status and were more likely to have received prehospital stabilization. Surgical intervention was delayed in both groups, with 67.8% of early-care patients undergoing surgery 8-24 h post-trauma. Adjusted analysis showed no significant difference in functional outcomes between early and late-care groups (OR 1.95, p = 0.08).

Conclusion: Hospital arrival time alone does not significantly influence TBI outcomes. Instead, prehospital stabilization, initial GCS, and timely surgical intervention are stronger prognostic factors. Trauma care strategies should prioritize improving prehospital management and reducing in-hospital delays rather than strictly adhering to the 'golden hour' paradigm.

Objective: Rosemary is a traditional Chinese medicinal herb recognized for its therapeutic potential in cardiovascular and cerebrovascular diseases. Its primary active constituent, carnosic acid, has been shown to reduce infarct volume in ischemic stroke models. However, the mechanisms underlying the effects of rosemary and carnosic acid, and their specific actions in ischemic stroke remain incompletely understood.

Methods: In this study, we evaluated the therapeutic effects of rosemary and carnosic acid using a middle cerebral artery occlusion/reperfusion model, and predicted their mechanisms of action network pharmacology and molecular docking approaches, with key targets subsequently validated using quantitative PCR analysis.

Results: The results showed that both rosemary and carnosic acid significantly reduced infarct volume and improved neurological function. Rosemary treatment increased spleen weight, suggesting a potential immunomodulatory role, whereas carnosic acid had no significant effect on spleen weight. Network pharmacology analysis indicated that rosemary regulated multiple molecular pathways, including the VEGF, PI3K-Akt, and TNF signaling pathways, while carnosic acid primarily influenced pathways associated with apoptosis and inflammation. Molecular docking and qPCR validation further demonstrated that carnosic acid modulated apoptosis through key targets such as TNF-α, TP53, MMP9, and PPARG.

Conclusion: Rosemary and carnosic acid exert neuroprotective effects in cerebral ischemia-reperfusion injury through distinct mechanisms, demonstrating their potential as complementary therapeutic agents for ischemic stroke.